predictive maintenance in the industry 4.0 a systematic literature review

Predictive maintenance in the Industry 4.0: A systematic literature review

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Industry 5.0: A survey on enabling technologies and potential applications

Industry 4.0 ten years on: a bibliometric and systematic review of concepts, sustainability value drivers, and success determinants, predictive maintenance and intelligent sensors in smart factory: review., integration of industry 4.0 technologies into total productive maintenance practices, data science applications for predictive maintenance and materials science in context to industry 4.0, systematic mapping studies in software engineering, industry 4.0: a survey on technologies, applications and open research issues, deep learning for iot big data and streaming analytics: a survey, an introduction to predictive maintenance, recent advances and trends in predictive manufacturing systems in big data environment, related papers (5), trending questions (1).

This paper provides a systematic literature review on predictive maintenance in the context of Industry 4.0, discussing methods, standards, and applications.

Predictive maintenance approaches in industry 4.0: A systematic literature review

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The emergence of Industry 4.0 has heralded notable progress in manufacturing processes, utilizing sophisticated sensing and data analytics technologies to maximize efficiency. A vital component within this model is predictive maintenance, which is instrumental in ensuring the dependability and readiness of production systems. Nonetheless, the heterogeneous characteristics of industrial data present obstacles in realizing effective maintenance decision-making and achieving interoperability among diverse manufacturing systems. This paper addresses these obstacles by introducing a hybrid approach that harnesses the power of ontologies, machine learning techniques, and data mining to identify and predict potential anomalies in manufacturing processes. Our work concentrates on designing an intelligent system with standardized knowledge representation and predictive capacities. By bridging the semantic divide and enhancing interoperability, ontologies enable the amalgamation of various manufacturing systems, thereby optimizing maintenance decision-making in real-time. As demonstrated in the experimental results, this approach not only ensures system reliability but also fosters a seamless, integrated, and efficient production landscape.

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DOI: 10.3390/app12168081
Corpus ID: 251612466

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The influence of predictive maintenance in industry 4.0: A systematic literature review

2022, 2022 2nd International Conference on Innovative Research in Applied Science, Engineering and Technology (IRASET)

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Clustering the Research at the Intersection of Industry 4.0 Technologies, Environmental Sustainability and Circular Economy: Evidence from Literature and Future Research Directions

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Published: 26 June 2024

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Suman Kumar Das ORCID: orcid.org/0000-0002-5145-7727 1 ,
Gianmarco Bressanelli ORCID: orcid.org/0000-0003-2255-9983 1 &
Nicola Saccani ORCID: orcid.org/0000-0002-4603-5060 1

Digital technologies may enable the adoption of Circular Economy models in production and consumption processes, thereby promoting environmental sustainability. Literature on these topics has grown exponentially over the last decades, focusing on the adoption of Industry 4.0 technologies and its implications for environmental sustainability or circularity. However, extant literature reviews failed to cover the vast amount of literature produced, since they either have a narrow scope or focus on a limited sample of articles. To fill this gap, a bibliometric literature review was carried out on a sample of 1002 scientific articles on Circular Economy, Industry 4.0 technologies, and environmental sustainability. Descriptive statistics are coupled with a cluster-based analysis to provide a comprehensive coverage of the broader subject matter. Eight research clusters have been identified, with two general clusters (linkages between Industry 4.0, Circular Economy, environmental sustainability) and six topic-specific clusters (Big Data analytics for supply chain circularity, circular and sustainable additive manufacturing, urban sustainability, sustainable circular and digital (re)manufacturing, blockchain and data integration for a sustainable Circular Economy, miscellaneous and sectorial applications). Clusters are discussed in terms of research themes, methodologies, technologies, and circular strategies. Finally, a research agenda is drafted, pointing out six cluster-specific and four more transversal research directions. Hence, this research offers a detailed and quantitative overview of the research landscape, helping researchers and managers in understanding past contributions, assessing current standings, and identifying future directions of the research at the intersection of Industry 4.0 technologies, environmental sustainability, and Circular Economy.

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Introduction

To address the environmental challenges posed by the current production and consumption model, Circular Economy (CE) posits a new economic system wherein resources are reused, remanufactured, and recycled to create new products and services. In this context, Industry 4.0 (I4.0) technologies can facilitate the implementation of CE strategies and increase environmental sustainability. The amount of scientific literature on CE, I4.0 technologies and environmental sustainability has grown exponentially in recent years. Previous studies have linked I4.0 with the CE. For instance, a comprehensive theoretical and practical review has been conducted on the smart circular economy (CE) paradigm, explicitly linking the technical mechanisms of I4.0 technologies with CE operational strategies [ 1 ]. Further discussions have explored the design and implementation of circular manufacturing processes, emphasizing the integration of CE with I4.0 technologies [ 2 , 3 ]. Previous literature has also investigated the linkages between I4.0 and sustainability, specifically focusing on sustainability performances, sustainability practices, and the influence of several moderating factors [ 4 , 5 ]. Similarly, earlier literature studied the linkages between CE and sustainability, examining similarities and differences and their interrelationships at micro, meso, and macro levels [ 6 , 7 ]. However, previous reviews in the field of CE, I4.0 and environmental sustainability have focused either on a limited number of papers or have a narrow scope, addressing specific aspects or technologies such as circular or sustainable business models, organizational barriers, and enablers for CE and sustainability implementation, without providing comprehensive coverage [ 8 , 9 , 10 ]. Therefore, the objective of this paper is to structure the vast amount of literature dealing with I4.0 technologies and CE or environmental sustainability, to identify how these knowledge streams have developed. The aim is to identify the main research themes and topics investigated, as well as to spot research gaps and define future research directions. Given the vast number of articles that have been written on these topics, a bibliometric review approach has been employed to achieve the research objective. Bibliometric literature reviews are a powerful tool for monitoring the evolutionary progress within a research field. This is achieved by analyzing the underlying structures and connections between different topics using the bibliographic coupling technique. This approach allowed to identify emerging thematic clusters within the field and determine a set of future research direction. The remainder of the paper is structured as follows. The next Section provides the background and explains the motivation of this study. Then, the methodology is outlined in the subsequent Section. Descriptive statistics are presented in the fourth Section, while bibliometric network and cluster analysis are reported in the fifth Section. Section 6 elaborates a list of future research directions. Lastly, the final Section concludes the review by summarizing key findings and their implications for the field.

Theoretical Background

Environmental sustainability, circular economy, and industry 4.0 technologies.

The concept of sustainability is defined by the Brundtland commission [ 11 ] as a “ development that meets the need of the present without compromising the ability of future generations to meet their own needs ”. Within the broad domain of sustainability, the focus of this research has been narrowed down to environmental sustainability. This aspect emphasizes the importance of maintaining ecological balance and minimizing environmental impact by reducing resource consumption and waste generation across the entire supply chain [ 11 ]. In this context, CE is an economic model based on a restorative and regenerative approach, which aims to minimize resource input, waste generation, and energy leakage by slowing, closing, and narrowing material and energy loops, thereby replacing the end-of-life concept with the principles of reduce, reuse, and recycle [ 12 , 13 , 14 , 15 ]. It involves the reengineering of many aspects of production and consumption systems to separate ecological activity from resource depletion.

Scientific literature recognizes I4.0 technologies as enablers for the transition towards CE to achieve environmental sustainability. Broadly speaking, I4.0 can be seen as a paradigm shift that involves the digital transformation of industrial value chains, connecting different physical devices that continuously interact and exchange information not only between machines but also between humans. Several technologies are often included under the I4.0 umbrella, although their classification is challenging due to different perspectives adopted by scholars in various disciplines [ 16 ]. These technologies are transforming production and consumption systems, enabling companies to increase efficiency and reduce costs. One of the most mentioned I4.0 technologies is Internet of Things (IoT), a network of connected devices that communicate with each other and share data. IoT can be used to track and optimize resource usage, reduce waste, and enhance energy efficiency [ 17 ]. Big Data analytics, instead, refers to the storage, analysis, and interpretation of large and complex data sets. Big Data analytics provide insights into resource usage and product lifecycles, enabling companies to identify opportunities for resource optimization and circular practices development [ 18 ]. For example, the analysis of errors and failures during product usage can enhance green product development practices. Additive manufacturing based on 3D Printing allows for the creation of complex and customized products, reducing scraps and enabling local production [ 19 ]. This technology can also reduce the need for transportation and storage of goods, further enhancing environmental sustainability. It also supports the creation of closed-loop systems by allowing the use of recycled materials within manufacturing processes [ 20 ]. Blockchain is a secure and decentralized system for recording transactions. It can be used to track supply chain activities, improving traceability, ensuring product authenticity, and enhancing the transparency and security of goods [ 21 ]. Cyber-physical systems integrate physical and virtual components to monitor and control manufacturing processes. This technology can optimize resource usage and enable more efficient and precise manufacturing processes to minimize waste through the monitoring of physical processes [ 22 ]. Cloud Computing allows the storage and analysis of massive amounts of data on remote servers. This technology can reduce the need for on-premises infrastructure such as computer hardware and enable the creation of virtualized environments that can be easily duplicated and shared [ 23 ]. This technology also enables on-demand use of information required by manufacturing, which enhances the processing capability of information and thus improves production efficiency [ 24 ]. Augmented Reality enhances the real world with digital information through the combination of real and virtual worlds, resulting in new environments for visualizations where physical and digital objects coexist and interact in real time. This technology facilitates the provision of maintenance and repair activities, reducing downtime and improving workers’ safety [ 25 ]. Lastly, industrial robotics encompasses the deployment of robots in industrial environments for the purpose of automating tasks, enhancing efficiency, productivity, flexibility, to facilitate interactions with other machines, and ensuring safe collaboration with humans [ 26 ]. It can help strengthen CE by increasing efficiency and precision in sorting and disassembling materials for remanufacturing and recycling, thus reducing unsorted waste and promoting resource conservation [ 27 ].

Research Gaps and Motivations for this Research

To establish the research context, a preliminary analysis of previous literature reviews on CE, I4.0 technologies, and environmental sustainability has been conducted. As shown in Table 1 , many existing reviews have a narrow scope compared to the objectives of this research, since they limit their focus on specific CE or sustainability aspects. For instance, Ejsmont et al. [ 5 ] explored the relationship between sustainability and I4.0 without addressing CE. Similarly, Korner et al. [ 8 ] concentrated only on a specific technology (additive manufacturing). Montag [ 10 ] studied sustainability, supply chain management and CE without including I4.0 in the search strings, although the application of I4.0 technologies in circular supply was suggested by the authors for future research. Heittarachchi et al. [ 20 ] focused only on quantitative methods adopted for investigating sustainable supply chains, and Olivera Neto et al. [ 28 ] narrowed down their discussion to the implementation of eco-efficiency tools. Khan et al. [ 29 ] carried out a thorough content-based analysis, although specifically focusing only on sustainable business models. In other cases, CE or environmental sustainability have been treated only as side or marginal topics in the discussion of results [ 16 , 30 , 31 ].

Therefore, this research expands upon these existing studies in multiple aspects, attempting to fill their limitations on: (i.) the lack of a simultaneous integration of CE, environmental sustainability, and I4.0 perspectives; (ii.) the limited scope of research and the tendency to focus only on specialized investigations (such as specific technologies, specific methods, or specific aspects), rather than providing a comprehensive coverage of the broader subject matter; and (iii.) the relatively small number of articles analyzed (with the notable exceptions of [ 7 , 16 , 31 ]), which limits the breadth and depth of the research. This research, indeed, aims to analyze the vast amount of literature that touched the connections among Industry 4.0 technologies, CE and environmental sustainability and understand their linkages at the broader level, as well as their interrelation mechanisms and under investigated research areas.

Materials and Method

Bibliometric analysis is a well-established and widely recognized literature review method, allowing to analyze and summarize large sets of articles while encouraging the generation of novel research concepts. It uses mathematical and statistical techniques to evaluate large quantities of bibliographic information [ 34 ]. This technique measures the interaction of various bibliographic information using widely accepted academic indicators such as the total number of publications, the number of citations received, h-index, and so on [ 35 ]. This study adopted two distinct forms of bibliometric analysis. The first one (‘research performance assessment’), examines descriptive characteristics such as country, institutions, journals, and articles distributions within a specific research domain. The second one (‘science mapping assessment’) identifies the pattern of progression, intellectual structure, and dynamic evolution of research fields in a specific area [ 36 , 37 ].

Literature Search, Identification, Screening, and Inclusion

The PRISMA framework is employed for the systematic identification, screening, eligibility assessment, and inclusion of relevant literature [ 38 ]. A comprehensive overview of the process utilizing the PRISMA approach is outlined in Fig. 1 , depicting the number of articles identified at each successive step.

Flow diagram for the selection of literature reviewed based on PRISMA

First, relevant studies are identified through Scopus. A Boolean search was conducted on ‘title-abstract-keywords’ based on two group of keywords. The first group focused on ‘Industry 4.0 technologies’ and ‘Digital Technologies’ and included terms such as ‘Internet of things’, ‘Cyber physical system’, ‘Cloud computing’, ‘Industrial robotics’, ‘Data analytics’, ‘Big Data’, ‘Additive manufacturing’, ‘3D printing’, and ‘Industry 4.0’. The second group of keywords was derived from ‘Circular Economy’ and ‘Sustainability’. The search query led to extraction of 7732 records.

Then, a screening process was conducted to ensure the quality of the records. Authors excluded articles written in languages other than English. The results were further refined by focusing on scientific papers and restricting the selection to peer-reviewed journal articles and review papers, thus excluding books and conferences. Then, after narrowing down the subject area to engineering, business management, operations, services, manufacturing, decision science, interdisciplinary studies, and environmental science, a total of 3333 studies was selected.

Then, titles and abstracts were checked based on three inclusion criteria:

The article must have a strict or specific focus on I4.0 technologies, digital technologies, or Industry 4.0, rather than discussing these topics in general terms.

The article must have a strict or specific focus on CE or environmental sustainability, rather than discussing these topics in general terms or merely acknowledging sustainability or CE as a relevant trend or theme.

The article must focus on the technical side of the Ellen MacArthur Foundation’s Butterfly Diagram [ 12 ]. This side aims to retain the value of technical products, components, and materials at the highest value, encompassing processes such as reuse, repair, remanufacturing, and recycling.

The articles that matched all three of these criteria were chosen for further study. The final set includes 1002 articles.t

Descriptive, Bibliometric, and Thematic Analyses

The total of 1002 articles have been analyzed utilizing bibliometric analytic tools and techniques. All bibliographic information, including abstracts, keywords, citation details, funding information, and other relevant data, was recorded and exported in a.csv format. A MS Excel database was created to maintain and organize the data throughout the review process and facilitate quantitative evaluation of each article. The data was reviewed by two different authors for collaborative re-examination of the papers, aiming to track disagreements and verify the analysis. Biblioshiny, an R-based bibliometric software that accepts BibTeX or plain text format input from Scopus, was used for bibliometric analysis. This software offers statistical analysis and data visualization tools. To visualize and analyze the database, the authors employed VOS viewer [ 39 ], widely used in bibliometric analysis studies [ 16 ]. These tools are known for their reliability, replicability, and user-friendly nature, enabling the analysis to be reported accurately and consistently and yielding consistent results.

The fourth Section involves bibliometric analysis based on the descriptive statistical assessment of the database. The fifth Section, instead, discusses bibliometric networks and cluster analysis based on the bibliographic coupling method featured in VOS viewer. Bibliographic coupling is a science mapping methodology that analyses the similarities between two publications based on the number of shared references. This approach works on the idea that two publications that share references are also similar in content. This methodology is best applied within the same or a specific time-period and in the field of management [ 39 ], as it presents emerging literature and research fronts more accurately than co-citation analysis [ 36 ]. By analyzing the bibliographic coupling network of documents, underlying structures and connections between different topics or research areas can be revealed, thus creating thematic clusters [ 40 ]. The bibliographic information of 1002 articles were inputted into VOS viewer, and a bibliographic coupling analysis with documents was conducted using the fractional counting method. The minimum number of citations was kept to zero to give each publication the same weight regardless of the number of citations it has received. In fact, being very recent, many articles in the sample have few or no citations. Articles that had almost no bibliographic linkage with others have been removed [ 41 ]. As a result, the VOS viewer developed a network for 833 remaining documents, identifying eight clusters of connected articles where each paper has been assigned to only one cluster. Using thematic analysis, significant differences in the subject matter were identified among clusters. Title and keyword analysis identified all relevant papers within each cluster. Given the large number of articles, the top ten most influential articles in each cluster, based on total link strength and citation value, were chosen for a more in-depth thematic analysis. This approach has been followed several times in bibliometric literature reviews [ 42 ]. Various dimensions have been analyzed to delve deeper into the literature and extract meaningful information, such as articles’ objectives, methodologies, CE strategies, and I4.0 technologies investigated [ 43 ]. The thematic analysis was also employed to define the research agenda. An analysis of the clusters revealed suggested research directions. From these, common and specific future research topics were identified.

Research Performance Assessment: Descriptive Results

This section presents the results of the research performance analysis, describing the temporal distribution of articles, the contributions of different countries, and leading journals. Figure 2 depicts the temporal distribution of the 1002 articles analysed, which spans between 2010 and 2022. The number of articles published have raised strongly over time, reaching 349 in 2022. This confirms that, over the last decade, there has been an exponentially growing interest in the research on CE, environmental sustainability and I4.0 technologies.

Number of articles published by year

The geographic distribution of research is determined based on the corresponding author's affiliation. Since research articles are frequently co-authored by researchers from various countries, affiliation provides a more accurate representation of the research location compared to authors’ nationality, as used in other literature reviews [ 44 ]. Table 2 shows the ten most active countries. The top ten countries account for more than the half of the papers in the sample (52%). China, being the most productive country, accounts for the 11% of the articles, followed by India and Italy (both close to 8%), UK, and USA. The geographical analysis of publications indicates that most active countries can be divided into two groups: western industrial economies (such as Italy, UK, USA, Germany, France, and Spain), and developing economies with large consumer societies (China, India, and Brazil). France has the highest average number of citations per publication (55.4), followed by China (48.2) and Germany (47.4). The Table shows the patterns of contributions and collaborations among countries through the Single Country Publications (SCP) and Multi-Country Publications (MCP) indexes. MCP indicates the number of articles that have at least one author who comes from a country different from the corresponding author, whereas SCP indicates the number of articles where all the authors are located in the same country. China leads also in the number of MCP (60), followed by UK (36), India (33) and Italy (24).

The 1002 studies have been published in 301 different academic journals. Among them, only eight journals published fifteen or more articles related to CE, environmental sustainability, and I4.0 technologies. They are Sustainability (223), Journal of Cleaner Production (107), Energies (21), Business Strategy and the Environment (20), International Journal of Advanced Manufacturing Technology (19), Resources, Conservation and Recycling (17), Production Planning and Control (16), and International Journal of Production Research (16). These journals cover altogether 43% of the total sample. Regarding total citations, the Journal of Cleaner Production achieved most citations (6176), followed by Sustainability (5080) and International Journal of Advanced Manufacturing Technology (2719). The latter, however, leads as the journal with the maximum average citations per article (143.1), followed by International Journal of Production Research (94.6), Resources, Conservation and Recycling (74.0), International Journal of Production Economics (64.0), and Journal of Cleaner Production (57.7) (as shown in Table 3 ).

Science Mapping Assessment: Cluster Analysis

A cluster analysis based on the bibliographic coupling method was carried out using VOS viewer. Eight clusters were identified. Table 4 describes them, including their primary research topics and their dimension measured as the number of articles contained in each cluster. It also provides a visual representation of each cluster. Cluster 1 is the largest while Cluster 8 is the smallest. Cluster 7 covers the longest time span, with the earliest articles from 2011. The main topics, methodological aspects and research gaps of the clusters are briefly described hereafter. The supplementary material includes the categorization and allocation of the 1002 articles into clusters.

Cluster 1: General Linkages Between Sustainability and Industry 4.0 Topics

Cluster 1 is the largest (170 publications) and has a focus on general aspects about sustainability and I4.0. It discusses primarily the enabling role of I4.0 technologies for sustainability, their relationship to sustainable development, and their impact on environmental, economic, and social performances, but with no specific reference to CE. The papers in the cluster adopt various methodologies such as systematic literature reviews and framework conceptualization, often resorting to expert-based opinions. In fact, the articles in this cluster focused on exploratory research, mainly adopting qualitative approaches, and focusing on the development of conceptual frameworks. Expert based opinion methods are used to prioritize, categorize, ranks, and identify the relationship between different constructs [ 4 , 9 , 45 ]. For example, Ghobakhloo M. [ 27 ] found different functions of I4.0 technologies that contribute to sustainability and, through expert-based opinions, established contextual relationships between pairs of factors. Similarly, Nara et al.[ 9 ] conducted a systematic literature to find different key performance indicators, grouped them based on experts’ opinion, and validated them with a survey on 72 technical specialists and managers. At a more general level, the papers in this cluster highlight that I4.0 can significantly contribute to sustainable development through resource efficiency enhancement, waste reduction, and product design improvement. For example, Felsberger & Reine [ 46 ] investigated the effectiveness of I4.0 technologies such as smart factory technologies, data-driven technologies, and shop floor equipment technologies for different sustainability dimensions. El Baz j et al.[ 45 ] evaluated empirically the various sustainability drivers that influence the adoption of I4.0 technology and emphasised the importance of management support. Challenges related to the adoption of I4.0 technologies for achieving sustainability are also highlighted throughout the cluster. They include the high cost of implementing I4.0 technologies and the scarcity of expertise and skills needed for the implementation and management of these technologies. Additionally, challenges in the social dimension such as income and employment polarisation resulting from I4.0 have been highlighted [ 47 ]. Challenges about data privacy and security are also notable and requires an evaluation of the effectiveness of government policies [ 4 ]. Besides practical implementation challenges, several opportunities for future research arise from this cluster. From an organizational perspective, a promising future research direction involves investigating the application of I4.0 technologies to improve personalized information and knowledge management [ 27 , 46 ]. In addition, investigating how sustainability can drive the adoption of I4.0 technologies would be also highly relevant [ 4 ].

Cluster 2: General Linkages Between Circular Economy and Industry 4.0 Topics

Cluster 2 (104 publications) focuses on digitization in relation to CE and circular business models. The papers included in this cluster cover a vast range of topics, such as the role of digitalization in enhancing productive maintenance in manufacturing firms [ 48 ], circular business models [ 21 ], and circular supply chains [ 24 , 49 ]. In general, research in this cluster develops frameworks to connect different constructs often based on systematic literature reviews. For instance, Gebhardt et al. [ 49 ] created a framework for the collaboration mechanisms enabled by I4.0 technology, focusing on IoT, Big Data analytics, and cloud computing as enablers of circularity in supply chains. Salvador et al. [ 21 ] investigated digital technologies to enable circular strategies such as design for circularity and their impact on business models. Liu et al.[ 50 ] investigated digital technologies to facilitate the integration of different Reduce, Reuse, Repair, Repurpose, Remanufacturing, Recycle, and Recover strategies [ 51 ]. Hence, I4.0 technologies such as IoT and cloud computing have been proven to be effective enablers of specific CE practices such as product life extension, reuse, and recycling. Some papers explored the challenges related to policy, technology, and behavioral change as well as the opportunities in implementing CE practices [ 52 ], while others aimed to develop conceptual frameworks or value chains designs to achieve circularity. Moreover, some of the articles highlighted the complexity behind a successful implementation of I4.0 technologies due to high cost and high financial risks. This, in turn, create a digital divide with some companies being able to adopt circular practices using expensive I4.0 technologies while others are left behind due to financial constraints and a lack of resources [ 53 ]. Overall, research articles in this cluster generally adopt a theoretical perspective. Therefore, more empirical studies are often suggested. Further investigation into the creation of collaborative platforms and systematic collaboration methods to connect different stakeholders involved in circular supply chains can be considered as a valuable future research direction in this cluster. Moreover, theories are needed to synthesize specific technologies and their interconnection in the context of CE [ 49 , 54 ]. Lastly, studying various circular business model building blocks (such as consumer segments, value propositions, channels, consumer relationships, etc.) in specific manufacturing industries would be an intriguing area of research [ 21 , 54 ].

Cluster 3: Industry 4.0 and Big Data Analytics for Supply Chain Circularity and Sustainability

Cluster 3 (96 publications) focuses on the relationship between I4.0 technologies and sustainable, circular supply chain initiatives. This cluster is therefore more specific than Clusters 1 and 2, focusing on supply chain management and emphasizing the role of Big Data analytics among the wide I4.0 technologies umbrella. The studies in this cluster shed light on the crucial role of digital technologies and advanced analytics in fostering sustainable supply chains, enhancing resilience, and enabling reverse logistics. They explore the intersection of supply chain management, I4.0 technologies (with particular to Big Data analytics), and CE strategies, drawing on diverse industries, geographical regions, and data sources. Interestingly, different papers in this cluster employ empirical methods, both quantitative and qualitative. Some of the research papers utilize surveys to test hypotheses in different geographical regions. For instance, Di Maria et al. [ 55 ] focus on the mediating role of supply chain integration in the correlation between I4.0 technologies and CE practices. Based on a survey of 1200 Italian firms, they found that supply chain integration plays a crucial role in realizing the potential benefits of I4.0 technologies in achieving circularity in supply chains. Akbari & Hopkins et al. [ 56 ] explored how digital technologies can enable supply chain sustainability in emerging economies by surveying 223 Vietnamese supply chain experts. Overall, the study emphasizes the importance of the interplay among sustainable supply chain management, CE practices and I4.0 technologies. The authors emphasize the importance of adopting a holistic and integrated approach to smart sustainable supply chain management that addresses supply chain disruption, supply chain capability development by enhancing flexibility and effectiveness, and resource recovery frameworks for low-cost material collection by improving environmental, social, and economic dimensions [ 57 ]. According to this cluster, reverse logistics is frequently neglected by manufacturing companies compared to forward supply chains due to operational challenges, knowledge gaps related to circular supply chains and smart technologies, low return on investment, a lack of support from top management and technological challenges [ 58 , 59 ]. Therefore, it is suggested that future research should address these technological barriers such as data inadequacy, information structure due to different digital formats, a lack of industrial competency and expertise, and challenges in the implementation of innovative devices and information technology [ 57 ]. A focus should be placed on the government's role in assessing the effectiveness of implementing environmental taxation waiver schemes as well as developing regulations and policies to encourage firms to adopt waste disposal strategies within a circular supply chain network [ 60 ]. Researching data-driven approaches to measure and monitor supply chain sustainability performance, as well as evaluating sustainable outcomes, presents an intriguing area of study [ 20 ].

Cluster 4: Additive Manufacturing for Circularity and Sustainability

Cluster 4 (140 publications) focuses on additive manufacturing and 3D Printing as a technology allowing to minimize waste, optimize resource consumption, and promote circularity in the manufacturing industry. The articles in this cluster discuss the relationship between life cycle sustainability and additive manufacturing, providing frameworks for sustainability assessment and proposing strategies for optimizing the process for eco-effective production systems [ 61 ]. Topics addressed include the sustainability assessment of additive manufacturing, the design of distributed recycling via additive manufacturing [ 62 ], the integration of additive manufacturing and CE [ 33 ], and the impact of additive manufacturing on business models [ 63 ]. Several papers adopted a systematic literature review approach to condense and assess the current literature in the field. Interestingly, some papers in the cluster use analytical methods and statistical analyses to evaluate additive manufacturing parameters. For instance, Mele & Campana [ 64 ] proposed an adaptive slicing method for liquid crystal display 3D printing, which can reduce waste and energy consumption. Although several papers focus on reuse and recycling [ 61 , 62 ], reduce is also a referenced CE strategy [ 64 ]. Articles highlight some of the potential benefits of additive manufacturing for circular product design [ 61 ], and sustainable business models [ 8 ], including operational and economic benefits related to reduced material waste, lower transportation costs [ 65 ], and the ability to offer consumer-centric customization [ 63 ]. A reduction in inventory is also possible through on-demand production. Additionally, another advantage of localized production is the potential to shorten the supply chain while improving environmental and social benefits [ 62 ]. However, there is a need to develop a reverse logistic framework to successfully implement additive manufacturing by connecting different supply chain actors. Furthermore, more empirical research is needed to understand how additive manufacturing initiatives are perceived at the social level. Both active participation and supportive policies of governments and policymakers need to be addressed to increase the adoption rate of additive manufacturing for sustainability and circularity purposes. A potential future direction is to investigate innovative additive manufacturing methods and strategies for preparing and using recycled materials as input feedstock, develop standardized indicators for assessing environmental impacts to produce additive manufacturing feedstock, and optimize energy and material-efficient production processes through methods like distributed recycling, polymerization, and laser cladding [ 62 , 63 ].

Cluster 5: Urban Sustainability

Cluster 5 (119 publications) primarily revolves around the theme of urban sustainability, including the literature on data driven smart sustainable cities, ICT infrastructure for urban sustainability, and digital technologies in the context of smart cities. In the context of urban development, the integration of I4.0 technologies such as IoT, Big Data and cloud computing play a significant role in enhancing waste management and environmental sustainability. Wu et al. [ 31 ] focused on the collection and analysis of real-time data from digital instruments placed in urban environments. These enabling technologies contribute to the so-called data-driven smart cities [ 66 ], and their ICT infrastructures support data-driven decision-making to achieve urban sustainability and empower urban intelligence. Additionally, authors frequently discussed the potential risks, benefits, and ambidexterity capabilities (to achieve both innovation and efficiency) to fulfil the current business demand as well as future perspective. Challenges surrounding the adoption and implementation of digital technologies are also discussed. Some paper highlights the importance of citizen engagement and empowerment in the design and implementation of smart cities [ 67 ], while others emphasize the need for policies and regulations that balance innovation and sustainability [ 68 ]. However, the role of government in establishing political mechanisms and policy measures for smart cities still needs to be further explored. For instance, the prototype developed for the Stockholm Royal Seaport (SRC) uses a hybrid Smart Urban Metabolism approach to achieve sustainability through robust environmental policies, combining various methods and technologies to create a comprehensive solution for monitoring and analysing environmental sustainability aspects [ 67 ]. Additionally, greater attention should be given to social acceptability and the impact of adopting urban sustainability strategies. To create more efficient and sustainable cities, further research is needed on urban intelligence. This refers to a city's ability to harness real-time data and optimize interconnected systems like energy distribution, water distribution, waste collection, and communication networks. In addition to urban intelligence, research should explore resilient data-driven decision-making. This incorporates data acquisition from multiple sources, data stream management, and integration of diverse urban data to ensure effective decision making. This entails the development of frameworks, protocols, and methods for integrating sensor data into a standardized and structured format to facilitate more efficient analysis, while properly considering data privacy and security concerns.

Cluster 6: Sustainable, Circular and Digital (Re)Manufacturing

Cluster 6 (87 publications) focuses on the integration of sustainable principles, digital technologies and CE aspects in manufacturing and especially remanufacturing operations. Articles in this cluster investigate the role of digital technologies for achieving a sustainable and circular (re)manufacturing. Chau et al. [ 69 ] discussed the prospects for IoT-based technologies in remanufacturing process. Kerin & Pham [ 70 ] explored the use of I4.0 technologies in remanufacturing, particularly in smart remanufacturing environments. Chauhan et al. [ 71 ] proposed a framework for integrating I4.0 and CE principles to analyze and optimize resource consumption in the manufacturing industry. Lopes de Sousa Jabbour et al. [ 72 ] proposed a research agenda and roadmap for sustainable operations that incorporates I4.0 and CE principles for adopting sustainable operations management. According to this cluster, the efficiency and effectiveness of remanufacturing processes can be enhanced by digital technologies such as artificial intelligence, machine learning, and IoT, thus enabling real-time monitoring and optimization of energy consumption. Furthermore, significant resource savings and environmental benefits can be achieved through additive manufacturing. Investigating the role of governments in overcoming barriers and fostering new markets for remanufactured goods, along with the development of supportive infrastructure plans, presents an intriguing avenue for future research. From a knowledge perspective, studying data-driven frameworks that integrate smart circular strategies holds promise in providing extensive product and process information, underscoring the need for effective mechanisms for data quality control and data security. Future research could focus on identifying the barriers to the adoption of I4.0 technologies and exploring skill development, transfer, and trust-building strategies among employees to overcome them [ 72 ]. Additionally, further investigation should advance the understanding of the relationship between dynamic capabilities and the adoption of CE practices in response to changing environmental and market conditions [ 70 ].

Cluster 7: Blockchain and Data Integration for Sustainability and Circular Economy

Cluster 7 (86 publications) discusses Blockchain and data integration for sustainability and CE. The use of blockchain technology in CE practices is a key focus of this cluster, with some papers using empirical findings to develop hypotheses for understanding the impact on sustainable operations. For instance, Rajput and Singh [ 73 ] used a qualitative methodology to collect data through a literature review and case studies, examining the role of artificial intelligence, Big Data analytics, Blockchain, and IoT in CE strategies such as reducing waste and design for circularity. Zhang et al. [ 74 ] developed a framework for implementing blockchain-based life cycle assessments based on a systematic literature review. Other authors identified critical success factors for implementing a blockchain-based circular supply chain, including a shared vision among stakeholders and the ability to adapt to changing technological and regulatory environments [ 75 ]. Umar et al. [ 76 ] presented an empirical study on I4.0 technologies and green supply chain practices, using a quantitative approach with a survey questionnaire as the primary data collection tool. Similarly, the articles explored the potential of integrating blockchain with IoT and RFID to enhance sustainability in distribution and order management. Among these technologies, blockchain stands out due to its features such as immutability, transparency, reliability, and verifiability, making it an ideal solution for facilitating information flows among complex supply chain networks and stakeholders. Additionally, the papers highlight the importance of critical success factors for implementing blockchain-based circular supply chains, such as trust, transparency, and data privacy [ 73 , 74 , 75 ]. In line with other clusters, future research can expand the empirical studies by investigating the sustainability practices facilitated by blockchain-based solutions. There is a need for exploring the social impact of I4.0 on human resource management practices and examining the relationship between adoption rates and technical knowledge constraints. More attention needs to be given to the role of government policies and regulations in promoting the adoption of blockchain and I4.0 technologies. Another important aspect concerns enhancing data traceability, security, and integrity features of blockchain use for smart contracts. This improvement can contribute to building trust between partners and to fostering collaborative relationships [ 74 , 75 ].

Cluster 8: Miscellaneous and Sectorial Applications

This cluster (31 publications) delves into industry-specific applications and other miscellaneous topics related to CE and sustainability. It includes 32 papers, making it the smallest cluster. The papers investigate various facets of I4.0 and CE implementation in different industrial contexts. For instance, Abdul-Hamid et al. [ 77 ] scrutinized the drivers of I4.0 in the palm oil industry in Malaysia, while Piyathanavong et al. [ 77 ] examined the role of project management in sustainable supply chain development in the Thai metals industry. Other papers focus on specific industrial applications of CE and I4.0 technologies. Vimal et al. [ 78 ] analyzed the drivers for the adoption of I4.0 technologies in a circular sharing network for paper, cement, and sugar. This cluster emphasizes the importance of empirical research to explore and assess the impact of I4.0 technologies on CE strategies, including the identification of key factors that facilitate successful implementation. For instance, integrated data management systems can significantly enhance collaboration for optimized procurement and production across industries. Additionally, exploring the impact of management systems in mitigating employee resistance to change is suggested as an intriguing avenue for further investigation.

Research Agenda

The influential articles identified through bibliographic coupling analysis and the gaps they point out have been considered as the basis for the development of a research agenda, consisting of ten main research directions. Table 5 connects each identified research direction to the clusters in which it emerged. Research directions are then described in the following. The first four research directions are highly transversal, appearing in at least five clusters, so they are described with more details. Three research directions are common to two clusters, while three have been suggested by one single cluster.

First, an important gap highlighted by the literature concerns the need to move beyond conceptual papers and embrace empirical investigations to gain a deeper understanding and move towards theory-testing research of the relationship between I4.0, environmental sustainability, and CE at both conceptual and practical levels. Furthermore, empirical studies are necessary to address the development and configuration of effective business models and digital manufacturing ecosystems that foster sustainability [ 54 ]. Hence, six clusters emphasised the need for empirical research to investigate and quantify the impact on sustainability and CE as well as to develop indicators assessing economic, environmental, and social impacts [ 4 ]. Empirical evidence would help to fully understand the positive and negative effects of I4.0 adoption for CE and sustainability such as rebound effects.

Research direction #1

To carry out empirical and quantitative research at the intersection of Industry 4.0, environmental sustainability, and Circular Economy.

Seven out of eight research clusters emphasized the importance of addressing the social implications of I4.0 adoption in the context of CE and environmental sustainability. There is a lack of comprehensive investigations into the changes occurring in the current social platform setting, such as education and skills and wealth disparities in consumer markets, which strongly motivates future research. One key aspect emphasized is the effect of automation on low- to middle-skilled jobs [ 63 ]. On the other hand, the creation of new opportunities in technology and engineering fields also deserves further investigation [ 53 ] The importance of addressing income and employment polarization should also be mentioned [ 27 ]. It is vital to ensure social inclusion, citizen participation, and equitable access to sustainable urban development. Atif et al. [ 79 ] suggest exploring the social acceptability of CE products and services as an area for investigation. Additionally, the social aspect of sustainability in supply chain management requires increased attention, with the adoption of reliable social performance measurement models like the social return on investment (S-ROI) [ 73 , 80 ]. Policymakers have a pivotal role to play in promoting the adoption of emerging technologies and fostering skill development [ 74 ]. Research should finally delve into the role of social media in influencing consumer behavior and improving sustainable supply chains.

Research direction #2

To Investigate the social impact of Industry 4.0 technologies adopted for Circular Economy and sustainability.

Government regulations and policies play an important role in enhancing sustainability and CE, as well as the adoption of I4.0 technologies. Government policies and initiatives directly influence several industry aspects, such as market creation, production and logistics as well as engaging different stakeholders at the micro, meso, and macro levels [ 69 ]. It is important to investigate the effectiveness of policy interventions such as subsidies and energy saving regulations that promote sustainable practices, also to minimize socio-economic inequality in reference to I4.0 technologies [ 71 ]. Another aspect to be addressed concerns the environmental impact of the implementation of I4.0. Additionally, given the heavy reliance of I4.0 on data-driven technologies, policies need to address concerns related to data privacy, security, and governance, e.g., safeguarding data, protecting intellectual property rights, and developing regulations for data sharing [ 24 ]. Furthermore, governments have a critical role to play in promoting sustainability among consumers in urban areas: future research should focus on investigating innovative policy measures, monitoring policy effectiveness, and understanding the involvement of stakeholders in the development and implementation of urban sustainability policies [ 81 ]. Moreover, to promote CE practices, policymakers can incentivize the adoption of circular supply networks and green products and provide support to remanufacturing industries [ 76 ]. Finally, cross-national studies can provide valuable insights into different policy-making approaches, enabling policymakers to enhance their strategies and create new markets for sustainable products.

Research direction #3

To investigate the role of government regulations and policies in improving the effectiveness of I4.0 adoption for CE and Sustainability.

Addressing gaps and challenges in data management and integration should be a priority for future research. For instance, the integration of new technologies and the resolution of compatibility issues within existing systems in circular procurement and supply chain management should be addressed. Additionally, ensuring data accuracy, timeliness, and completeness hold significant importance in developing data-driven circular strategies in manufacturing. Research should address challenges associated with developing blockchain-based data management systems, including data manipulation, integration, scalability, and transmission [ 20 , 59 ]. It is essential to enhance data traceability, security, and integrity in blockchain utilization to foster trust and collaborative relationships. Researchers can also concentrate on developing data-driven frameworks that promote semantic interoperability between machines, designing efficient interfaces and data networks to encourage stakeholder collaboration Moreover, fostering knowledge management by enhancing the collection, storage, and sharing of information generated through I4.0 technologies within an organization could significantly contribute to digital supply chain network. In the realm of urban sustainability, there is a requirement to integrate data sources and technologies for effective decision-making in smart cities. This involves developing frameworks, protocols, and applications for the collection and analysis of sensor data, optimizing ICT infrastructure, and for the exploitation of the potential of Big Data and cloud computing [ 68 ].

Research direction #4

To develop frameworks and methods for Data Management and Data Integration for sustainability and Circular Economy purpose.

Moreover, further attention needs to be given to data and cyber security due to the involvement of large data transactions and sharing in I4.0. This is crucial because cyber threats from anonymous user can be challenging to identify, yet they can significantly impact operations and pose challenges [ 16 ]. Additionally, there are opportunities for a more transparent and traceable option using encrypted digital records in the context of manufacturing sustainability. Future research should focus on leveraging digitization to respond to security and privacy concerns in the smart city and manufacturing environments, addressing security threats across different layers of data technologies, and investigating the security and safety of digital infrastructure for citizens, vendors, and stakeholders [ 73 ].

Research direction #5

To address data and Cyber Security issues in the context of Industry 4.0, Circular Economy, and environmental sustainability.

The role of specific I4.0 technologies in decision-making solutions that support planning, control, execution, business model innovation, corporate competitiveness, and on-the-job training capabilities, within the CE paradigm for environmental sustainability has not been thoroughly investigated. While some specific technologies such as IoT and Big Data have been extensively explored, the specific contribution of other I4.0 technologies has been neglected. Given that CE implementation is relatively new, it is crucial to explore the interconnection between different technologies and their role in establishing a CE paradigm [ 57 ]. Additionally, classification frameworks or theories could point out the roles of specific technologies, also acting as prescriptive conceptual tools to support practitioners within the CE context.

Research direction #6

To delve deep into the impact of specific Industry 4.0 technologies on Circular Economy and environmental sustainability.

Clusters 2 and 5 found that future research should explore the development of novel business models and value propositions and the redesign of current business models to prioritize environmental sustainability, in urban settings as well as for different types of manufacturing industries [ 54 ]. As an example, investigations into new business models for streamlining waste management, recycling, and collaboration among local actors in the urban environment are needed [ 82 ]. Additionally, studies should focus on developing new business models for data collection and processing of urban data and solid waste materials management, potentially utilizing emerging technologies such as blockchain or Big Data analytics [ 66 , 68 , 81 ]. Finally, future research should explore how digital technologies enable the transformation of business models in inbound, outbound, and reverse logistics.

Research direction #7

To explore novel Business Models frameworks for advancing Circular Economy, environmental sustainability, and Industry 4.0.

In cluster 1 it is highlighted that numerous studies have examined I4.0 as an enabler of environmental sustainability and discussed the sustainability impacts of the adoption of I4.0 technologies. However, both researchers and industries have been focusing on how the adoption of I4.0 technologies can drive sustainability. On the other hand, there has been relatively little research on how environmental sustainability can strategically drive the adoption of I4.0 technologies, and the digitalization process of companies and supply chains alike, understanding how a strategic path towards increasing circularity and achieving, e.g., “Net zero” could be undertaken by incorporating investment in digital technologies. This represents a crucial area for future research area [ 4 ].

Research direction #8

To investigate environmental sustainability as a driver for Industry 4.0 adoption.

As promising research directions for sustainable additive manufacturing, Cluster 2 emphasized the combined development of eco-friendly and recycled materials with a technological advancement of 3D printing processes. This involves evaluating different recycling and manufacturing methods, as well as assessing the environmental footprint of the materials used [ 65 ]. Some potential areas of investigation involve designing and developing systems to save resources, reduce energy consumption, and optimize labor and material costs. Future research should address how to use secondary raw materials as additive manufacturing powders and design reverse supply chains to collect them and connect various stakeholders [ 63 , 65 ].

Research direction #9

To develop Sustainable Additive Manufacturing materials, technologies, processes, and supply chains.

Future research should advance the understanding of the relationships between dynamic capabilities and the adoption of CE practices, as mentioned in Cluster 6. More specifically, research should address how firms can develop, acquire, and improve dynamic capabilities and resilience using I4.0 technologies in manufacturing supply chains to adapt to changes and environmental uncertainties. Further investigation is needed to overcome the challenge of developing dynamic capabilities in isolation and identify the roles of different stakeholders in supporting CE transition for enhanced resilience [ 83 ].

Research direction #10

To explore the role of Dynamic Capabilities in the adoption of Circular Economy practices for Sustainable, Circular, and Digital (Re)Manufacturing.

Despite the significant research interest in the role of I4.0 technologies for environmental sustainability and CE, the literature on this topic remains sparse and fragmented. This study provided a systematic understanding of all these three dimensions. By analyzing a vast amount of literature, this bibliometric review pointed out the most active countries and influential journals within these areas of study. Additionally, a network-based analysis has led to the identification of eight major clusters that shed light on key research areas and themes. A large amount of literature has adopted a high-level conceptual approach (in particular Cluster 1 addressing the linkage between ‘General Sustainability and Industry 4.0’; Cluster 2 discussing the impacts of ‘General Circular economy and Industry 4.0’) while other studies have a more specific focus on one or few technologies on a more narrow domain (Cluster 3 focusing on the role of Big Data analytics in supply chains; Cluster 4 on ‘additive manufacturing’ in R&D and production process, Cluster 7 on Blockchain). Finally, some clusters have a stronger focus on the application domain (Cluster 5 on ‘urban sustainability’; Cluster 6 on manufacturing and remanufacturing; Cluster 8 discussing several sectorial applications). In conclusion, a structured and comprehensive research agenda is identified. This agenda includes ten promising research directions for scholars in this field. These directions encompass development at the technological level (data integration, security), material level (additive manufacturing), social dimensions, general policy dimensions, and managerial dimensions. The research agenda lays a solid foundation for future investigations in this field.

From a managerial point of view, this bibliometric literature review offers a valuable resource for practitioners and policymakers, enabling them to leverage the insights gained from prior research to raise and support awareness. By exploring our clustering of the research, stakeholders can acquire a comprehensive understanding of the topics and themes investigated and use the findings in their operative environments.

Like other bibliometric literature reviews, our findings are subject to some limitations. The review exclusively focused on peer-reviewed journal papers indexed in Elsevier's Scopus database. To enhance the comprehensiveness of this review, it would be beneficial to include additional data sources and databases, and in particular the grey literature, that can provide valuable knowledge on the practical advancements in these domains. Lastly, and considering the speed with which literature on these topics increase over time, the authors advise future research to repeat such bibliometric analysis in the next years and compare the updated findings with our clusters and research agenda.

Data Availability

Relevant data and materials used to conduct this research are provided in the supplementary materials. Additional data can be provided upon request.

Kristoffersen E, Blomsma F, Mikalef P, Li J (2020) The smart circular economy: a digital-enabled circular strategies framework for manufacturing companies. J Bus Res 120:241–261. https://doi.org/10.1016/j.jbusres.2020.07.044

Article Google Scholar

Corsini F, Gusmerotti NM, Frey M (2023) Fostering the circular economy with blockchain technology: insights from a bibliometric approach. Circ Econ Sustain. https://doi.org/10.1007/s43615-023-00250-9

Fraga-Lamas P, Lopes SI, Fernández-Caramés TM (2021) Green iot and edge AI as key technological enablers for a sustainable digital transition towards a smart circular economy: an industry 5.0 use case. Sensors 21:. https://doi.org/10.3390/s21175745

Beltrami M, Orzes G, Sarkis J, Sartor M (2021) Industry 4.0 and sustainability: Towards conceptualization and theory. J Clean Prod 312:127733. https://doi.org/10.1016/j.jclepro.2021.127733

Ejsmont K, Gladysz B, Kluczek A (2020) Impact of industry 4.0 on sustainability—bibliometric literature review. Sustainability 12:5650. https://doi.org/10.3390/su12145650

Geissdoerfer M, Savaget P, Bocken NMP, Hultink EJ (2017) The circular economy – a new sustainability paradigm? J Clean Prod 143:757–768. https://doi.org/10.1016/j.jclepro.2016.12.048

Nikolaou IE, Jones N, Stefanakis A (2021) Circular economy and sustainability: the past, the present and the future directions. Circ Econ Sustain 1:1–20. https://doi.org/10.1007/s43615-021-00030-3

Hernandez Korner ME, Lambán MP, Albajez JA et al (2020) Systematic literature review: integration of additive manufacturing and industry 4.0. Metals (Basel) 10:1061. https://doi.org/10.3390/met10081061

Nara EOB, da Costa MB, Baierle IC et al (2021) Expected impact of industry 4.0 technologies on sustainable development: a study in the context of Brazil’s plastic industry. Sustain Prod Consum 25:102–122. https://doi.org/10.1016/j.spc.2020.07.018

Montag L (2023) Circular economy and supply chains: definitions, conceptualizations, and research agenda of the circular supply chain framework. Circ Econ Sustain 3:35–75. https://doi.org/10.1007/s43615-022-00172-y

Brundtland GH (1987) Our common future—Call for action. Environ Conserv 14(4):291–294

MacArthur E (2013) Towards the circular economy. J Ind Ecol 2(1):23–44

Bressanelli G, Perona M, Saccani N (2019) Challenges in supply chain redesign for the circular economy: a literature review and a multiple case study. Int J Prod Res 57:7395–7422. https://doi.org/10.1080/00207543.2018.1542176

Kirchherr J, Reike D, Hekkert M (2017) Conceptualizing the circular economy: an analysis of 114 definitions. Resour Conserv Recycl 127:221–232

Bocken NMP, de Pauw I, Bakker C, van der Grinten B (2016) Product design and business model strategies for a circular economy. J Ind Prod Eng 33:308–320. https://doi.org/10.1080/21681015.2016.1172124

Ghobakhloo M, Fathi M, Iranmanesh M et al (2021) Industry 4.0 ten years on: a bibliometric and systematic review of concepts, sustainability value drivers, and success determinants. J Clean Prod 302:127052. https://doi.org/10.1016/j.jclepro.2021.127052

Chauhan C, Parida V, Dhir A (2022) Linking circular economy and digitalisation technologies: a systematic literature review of past achievements and future promises. Technol Forecast Soc Change 177:. https://doi.org/10.1016/j.techfore.2022.121508

Raut RD, Mangla SK, Narwane VS et al (2021) Big data analytics as a mediator in lean, agile, resilient, and green (LARG) practices effects on sustainable supply chains. Transp Res E Logist Transp Rev 145:102170. https://doi.org/10.1016/j.tre.2020.102170

Korner MEH, Lambán MP, Albajez JA et al (2020) Systematic literature review: integration of additive manufacturing and industry 4.0. Metals (Basel) 10:1–24. https://doi.org/10.3390/met10081061

Hettiarachchi BD, Seuring S, Brandenburg M (2022) Industry 4.0-driven operations and supply chains for the circular economy: a bibliometric analysis. Oper Manag Res 15:858–878. https://doi.org/10.1007/s12063-022-00275-7

Salvador R, Barros MV, Freire F et al (2021) Circular economy strategies on business modelling: Identifying the greatest influences. J Clean Prod 299:126918. https://doi.org/10.1016/j.jclepro.2021.126918

Bressanelli G, Adrodegari F, Pigosso DCAA, Parida V (2022) Towards the smart circular economy paradigm: a definition, conceptualization, and research agenda. Sustainability (Switzerland) 14:4960. https://doi.org/10.3390/su14094960

Kiel D, Muller JM, Arnold C, Voigt K-I (2017) Sustainable industrial value creation: benefits and challenges of industry 4.0. Int J Innov Manag 21:1740015. https://doi.org/10.1142/S1363919617400151

Kayikci Y, Kazancoglu Y, Gozacan-Chase N et al (2022) Assessing smart circular supply chain readiness and maturity level of small and medium-sized enterprises. J Bus Res 149:375–392. https://doi.org/10.1016/j.jbusres.2022.05.042

Dantas TET, de Souza ED, Destro IR et al (2021) How the combination of Circular Economy and Industry 4.0 can contribute towards achieving the sustainable development goals. Sustain Prod Consum 26:213–227. https://doi.org/10.1016/j.spc.2020.10.005

Laskurain-Iturbe I, Arana-Landín G, Landeta-Manzano B, Uriarte-Gallastegi N (2021) Exploring the influence of industry 4.0 technologies on the circular economy. J Clean Prod 321:128944. https://doi.org/10.1016/j.jclepro.2021.128944

Ghobakhloo M (2020) Industry 4.0, digitization, and opportunities for sustainability. J Clean Prod 252:119869. https://doi.org/10.1016/j.jclepro.2019.119869

de Oliveira Neto GC, da Conceição SA, Filho MG (2023) How can Industry 4.0 technologies and circular economy help companies and researchers collaborate and accelerate the transition to strong sustainability? A bibliometric review and a systematic literature review. Int J Environ Sci Technol 20:3483–3520. https://doi.org/10.1007/s13762-022-04234-4

Khan IS, Ahmad MO, Majava J (2021) Industry 4.0 and sustainable development: a systematic mapping of triple bottom line, circular economy and sustainable business models perspectives. J Clean Prod 297:126655. https://doi.org/10.1016/j.jclepro.2021.126655

Tavares-Lehmann AT, Varum C (2021) Industry 4.0 and sustainability: a bibliometric literature review. Sustainability (Switzerland) 13:1–15. https://doi.org/10.3390/su13063493

Wu SR, Shirkey G, Celik I et al (2022) A review on the adoption of AI, BC, and IoT in sustainability research. Sustainability (Switzerland) 14:7851. https://doi.org/10.3390/su14137851

Abideen AZ, Pyeman J, Sundram VPK et al (2021) Leveraging capabilities of technology into a circular supply chain to build circular business models: a state-of-the-art systematic review. Sustainability (Switzerland) 13:8997. https://doi.org/10.3390/su13168997

Hettiarachchi BD, Brandenburg M, Seuring S et al (2022) Connecting additive manufacturing to circular economy implementation strategies: Links, contingencies and causal loops. Int J Prod Econ 246:108414. https://doi.org/10.1016/j.ijpe.2022.108414

Shashi CP, Cerchione R et al (2023) What we learn is what we earn from sustainable and circular construction. J Clean Prod 382:135183. https://doi.org/10.1016/j.jclepro.2022.135183

Yi H, Yang J (2014) Research trends of post disaster reconstruction: the past and the future. Habitat Int 42:21–29. https://doi.org/10.1016/j.habitatint.2013.10.005

Donthu N, Kumar S, Mukherjee D et al (2021) How to conduct a bibliometric analysis: an overview and guidelines. J Bus Res 133:285–296. https://doi.org/10.1016/j.jbusres.2021.04.070

Goyal S, Chauhan S, Mishra P (2021) Circular economy research: a bibliometric analysis (2000–2019) and future research insights. J Clean Prod 287:125011. https://doi.org/10.1016/j.jclepro.2020.125011

Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:. https://doi.org/10.1371/journal.pmed.1000097

van Eck NJ, Waltman L, Jan N, Ludo VE (2010) Software survey: VOSviewer, a computer program for bibliometric mapping. Scientometrics 84:523–538. https://doi.org/10.1007/s11192-009-0146-3

Massaro M, Secinaro S, Dal Mas F et al (2021) Industry 4.0 and circular economy: an exploratory analysis of academic and practitioners’ perspectives. Bus Strategy Environ 30:1213–1231. https://doi.org/10.1002/bse.2680

van Eck NJ, Waltman L (2013) VOSviewer manual. Univeristeit Leiden, Leiden

Google Scholar

Zhang X, Yu Y, Zhang N (2021) Sustainable supply chain management under big data : a bibliometric analysis. 34:427–445. https://doi.org/10.1108/JEIM-12-2019-0381

Bressanelli G, Pigosso DCA, Saccani N, Perona M (2021) Enablers, levers and benefits of circular economy in the electrical and electronic equipment supply chain: a literature review. J Clean Prod 298:126819. https://doi.org/10.1016/j.jclepro.2021.126819

Maditati DR, Munim ZH, Schramm H-J, Kummer S (2018) A review of green supply chain management: from bibliometric analysis to a conceptual framework and future research directions. Resour Conserv Recycl 139:150–162. https://doi.org/10.1016/j.resconrec.2018.08.004

El Baz J, Tiwari S, Akenroye T et al (2022) A framework of sustainability drivers and externalities for Industry 4.0 technologies using the Best-Worst Method. J Clean Prod 344:130909. https://doi.org/10.1016/j.jclepro.2022.130909

Felsberger A, Reiner G (2020) Sustainable industry 4.0 in production and operations management: a systematic literature review. Sustainability (Switzerland) 12:1–39. https://doi.org/10.3390/su12197982

Birkel H, Müller JM (2021) Potentials of industry 4.0 for supply chain management within the triple bottom line of sustainability – a systematic literature review. J Clean Prod 289:125612. https://doi.org/10.1016/j.jclepro.2020.125612

Samadhiya A, Agrawal R, Luthra S et al (2023) Total productive maintenance and industry 4.0 in a sustainability context: exploring the mediating effect of circular economy. Int J Logist Manag 34:818–846. https://doi.org/10.1108/IJLM-04-2022-0192

Gebhardt M, Kopyto M, Birkel H, Hartmann E (2022) Industry 4.0 technologies as enablers of collaboration in circular supply chains: a systematic literature review. Int J Prod Res 60:6967–6995. https://doi.org/10.1080/00207543.2021.1999521

Liu Q, Liu Z, Xu W et al (2019) Human-robot collaboration in disassembly for sustainable manufacturing. Int J Prod Res 57:4027–4044. https://doi.org/10.1080/00207543.2019.1578906

Potting J, Hekkert MP, Worrell E, Hanemaaijer A (2017) Circular economy: measuring innovation in the product chain. Planbureau voor de Leefomgeving, (2544)

Khan SAR, Shah ASA, Yu Z, Tanveer M (2022) A systematic literature review on circular economy practices: challenges, opportunities and future trends. J Entrep Emerg Econ 14:754–795. https://doi.org/10.1108/JEEE-09-2021-0349

Kamble SS, Gunasekaran A (2023) Analysing the role of Industry 4.0 technologies and circular economy practices in improving sustainable performance in Indian manufacturing organisations. Prod Plan Control 34:887–901. https://doi.org/10.1080/09537287.2021.1980904

Rejeb A, Suhaiza Z, Rejeb K et al (2022) The internet of things and the circular economy: a systematic literature review and research agenda. J Clean Prod 350:131439. https://doi.org/10.1016/j.jclepro.2022.131439

Di Maria E, De Marchi V, Galeazzo A (2022) Industry 4.0 technologies and circular economy: the mediating role of supply chain integration. Bus Strat Environ 31:619–632. https://doi.org/10.1002/bse.2940

Akbari M, Hopkins JL (2022) Digital technologies as enablers of supply chain sustainability in an emerging economy. Oper Manag Res 15:689–710. https://doi.org/10.1007/s12063-021-00226-8

Stroumpoulis A, Kopanaki E (2022) Theoretical perspectives on sustainable supply chain management and digital transformation: a literature review and a conceptual framework. Sustainability 14:4862. https://doi.org/10.3390/su14084862

Aldrighetti R, Battini D, Das A et al (2023) The performance impact of Industry 4.0 technologies on closed-loop supply chains: insights from an Italy based survey. https://doi.org/10.1080/00207543.2022.2075291

Bag S, Wood LC, Telukdarie A et al (2023) The management of operations application of industry 4.0 tools to empower circular economy and achieving sustainability in supply chain operations. Prod Plan Control 34:918–940. https://doi.org/10.1080/09537287.2021.1980902

Kumar P, Singh RK, Kumar V et al (2021) Managing supply chains for sustainable operations in the era of industry 4.0 and circular economy: analysis of barriers. Resour Conserv Recycl 164:105215. https://doi.org/10.1016/j.resconrec.2020.105215

Dahmani N, Benhida K, Belhadi A et al (2021) Smart circular product design strategies towards eco-effective production systems: a lean eco-design industry 4.0 framework. J Clean Prod 320:128847. https://doi.org/10.1016/j.jclepro.2021.128847

Cruz Sanchez FA, Boudaoud H, Camargo M, Pearce JM (2020) Plastic recycling in additive manufacturing: a systematic literature review and opportunities for the circular economy. J Clean Prod 264:121602. https://doi.org/10.1016/j.jclepro.2020.121602

Godina R, Matos F, Ferreira BT et al (2020) Impact assessment of additive manufacturing on sustainable business models in industry 4.0 context. Sustainability (Switzerland) 12:1–21. https://doi.org/10.3390/su12177066

Mele M, Campana G (2022) Advancing towards sustainability in liquid crystal display 3D printing via adaptive slicing. Sustain Prod Consum 30:488–505. https://doi.org/10.1016/j.spc.2021.12.024

Kellens K, Baumers M, Gutowski TG et al (2017) Environmental dimensions of additive manufacturing: mapping application domains and their environmental implications. J Ind Ecol 21:49–68. https://doi.org/10.1111/jiec.12629

Bibri SE, Krogstie J (2020) Environmentally data-driven smart sustainable cities: applied innovative solutions for energy efficiency, pollution reduction, and urban metabolism. Energy Informatics 3:. https://doi.org/10.1186/s42162-020-00130-8

Bibri SE (2019) On the sustainability of smart and smarter cities in the era of big data: an interdisciplinary and transdisciplinary literature review. J Big Data 6:25. https://doi.org/10.1186/s40537-019-0182-7

Kurniawan TA, Dzarfan Othman MH, Hwang GH, Gikas P (2022) Unlocking digital technologies for waste recycling in Industry 4.0 era: a transformation towards a digitalization-based circular economy in Indonesia. J Clean Prod 357:131911. https://doi.org/10.1016/j.jclepro.2022.131911

Article CAS Google Scholar

Chau MQ, Nguyen XP, Huynh TT et al (2021) Prospects of application of IoT-based advanced technologies in remanufacturing process towards sustainable development and energy-efficient use. Energy Sources, Part A: Recover, Utilization, Environ Effects 1–25. https://doi.org/10.1080/15567036.2021.1994057

Kerin M, Pham DT (2019) A review of emerging industry 4.0 technologies in remanufacturing. J Clean Prod 237:117805. https://doi.org/10.1016/j.jclepro.2019.117805

Chauhan C, Sharma A, Singh A (2021) A SAP-LAP linkages framework for integrating Industry 4.0 and circular economy. Benchmark: Int J 28:1638–1664. https://doi.org/10.1108/BIJ-10-2018-0310

de Sousa L, Jabbour AB, Jabbour CJC, Godinho Filho M, Roubaud D (2018) Industry 4.0 and the circular economy: a proposed research agenda and original roadmap for sustainable operations. Ann Oper Res 270:273–286. https://doi.org/10.1007/s10479-018-2772-8

Rajput S, Singh SP (2019) Connecting circular economy and industry 4.0. Int J Inf Manage 49:98–113. https://doi.org/10.1016/j.ijinfomgt.2019.03.002

Zhang A, Zhong RY, Farooque M et al (2020) Blockchain-based life cycle assessment: an implementation framework and system architecture. Resour Conserv Recycl 152:104512. https://doi.org/10.1016/j.resconrec.2019.104512

Varriale V, Cammarano A, Michelino F, Caputo M (2021) Sustainable supply chains with blockchain, IoT and RFID: a simulation on order management. Sustainability (Switzerland) 13:6372. https://doi.org/10.3390/su13116372

Umar M, Khan SAR, Yusoff Yusliza M et al (2022) Industry 4.0 and green supply chain practices: an empirical study. Int J Product Perform Manag 71:814–832. https://doi.org/10.1108/IJPPM-12-2020-0633

Piyathanavong V, Huynh V-N, Karnjana J, Olapiriyakul S (2022) Role of project management on sustainable supply chain development through Industry 4.0 technologies and circular economy during the COVID-19 pandemic: a multiple case study of Thai metals industry. Oper Manag Res. https://doi.org/10.1007/s12063-022-00283-7

Vimal KEK, Churi K, Kandasamy J (2022) Analysing the drivers for adoption of Industry 4.0 technologies in a functional paper – cement – sugar circular sharing network. Sustain Prod Consum 31:459–477. https://doi.org/10.1016/j.spc.2022.03.006

Atif S, Ahmed S, Wasim M et al (2021) Towards a conceptual development of industry 4.0, servitisation, and circular economy: a systematic literature review. Sustainability (Switzerland) 13:. https://doi.org/10.3390/su13116501

Jeble S, Dubey R, Childe SJ et al (2018) Impact of big data and predictive analytics capability on supply chain sustainability. Int J Logist Manag 29:513–538. https://doi.org/10.1108/IJLM-05-2017-0134

Bibri SE (2019) On the sustainability of smart and smarter cities in the era of big data : an interdisciplinary and transdisciplinary literature review. J Big Data. https://doi.org/10.1186/s40537-019-0182-7

Belhadi A, Kamble SS, Jose C et al (2022) International journal of production economics a self-assessment tool for evaluating the integration of circular economy and industry 4.0 principles in closed-loop supply chains. Int J Prod Econ 245:108372. https://doi.org/10.1016/j.ijpe.2021.108372

Chari A, Niedenzu D, Despeisse M et al (2022) Dynamic capabilities for circular manufacturing supply chains—exploring the role of Industry 4.0 and resilience. Bus Strategy Environ 31:2500–2517. https://doi.org/10.1002/bse.3040

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Das, S.K., Bressanelli, G. & Saccani, N. Clustering the Research at the Intersection of Industry 4.0 Technologies, Environmental Sustainability and Circular Economy: Evidence from Literature and Future Research Directions. Circ.Econ.Sust. (2024). https://doi.org/10.1007/s43615-024-00393-3

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Digital twin—a review of the evolution from concept to technology and its analytical perspectives on applications in various fields.

1. Introduction

2. literature review methodology, 3. digital twin, from concept to architecture model, 3.1. the concept of digital twins.

High degree of accuracy: From the appearance, functionalities, and content point of view, the DT must be an accurate copy of its physical counterpart. Thus, the higher the precision, the actions and simulation scenarios should achieve the same behavior both in the physical and virtual environment.
Dynamic: Communication between the physical product and its virtual twin must be continuous and bidirectional, and any change made to one must be reflected in the behavior of the other.
Self-evolving: Throughout the life cycle, the DT follows the changes along with its physical counterpart. The DT adapts and optimizes with the aid of the data received from the physical counterpart in real time, evolving with it.
Identifiable: Each real product must have its own DT. During the product life cycle, information and functional models evolve, and based on this, at any point in time, the DT can be identified in a unique mode from its physical twin [ 11 ].

3.2. Classification of Digital Twins

Digital Twin Prototype (DTP): The DTP is the DT that contains the essential information for creating a physical copy of a virtual version. The product cycle will be initiated upon achievement of the DTP, which undergoes several tests before the physical twin is created. Once the DTP is realized and validated, its physical counterpart can be produced in the real environment. The simulation accuracy determines the physical twin quality.
Digital Twin Instance (DTI): The DTI originates in the production phase and is a DT that is strongly correlated, throughout its life cycle. After building the physical system, real space data are transmitted to digital space and, reversely, to predict and monitor the system behavior.
Predictive DT: DT predicts the behavior and performance of its physical counterpart.
Interrogative DT: The DT is used to query the status of its counterpart.
Digital Model: The data between the physical and virtual object are manually changed by the user. Any change to the state of the physical object is not reflected in the virtual object, and any change to the state of the virtual object is not reflected in the physical object.
Digital Shadow: The data of the physical object is automatically transmitted to the virtual object, so there is one-way communication between the two objects.
Digital Twin: This DT category involves a two-way data transmission between the physical twin and the digital one, and any modification made to both the physical and the digital object will be reflected in the behavior of its counterpart.
Predictive Digital Twin: Like the normal Digital Twin, it is characterized by continuous, real-time communication between the two components. The novelty brought by the Predictive DT consists of the fact that the digital twin also contains cyber security components and artificial intelligence algorithms that increase the accuracy of the simulation results and allow predictions to be made.
Product DT: DT is used for prototyping, and various conditions are analyzed, which helps to confirm that the physical product behaves according to the desired standards.
Production DT: DT is used before actual production and has a role in process validation, simulation and analysis. It also helps develop efficient production methodologies.
Performance DT: This DT can include both actual product and production performance and is used for decision-making processes by receiving, integrating, and analyzing product data. It also optimizes operations based on resource availability, providing the opportunity to improve product and production DT through a feedback loop.
Unit level: Represents the smallest unit participating in production and examines the functional, geometric, behavioral, and operational model of the physical counterpart unit level.
System level: Represents a collaboration of unit-level DTs, and each unit-level DT represents a component of the new system.
System of Systems (SoSs) level: Represents the connection of multiple system-level DTs to form a system of systems. The system-of-systems DT also includes various phases throughout the life cycle of a product.
Partial DT: May contain parameters (pressure, temperature, humidity) and is used to determine the DT functionality and connectivity.
DT Clone: It is used to make prototypes that are made by means of the relevant data about the product/system. The data are contained in this DT.
Augmented DT: It has the role of making a correlation between current data and past data based on algorithms and analyses.
Pre-Digital Twin: In this stage, the DT is created before the physical object and is used in the process of decision making, referring to the prototype to reduce the risks that may arise.
Digital Twin: It represents the second stage, and at its level, the data of the physical product are incorporated. It is applied in the design and development decision-making phases of the product life cycle, and data transfer to it is realized in both senses.
Adaptive Digital Twin: The DT offers a dynamic interface between the DT itself and the physical object. It has the ability of priority learning and can maintain the human operators preferences with the help of supervised machine learning process. Operation’s real-time decision-making and planning are also noted as advantages.
Intelligent Digital Twin: Unlike the Adaptive DT, this DT offers unsupervised machine learning functionality, increasing its autonomy. It also provides higher accuracy and efficient system analysis.

3.3. Digital Twin Models, Frameworks, and Architectures

The integration of different perspectives to achieve a complex framework regarding the use of the Digital Twin in Industry 4.0.
Addressing requirements according to production paradigms that make the transition from mass production to customized production.
Decomposition of a process into sub-processes, which can be approached and adapted with respect to the vertical axis.
Integration of relationships between different levels, which is achieved through the iterative and incremental process.

4. Analyses of the Applications of Digital Twin Models

4.1. manufacturing, 4.1.1. application and adoption of digital twin in manufacturing.

Remote control and monitoring in real-time: the digital twin can be monitored and controlled at any time from any location.
Increased safety and efficiency: integrating quantitative data and performing complex analyses in real time.
Predictive maintenance and planning, achieved by continuously analyzing data and taking measures so that the impact of failures is minimal or eliminated.
Assessment of risks through simulations to take place at the level of the digital twin and finding methods to mitigate risks highlighted from a primary phase of the life cycle.
Rapid and continuous customization of products and services according to current trends and customer requirements.

4.1.2. Benefits and Challenges of Digital Twins in Manufacturing

4.2. medicine, 4.2.1. application and adoption of digital twin in medicine, 4.2.2. benefits and challenges of digital twins in medicine, 4.3. digital twin in other domains, benefits and challenges of digital twins in other domains, 6. discussion, 7. conclusions, author contributions, institutional review board statement, informed consent statement, data availability statement, conflicts of interest.

Qi, Q.; Tao, F.; Hu, T.; Anwer, N.; Liu, A.; Wei, Y.; Wang, L.; Nee, A.Y.C. Enabling technologies and tools for digital twin. J. Manuf. Syst. 2021 , 58 , 3–21. [ Google Scholar ] [ CrossRef ]
Grieves, M. Digital twin: Manufacturing excellence through virtual factory replication. White Pap. 2014 , 1 , 1–7. [ Google Scholar ]
Glaessgen, E.; Stargel, D. The digital twin paradigm for future NASA and US Air Force vehicles. In Proceedings of the 53rd AIAA/ASME/ASCE/AHS/ASC Structures, Structural Dynamics and Materials Conference 20th AIAA/ASME/AHS Adaptive Structures Conference 14th AIAA, Honolulu, HI, USA, 23–26 April 2012; p. 1818. [ Google Scholar ]
Tao, F.; Zhang, M.; Cheng, J.; Qi, Q. Digital twin workshop: A new paradigm for future workshop. Comput. Integr. Manuf. Syst. 2017 , 23 , 1–9. [ Google Scholar ]
Tao, F.; Liu, W.; Zhang, M.; Hu, T.; Qi, Q.; Zhang, H.; Sui, F.; Wang, T.; Xu, H.; Huang, Z.; et al. Five-dimension digital twin model and its ten applications. Comput. Integr. Manuf. Syst. 2019 , 25 , 1–18. [ Google Scholar ]
Negri, E.; Fumagalli, L.; Macchi, M. A review of the roles of digital twin in CPS-based production systems. Procedia Manuf. 2017 , 11 , 939–948. [ Google Scholar ] [ CrossRef ]
Autiosalo, J. Platform for industrial internet and digital twin focused education, research, and innovation: Ilmatar the overhead crane. In Proceedings of the 2018 IEEE 4th World Forum on Internet of Things (WF-IoT), Singapore, 5–8 February 2018; pp. 241–244. [ Google Scholar ]
Boschert, S.; Rosen, R. Digital twin: The simulation aspect. In Mechatronic Futures ; Springer: Cham, Switzerland, 2016; pp. 59–74. [ Google Scholar ]
Tao, F.; Zhang, H.; Liu, A.; Nee, A.Y. Digital twin in industry: State-of-the-art. IEEE Trans. Ind. Inform. 2018 , 15 , 2405–2415. [ Google Scholar ] [ CrossRef ]
Zheng, Y.; Yang, S.; Cheng, H. An application framework of digital twin and its case study. J. Ambient. Intell. Humaniz. Comput. 2019 , 10 , 1141–1153. [ Google Scholar ] [ CrossRef ]
Singh, M.; Fuenmayor, E.; Hinchy, E.P.; Qiao, Y.; Murray, N.; Devine, D. Digital twin: Origin to future. Appl. Syst. Innov. 2021 , 4 , 36. [ Google Scholar ] [ CrossRef ]
Grieves, M.; Vickers, J. Digital twin: Mitigating unpredictable, undesirable emergent behavior in complex systems. In Transdisciplinary Perspectives on Complex Systems ; Springer: Cham, Switzerland, 2017; pp. 85–113. [ Google Scholar ]
Kritzinger, W.; Karner, M.; Traar, G.; Henjes, J.; Sihn, W. Digital Twin in manufacturing: A categorical literature review and classification. IFAC-Pap. 2018 , 51 , 1016–1022. [ Google Scholar ] [ CrossRef ]
Digital Twin. Available online: https://www.plm.automation.siemens.com/global/en/our-story/glossary/digital-twin/24465 (accessed on 12 October 2020).
Exosite. The 3 Types of Digital Twin Maturity Models. 2017. Available online: https://blog.exosite.com/3-digital-twin-maturity-models (accessed on 1 May 2022).
Madni, A.M.; Madni, C.C.; Lucero, S.D. Leveraging digital twin technology in model-based systems engineering. Systems 2019 , 7 , 7. [ Google Scholar ] [ CrossRef ]
Malakuti, S.; Grüner, S. Architectural aspects of digital twins in IIoT systems. In Proceedings of the 12th European Conference on Software Architecture: Companion Proceedings ECSA Companion, Madrid, Spain, 24–28 September 2018. [ Google Scholar ]
Lu, Y.; Liu, C.; Kevin, I.; Wang, K.; Huang, H.; Xu, X. Digital Twin-driven smart manufacturing: Connotation, reference model, applications and research issues. Robot. Comput. Integr. Manuf. 2020 , 61 , 101837. [ Google Scholar ] [ CrossRef ]
Alam, K.M.; El Saddik, A. C2PS: A digital twin architecture reference model for the cloud-based cyber-physical systems. IEEE Access 2017 , 5 , 2050–2062. [ Google Scholar ] [ CrossRef ]
Bevilacqua, M.; Bottani, E.; Ciarapica, F.E.; Costantino, F.; Di Donato, L.; Ferraro, A.; Mazzuto, G.; Monteriù, A.; Nardini, G.; Ortenzi, M.; et al. Digital twin reference model development to prevent operators’ risk in process plants. Sustainability 2020 , 12 , 1088. [ Google Scholar ] [ CrossRef ]
Pisching, M.A.; Pessoa, M.A.; Junqueira, F.; dos Santos Filho, D.J.; Miyagi, P.E. An architecture based on RAMI 4.0 to discover equipment to process operations required by products. Comput. Ind. Eng. 2018 , 125 , 574–591. [ Google Scholar ] [ CrossRef ]
ISO 23247-2:2021 ; Automation Systems and Integration — Digital Twin Framework for Manufacturing — Part 2: Reference Architecture, Edition 1. ISO: Geneva, Switzerland, 2021.
Aheleroff, S.; Xu, X.; Zhong, R.Y.; Lu, Y. Digital twin as a service (DTaaS) in industry 4.0: An architecture reference model. Adv. Eng. Inform. 2021 , 47 , 101225. [ Google Scholar ] [ CrossRef ]
Kontar, R.; Shi, N.; Yue, X.; Chung, S.; Byon, E.; Chowdhury, M.; Jin, J.; Kontar, W.; Masoud, N.; Nouiehed, M.; et al. The internet of federated things (IoFT). IEEE Access 2021 , 9 , 156071–156113. [ Google Scholar ] [ CrossRef ]
Smith, V.; Chiang, C.K.; Sanjabi, M.; Talwalkar, A.S. Federated multi-task learning. In Advances in Neural Information Processing Systems ; Neural Information Processing Systems Foundation, Inc. (NeurIPS): La Jolla, CA, USA, 2017; Volume 30. [ Google Scholar ]
Snell, J.; Swersky, K.; Zemel, R. Prototypical networks for few-shot learning. In Advances in Neural Information Processing Systems ; Neural Information Processing Systems Foundation, Inc. (NeurIPS): La Jolla, CA, USA, 2017; Volume 30. [ Google Scholar ]
Liu, M.; Fang, S.; Dong, H.; Xu, C. Review of digital twin about concepts, technologies, and industrial applications. J. Manuf. Syst. 2021 , 58 , 346–361. [ Google Scholar ] [ CrossRef ]
Rosen, R.; Von Wichert, G.; Lo, G.; Bettenhausen, K.D. About the importance of autonomy and digital twins for the future of manufacturing. IFAC-Pap. 2015 , 48 , 567–572. [ Google Scholar ] [ CrossRef ]
Park, K.T.; Nam, Y.W.; Lee, H.S.; Im, S.J.; Noh, S.D.; Son, J.Y.; Kim, H. Design and implementation of a digital twin application for a connected micro smart factory. Int. J. Comput. Integr. Manuf. 2019 , 32 , 596–614. [ Google Scholar ] [ CrossRef ]
Tao, F.; Zhang, M. Digital twin shop-floor: A new shop-floor paradigm towards smart manufacturing. IEEE Access 2017 , 5 , 20418–20427. [ Google Scholar ] [ CrossRef ]
Bertoni, M.; Bertoni, A. Designing solutions with the product-service systems digital twin: What is now and what is next? Comput. Ind. 2022 , 138 , 103629. [ Google Scholar ] [ CrossRef ]
Wang, X.; Wang, Y.; Tao, F.; Liu, A. New paradigm of data-driven smart customization through digital twin. J. Manuf. Syst. 2021 , 58 , 270–280. [ Google Scholar ] [ CrossRef ]
Meierhofer, J.; West, S.; Rapaccini, M.; Barbieri, C. The digital twin as a service enabler: From the service ecosystem to the simulation model. In Exploring Services Science, Proceedings of the 10th International Conference, IESS 2020, Porto, Portugal, 5–7 February 2020 ; Springer: Cham, Switzerland, 2020; pp. 347–359. [ Google Scholar ]
Li, X.; Wang, Z.; Chen, C.H.; Zheng, P. A data-driven reversible framework for achieving Sustainable Smart product-service systems. J. Clean. Prod. 2021 , 279 , 123618. [ Google Scholar ] [ CrossRef ]
Kaewunruen, S.; Peng, S.; Phil-Ebosie, O. Digital twin aided sustainability and vulnerability audit for subway stations. Sustainability 2020 , 12 , 7873. [ Google Scholar ] [ CrossRef ]
Zhang, H.; Ma, L.; Sun, J.; Lin, H.; Thürer, M. Digital twin in services and industrial product service systems: Review and analysis. Procedia CIRP 2019 , 83 , 57–60. [ Google Scholar ] [ CrossRef ]
Bagozi, A.; Bianchini, D.; De Antonellis, V.; Marini, A.; Ragazzi, D. Interactive data exploration as a service for the smart factory. In Proceedings of the 2017 IEEE International Conference on Web Services (ICWS), Honolulu, HI, USA, 25–30 June 2017; pp. 293–300. [ Google Scholar ]
Olivotti, D.; Dreyer, S.; Lebek, B.; Breitner, M.H. Creating the foundation for digital twins in the manufacturing industry: An integrated installed base management system. Inf. Syst. Bus. Manag. 2019 , 17 , 89–116. [ Google Scholar ] [ CrossRef ]
Bonnard, R.; Hascoët, J.Y.; Mognol, P. Data model for additive manufacturing digital thread: State of the art and perspectives. Int. J. Comput. Integr. Manuf. 2019 , 32 , 1170–1191. [ Google Scholar ] [ CrossRef ]
Minerva, R.; Crespi, N. Digital twins: Properties, software frameworks, and application scenarios. IT Prof. 2021 , 23 , 51–55. [ Google Scholar ] [ CrossRef ]
Wuest, T.; Hribernik, K.; Thoben, K.D. Accessing servitisation potential of PLM data by applying the product avatar concept. Prod. Plan. Control. 2015 , 26 , 1198–1218. [ Google Scholar ] [ CrossRef ]
Ströer, F.; Sivasothy, P.; Faißt, K.G.; Apostolov, H.; Eickhoff, T.; Bechev, D.; Bulun, G.; Seewig, J.; Eigner, M.; Sauer, B. Combined development and test of product-service systems in early product development stages for customized, availability-oriented business models in the capital goods industry. Procedia CIRP 2018 , 72 , 714–719. [ Google Scholar ] [ CrossRef ]
D’Amico, D.; Ekoyuncu, J.; Addepalli, S.; Smith, C.; Keedwell, E.; Sibson, J.; Penver, S. Conceptual framework of a digital twin to evaluate the degradation status of complex engineering systems. Procedia CIRP 2019 , 86 , 61–67. [ Google Scholar ] [ CrossRef ]
Grijalvo Martín, M.; Pacios Álvarez, A.; Ordieres-Meré, J.; Villalba-Díez, J.; Morales-Alonso, G. New business models from prescriptive maintenance strategies aligned with sustainable development goals. Sustainability 2020 , 13 , 216. [ Google Scholar ] [ CrossRef ]
Tao, F.; Sui, F.; Liu, A.; Qi, Q.; Zhang, M.; Song, B.; Guo, Z.; Lu, S.C.-Y.; Nee, A.Y. Digital twin-driven product design framework. Int. J. Prod. Res. 2019 , 57 , 3935–3953. [ Google Scholar ] [ CrossRef ]
Schleich, B.; Anwer, N.; Mathieu, L.; Wartzack, S. Shaping the digital twin for design and production engineering. CIRP Ann. 2017 , 66 , 141–144. [ Google Scholar ] [ CrossRef ]
Macchi, M.; Roda, I.; Negri, E.; Fumagalli, L. Exploring the role of digital twin for asset lifecycle management. IFAC-Pap. 2018 , 51 , 790–795. [ Google Scholar ] [ CrossRef ]
Fang, X.; Wang, H.; Liu, G.; Tian, X.; Ding, G.; Zhang, H. Industry application of digital twin: From concept to implementation. Int. J. Adv. Manuf. Technol. 2022 , 121 , 4289–4312. [ Google Scholar ] [ CrossRef ]
Jia, W.; Wang, W.; Zhang, Z. From simple digital twin to complex digital twin Part I: A novel modeling method for multi-scale and multi-scenario digital twin. Adv. Eng. Inform. 2022 , 53 , 101706. [ Google Scholar ] [ CrossRef ]
Dumitrache, I. Cyber-Physical Systems (CPS) Factor determinant în economia bazată pe inovare şi cunoştinţe. Rev. Română Infor. Autom. 2013 , 23 , 43–54. [ Google Scholar ]
Choi, S.H.; Park, K.B.; Roh, D.H.; Lee, J.Y.; Mohammed, M.; Ghasemi, Y.; Jeong, H. An integrated mixed reality system for safety-aware human-robot collaboration using deep learning and digital twin generation. Robot. Comput. Integr. Manuf. 2022 , 73 , 102258. [ Google Scholar ] [ CrossRef ]
Kousi, N.; Gkournelos, C.; Aivaliotis, S.; Lotsaris, K.; Bavelos, A.C.; Baris, P.; Michalos, G.; Makris, S. Digital twin for designing and reconfiguring human–robot collaborative assembly lines. Appl. Sci. 2021 , 11 , 4620. [ Google Scholar ] [ CrossRef ]
Bilberg, A.; Malik, A.A. Digital twin driven human–robot collaborative assembly. CIRP Ann. 2019 , 68 , 499–502. [ Google Scholar ] [ CrossRef ]
Oracle. About the IoT Digital Twin Framework. Available online: https://docs.oracle.com/en/cloud/paas/iot-cloud/iotgs/iot-digital-twin-framework.html (accessed on 17 June 2024).
Qi, Q.; Tao, F. Digital twin and big data towards smart manufacturing and industry 4.0: 360 degree comparison. IEEE Access 2018 , 6 , 3585–3593. [ Google Scholar ] [ CrossRef ]
He, B.; Bai, K.J. Digital twin-based sustainable intelligent manufacturing: A review. Adv. Manuf. 2021 , 9 , 1–21. [ Google Scholar ] [ CrossRef ]
Wang, Y.; Cao, Y.; Wang, F.Y. Anomaly detection in digital twin model. In Proceedings of the 2021 IEEE 1st International Conference on Digital Twins and Parallel Intelligence (DTPI), Beijing, China, 15 July–15 August 2021; pp. 208–211. [ Google Scholar ]
Augustine, P. The industry use cases for the digital twin idea. In Advances in Computers ; Elsevier: Amsterdan, The Netherlands, 2020; Volume 117, pp. 79–105. [ Google Scholar ]
Xu, Q.; Ali, S.; Yue, T. Digital twin-based anomaly detection in cyber-physical systems. In Proceedings of the 2021 14th IEEE Conference on Software Testing, Verification and Validation (ICST), Porto de Galinhas, Brazil, 12–16 April 2021; pp. 205–216. [ Google Scholar ]
Stary, C.; Elstermann, M.; Fleischmann, A.; Schmidt, W. Behavior-centered digital-twin design for dynamic cyber-physical system development. Complex Syst. Inform. Model. Q. 2022 , 30 , 31–52. [ Google Scholar ] [ CrossRef ]
Steinmetz, C.; Rettberg, A.; Ribeiro, F.G.C.; Schroeder, G.; Pereira, C.E. Internet of things ontology for digital twin in cyber physical systems. In Proceedings of the 2018 VIII Brazilian symposium on computing systems engineering (SBESC), Salvador, Brazil, 5–8 November 2018; pp. 154–159. [ Google Scholar ]
Son, Y.H.; Park, K.T.; Lee, D.; Jeon, S.W.; Do Noh, S. Digital twin–based cyber-physical system for automotive body production lines. Int. J. Adv. Manuf. Technol. 2021 , 115 , 291–310. [ Google Scholar ] [ CrossRef ]
Rasheed, A.; San, O.; Kvamsdal, T. Digital twin: Values, challenges and enablers from a modeling perspective. IEEE Access 2020 , 8 , 21980–22012. [ Google Scholar ] [ CrossRef ]
Bruynseels, K.; Santoni de Sio, F.; Van den Hoven, J. Digital twins in health care: Ethical implications of an emerging engineering paradigm. Front. Genet. 2018 , 9 , 320848. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Zhang, B.; Korolj, A.; Lai, B.F.L.; Radisic, M. Advances in organ-on-a-chip engineering. Nat. Rev. Mater. 2018 , 3 , 257–278. [ Google Scholar ] [ CrossRef ]
Skardal, A.; Shupe, T.; Atala, A. Organoid-on-a-chip and body-on-a-chip systems for drug screening and disease modeling. Drug Discov. Today 2016 , 21 , 1399–1411. [ Google Scholar ] [ CrossRef ]
Jimenez, J.I.; Jahankhani, H.; Kendzierskyj, S. Health care in the cyberspace: Medical cyber-physical system and digital twin challenges. In Digital Twin Technologies and Smart Cities ; Springer: Cham, Switzerland, 2020; pp. 79–92. [ Google Scholar ]
Lee, I.; Sokolsky, O.; Chen, S.; Hatcliff, J.; Jee, E.; Kim, B.; King, A.; Mullen-Fortino, M.; Park, S.; Roederer, A.; et al. Challenges and research directions in medical cyber–physical systems. Proc. IEEE 2011 , 100 , 75–90. [ Google Scholar ]
Dey, N.; Ashour, A.S.; Shi, F.; Fong, S.J.; Tavares, J.M.R. Medical cyber-physical systems: A survey. J. Med. Syst. 2018 , 42 , 74. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Subramanian, B.; Kim, J.; Maray, M.; Paul, A. Digital Twin Model: A Real-Time Emotion Recognition System for Personalized Healthcare. IEEE Access 2022 , 10 , 81155–81165. [ Google Scholar ] [ CrossRef ]
Elayan, H.; Aloqaily, M.; Guizani, M. Digital twin for intelligent context-aware IoT healthcare systems. IEEE Internet Things J. 2021 , 8 , 16749–16757. [ Google Scholar ] [ CrossRef ]
Diaz, V.; Viceconti, M.; Stroetmann, K.; Kalra, D. Roadmap for the Digital Patient ; European Commission: Brussels, Belgium, 2013. [ Google Scholar ]
van Houten, H. How a Virtual Heart Could Save Your Real One. 2020. Available online: https://www.philips.com/a-w/about/news/archive/blogs/innovation-matters/20181112-how-a-virtual-heart-could-save-your-real-one.html (accessed on 16 June 2024).
Background Information. Erlang. 2018. Available online: www.siemens-healthineers.com (accessed on 16 June 2024).
Yakışan, B. Siemens Healthineers sağLıkta Geleceğin Teknolojilerini tanıTtı. Anadolu Ajansı. 2019. Available online: https://www.aa.com.tr/tr/sirkethaberleri/hizmet/siemens-healthineers-saglikta-gelecegin-teknolojilerini-tanitti-/654299 (accessed on 16 June 2024).
Price, L. Digital Health Hype Cycle 2020. Healthcare Digital. 2020. Available online: https://www.healthcare.digital/single-post/2020/01/29/Digital-Health-Hype-Cycle-2020 (accessed on 16 June 2024).
University of Amsterdam. Your Digital Twin: Closer Than You Think—Informatics Institute—University of Amsterdam. 2018. Available online: https://ivi.uva.nl/content/news/2018/04/your-digitaltwin.html?1556017299749 (accessed on 16 June 2024).
Dassault Systèmes’ Living Heart Project Reaches Next Milestones in Mission to Improve Patient Care. Dassault Systèmes. 2017. Available online: https://www.3ds.com/newsroom/press-releases/dassault-systemes-living-heart-project-reaches-next-milestones-mission-improve-patient-care (accessed on 16 June 2024). Dassault Systèmes.
D’Souza, K. Technology to Transform Lives: The SIMULIA Living Heart Model. 2015. Available online: https://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandToba (accessed on 16 June 2024).
Erol, T.; Mendi, A.F.; Doğan, D. The digital twin revolution in healthcare. In Proceedings of the 2020 4th International Symposium on Multidisciplinary Studies and Innovative Technologies (ISMSIT), Istanbul, Turkey, 22–24 October 2020; pp. 1–7. [ Google Scholar ]
Yuzyılın Saglık Trendleri GE Turkiye Blog. General Electric. 2016. Available online: https://geturkiyeblog.com/21-yuzyilin-saglik-trendleri/ (accessed on 16 June 2024).
Sooma Sooma TreatmentOutcomes (2018). Sooma. 2018. Available online: https://soomamedical.com/sooma-treatment-outcomes-2018/ (accessed on 16 June 2024).
Myontec MBody Shorts—Perform Better, Myontec. 2020. Available online: https://performbetter.co.uk/product/myontec-mbody-pro-portable (accessed on 16 June 2024).
Sun, T.; He, X.; Li, Z. Digital twin in healthcare: Recent updates and challenges. Digit. Health 2023 , 9 , 20552076221149651. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Moztarzadeh, O.; Jamshidi, M.; Sargolzaei, S.; Jamshidi, A.; Baghalipour, N.; Malekzadeh Moghani, M.; Hauer, L. Metaverse and Healthcare: Machine Learning-Enabled Digital Twins of Cancer. Bioengineering 2023 , 10 , 455. [ Google Scholar ] [ CrossRef ] [ PubMed ]
ISO/IEC 27001:2022 ; Information Security, Cybersecurity and Privacy Protection—Information Security Management Systems—Requirements, Edition 3. ISO: Geneva, Switzerland, 2022.
Vahdati, A. Cornea digital twins for studying the critical role of mechanics in physiology, pathology and surgical repair. In Digital Human Modeling and Medicine ; Academic Press: Cambridge, MA, USA, 2023; pp. 443–463. [ Google Scholar ]
Iliuţă, M.E.; Moisescu, M.A.; Caramihai, S.I.; Cernian, A.; Pop, E.; Chiş, D.I.; Mitulescu, T.C. Digital Twin Models for Personalised and Predictive Medicine in Ophthalmology. Technologies 2024 , 12 , 55. [ Google Scholar ] [ CrossRef ]
Armeni, P.; Polat, I.; De Rossi, L.M.; Diaferia, L.; Visioli, G.; Meregalli, S.; Gatti, A. Digital Twins for Health: Opportunities, Barriers and a Path Forward. In Digital Twin Technology—Fundamentals and Applications ; IntechOpen: Rijeka, Croatia, 2023. [ Google Scholar ]
Mitrofanova, Y.S.; Sherstobitova, A.A.; Filippova, O.A. Modeling smart learning processes based on educational data mining tools. In Smart Education and e-Learning 2019 ; Springer: Singapore, 2019; pp. 561–571. [ Google Scholar ]
Abdel-Basset, M.; Manogaran, G.; Mohamed, M.; Rushdy, E. Internet of things in smart education environment: Supportive framework in the decision-making process. Concurr. Comput. Pract. Exp. 2019 , 31 , e4515. [ Google Scholar ] [ CrossRef ]
Adu, E.K.; Poo, D.C. Smart learning: A new paradigm of learning in the smart age. In Proceedings of the International Conference on Teaching and Learning in Higher Education, Kuching, Malaysia, 11–13 April 2014. [ Google Scholar ]
Arantes, J. Digital twins and the terminology of “personalization” or “personalized learning” in educational policy: A discussion paper. Policy Futur. Educ. 2024 , 22 , 524–543. [ Google Scholar ] [ CrossRef ]
Chen, Y.; Zheng, Y.; Xue, T.; Lin, W.; Wen, J.; Chen, G. Harnessing the Synergy of Real Teacher, Digital Twin, and AI in Blended Metaverse Learning Environment: A Catalyst for Medical Education Reforms. 2024. Available online: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4745941 (accessed on 2 March 2024).
Khana, Z.H.; Mekida, S. Designing Remote Labs in Outcome Based Education using Digital Twin and Metaverse. Available online: https://www.researchgate.net/profile/Zeashan-Khan/publication/377928011_Designing_Remote_Labs_in_Outcome_based_Education_using_Digital_Twin_and_Metaverse/links/65bdd0801bed776ae3276058/Designing-Remote-Labs-in-Outcome-based-Education-using-Digital-Twin-and-Metaverse.pdf (accessed on 16 June 2024).
Sim, J.K.; Xu, K.W.; Jin, Y.; Lee, Z.Y.; Teo, Y.J.; Mohan, P.; Huang, L.; Xie, Y.; Li, S.; Liang, N.; et al. Designing an Educational Metaverse: A Case Study of NTUniverse. Appl. Sci. 2024 , 14 , 2559. [ Google Scholar ] [ CrossRef ]
Goodwin, T.; Xu, J.; Celik, N.; Chen, C.H. Real-time digital twin-based optimization with predictive simulation learning. J. Simul. 2024 , 18 , 47–64. [ Google Scholar ] [ CrossRef ]
Dietz, M.; Pernul, G. Digital twin: Empowering enterprises towards a system-of-systems approach. Bus. Inf. Syst. Eng. 2020 , 62 , 179–184. [ Google Scholar ] [ CrossRef ]
Priyanka, E.B.; Thangavel, S.; Gao, X.Z.; Sivakumar, N.S. Digital twin for oil pipeline risk estimation using prognostic and machine learning techniques. J. Ind. Inf. Integr. 2022 , 26 , 100272. [ Google Scholar ] [ CrossRef ]
Lu, H.; Guo, L.; Azimi, M.; Huang, K. Oil and Gas 4.0 era: A systematic review and outlook. Comput. Ind. 2019 , 111 , 68–90. [ Google Scholar ] [ CrossRef ]
Mohamed, N.; Al-Jaroodi, J.; Lazarova-Molnar, S. Leveraging the capabilities of industry 4.0 for improving energy efficiency in smart factories. IEEE Access 2019 , 7 , 18008–18020. [ Google Scholar ] [ CrossRef ]
Dong, B.; O’Neill, Z.; Li, Z. A BIM-enabled information infrastructure for building energy Fault Detection and Diagnostics. Autom. Constr. 2014 , 44 , 197–211. [ Google Scholar ] [ CrossRef ]
Modi, A.S. Review article on deep learning approaches. In Proceedings of the 2018 Second International Conference on Intelligent Computing and Control Systems (ICICCS), Madurai, India, 14–15 June 2018; pp. 1635–1639. [ Google Scholar ]
Barkwell, K.E.; Cuzzocrea, A.; Leung, C.K.; Ocran, A.A.; Sanderson, J.M.; Stewart, J.A.; Wodi, B.H. Big data visualization and visual analytics for music data mining. In Proceedings of the 2018 22nd International Conference Information Visualization (IV), Salerno, Italy, 10–13 July 2018; pp. 235–240. [ Google Scholar ]
Bibri, S.E.; Krogstie, J. The core enabling technologies of big data analytics and context-aware computing for smart sustainable cities: A review and synthesis. J. Big Data 2017 , 4 , 1–50. [ Google Scholar ] [ CrossRef ]
Deng, Z.; Huang, M.; Wan, N.; Zhang, J. The Current Development of Structural Health Monitoring for Bridges: A Review. Buildings 2023 , 13 , 1360. [ Google Scholar ] [ CrossRef ]
Huang, M.; Ling, Z.; Sun, C.; Lei, Y.; Xiang, C.; Wan, Z.; Gu, J. Two-stage damage identification for bridge bearings based on sailfish optimization and element relative modal strain energy. Struct. Eng. Mech. Int. J. 2023 , 86 , 715–730. [ Google Scholar ]
Zhang, J.; Huang, M.; Wan, N.; Deng, Z.; He, Z.; Luo, J. Missing measurement data recovery methods in structural health Monitoring: The State, challenges and case study. Measurement 2024 , 231 , 114528. [ Google Scholar ] [ CrossRef ]
Huang, M.; Zhang, J.; Hu, J.; Ye, Z.; Deng, Z.; Wan, N. Nonlinear modeling of temperature-induced bearing displacement of long-span single-pier rigid frame bridge based on DCNN-LSTM. Case Stud. Therm. Eng. 2024 , 53 , 103897. [ Google Scholar ] [ CrossRef ]
Xia, H.; Liu, Z.; Maria, E.; Liu, X.; Lin, C. Study on city digital twin technologies for sustainable smart city design: A review and bibliometric analysis of geographic information system and building information modeling integration. Sustain. Cities Soc. 2022 , 84 , 104009. [ Google Scholar ] [ CrossRef ]
Vuoto, A.; Funari, M.F.; Lourenço, P.B. Shaping digital twin concept for built cultural heritage conservation: A systematic literature review. Int. J. Archit. Herit. 2023 , 1–34. [ Google Scholar ] [ CrossRef ]
Vuoto, A.; Funari, M.F.; Lourenço, P.B. On the use of the digital twin concept for the structural integrity protection of architectural heritage. Infrastructures 2023 , 8 , 86. [ Google Scholar ] [ CrossRef ]
Zhang, X.; Shen, J.; Saini, P.K.; Lovati, M.; Han, M.; Huang, P.; Huang, Z. Digital twin for accelerating sustainability in positive energy district: A review of simulation tools and applications. Front. Sustain. Cities 2021 , 3 , 663269. [ Google Scholar ] [ CrossRef ]

Click here to enlarge figure

Authors	Year	Definition
Grives et al. [ ]	2016	“The Digital Twin theoretical model […] contains three main components: (a) real environment physical products (b) virtual products in virtual space, and (c) the information and data links which connects real and virtual products.”
Negri et al. [ ]	2017	“The Digital Twin is a production system virtual representation which can be executed on various simulation environments, through the synchronization between the real and virtual system, using mathematical models, appropriate information. connected intelligent devices and mathematical models.”
Autiosalo et al. [ ]	2018	“The DT is the cyber part of a cyber-physical system (CPS).”
Boschert et al. [ ]	2018	“The Digital Twin vision consists of a complex description at the functional and physical layer of a system, product or component, that integrates useful data, which can be of interest for all phases of the on-going and and subsequent life cycles.”
Thao et al. [ ]	2018	“Full DT should integrate five components: services, data, connections, virtual component and physical component.”
Zeng et al. [ ]	2018	“DT represents an integrated system which is able to monitor, simulate, regulate, compute and control the system’s process and status.”

Classification Criteria of DTs	Types of DTs	Selected References
Depending on the time of creation		[ ]
Depending on the integration level		[ ]
From the application point of view		[ ]
According to the parameters on which the application focuses		[ , ]
From a hierarchical point of view		[ , ]
Depending on the level of maturity		[ ]
Functional sophistication level of the virtual representation		[ ]

Digital Twin Capabilities	Technologies	Features
Data acquisition	IoT Sensors	Data format, enrichment, configuration
Information access API	Monitoring, interactions, engaging, control of the physical devices	Information access and processing, upon request
Deployment/simulation	Cloud Computing	Cloud-based DTs of manufacturing machines
Information model	Virtual/Augmented Reality	Optimization, quality assurance, testing
Security	Cyber-security	Role-based access control for authenticated users
Interoperability	5G, wireless connectivity	DT various information format
Synchronization	DT replicas correlated with adjacent architectural tiers	Data transmission between architectural tiers

Characteristics	Yuqian et al. [ ]	Alam et al. [ ]	Aheleroff et al. [ ]
Application Field	Smart manufacturing, convergence of digital and physical space	Cloud-based cyber-physical systems, telematics application	Industrial transformation, mass individualization
Technologies and methods used	Technologies for data processing and information model	Cloud computing, Bayesian network, fuzzy logic	Cloud computing, Internet of Things, augmented reality, ThingWorx, Vuforia
Key aspects	Data-driven smart manufacturing, smart decisions at every manufacturing point	Telematics-based driving assistance	Real-time monitoring, Remote controlling, Prediction
Architecture model	Proposes a reference model for DT in the context of smart manufacturing	Reference model for C2PS architecture	Adopts RAMI and an agile model for integrating different levels of DT
The relationship with Industry 4.0	Integrating DT in smart manufacturing operations	Integrating cloud computing and physical sensor level control	Use of Industry 4.0 technologies
Data source	Capturing information from physical devices and their integration into the manufacturing process	Capturing information from physical devices	Integration of data from various sources
Adaptability	Adaptability to varied production needs	Adaptability to environmental changes	Adaptability in deployment and integration
Security	Implementing security measures and controls in the context of smart manufacturing	Implementation and compliance with security strategies for data in Cloud	Use of security technologies in DTaaS
Interoperability	Compliance with ISO standards and compatibility with existing systems	Integration with other systems and compliance with standards	Agile approach for different levels of integration
Challenges and future research directions	Standardization of communication protocols, real-time data processing, timeliness and accuracy of models, reliability	Scalability and the realization of interactions between systems, integration with Blockchain and artificial intelligence	Integration levels, mass individualization, resilience of the Digital Twin

Applications of Digital Twins—Fields	References
A. Manufacturing	[ , , , , , , , , , , , , , , , , , , , , , , ]
B. Medicine	[ , , , , , , , , , , , , , , , , , , , , , , , , , ]
C. Various fields—Smart cities, Energy production, Oil industry, Education	[ , , , , , , , , , , , , , , , , , , , , , , , ]

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Iliuţă, M.-E.; Moisescu, M.-A.; Pop, E.; Ionita, A.-D.; Caramihai, S.-I.; Mitulescu, T.-C. Digital Twin—A Review of the Evolution from Concept to Technology and Its Analytical Perspectives on Applications in Various Fields. Appl. Sci. 2024 , 14 , 5454. https://doi.org/10.3390/app14135454

Iliuţă M-E, Moisescu M-A, Pop E, Ionita A-D, Caramihai S-I, Mitulescu T-C. Digital Twin—A Review of the Evolution from Concept to Technology and Its Analytical Perspectives on Applications in Various Fields. Applied Sciences . 2024; 14(13):5454. https://doi.org/10.3390/app14135454

Iliuţă, Miruna-Elena, Mihnea-Alexandru Moisescu, Eugen Pop, Anca-Daniela Ionita, Simona-Iuliana Caramihai, and Traian-Costin Mitulescu. 2024. "Digital Twin—A Review of the Evolution from Concept to Technology and Its Analytical Perspectives on Applications in Various Fields" Applied Sciences 14, no. 13: 5454. https://doi.org/10.3390/app14135454

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Changes in the attractiveness of medical careers and career determinants during the bachelor’s program at Zurich medical schools

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BMC Medical Education volume 24 , Article number: 693 ( 2024 ) Cite this article

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Monitoring the career intentions of medical students during their undergraduate studies could help to address the shortage of physicians, particularly in general practice. This study aimed to investigate changes in medical students' career openness, attractiveness and determinants of medical career choice during their bachelor’s studies.

The design was cross-sectional, recruiting all medical students who started a bachelor’s program in one of the four different educational tracks in Zurich, Switzerland, in the fall of 2019 (first survey) and completed it in the summer of 2022 (second survey). Students’ perceptions of the attractiveness and determinants of different medical career options were assessed using a structured online questionnaire. Absolute changes between the two-time points were reported in percentage points overall and by educational track. Regression analysis was used to examine the association of student characteristics and determinants of career options with the attractiveness of each option.

We surveyed 354 medical students at the beginning and 433 at the end of the bachelor’s program (participation rate: 71.1% and 86.9%, respectively). Overall, the proportion of students open to all proposed medical career options decreased (from 52.8% to 43.8%, p = 0.004). The attractiveness of outpatient gynecology or pediatrics increased (from 27.4% to 43.4%, p < 0.001), whereas the attractiveness of both general and specialized inpatient care decreased (from 47.8% to 40.3%, p = 0.05 and from 71.1% to 61.1%, p = 0.006 respectively). There was an increase in the proportion of students who perceived part-time work, autonomy and relationships with patients as important career determinants (from 47.3% to 64.7%, p < 0.001; from 63.3% to 77.8%, p < 0.001; from 80.8% to 89.3%, p = 0.002 respectively), while the importance of reputation and career opportunities decreased (from 42.6% to 26.2%, p < 0.001; from 79.2% to 63.6%, p < 0.001 respectively). The importance of part-time work and relationships with patients were positively associated with the attractiveness of general practice.

Conclusions

During the bachelor’s program, the attractiveness of a career in general practice tended to decrease, but the importance of part-time work, autonomy and relationships with patients as career determinants increased. Helping students understand how these determinants relate to general practice may increase their interest in the profession.

Trial registration

Not applicable.

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Medical students’ motivations for choosing their specialty are diverse and influenced by the socioeconomic context in which they live: students from high-income countries are often motivated by scientific and humanitarian reasons, while those from upper-middle and lower middle-income countries are also influenced by societal factors such as prestige or job security [ 1 ]. As global health care becomes more complex and medical careers evolve, understanding what makes medical careers attractive during medical education is essential to the maintenance, sustainability and effectiveness of healthcare systems worldwide.

Several factors influence medical students' career choices [ 2 ]. These include demographic variables such as age and gender [ 2 ], opportunities for entrepreneurship in different practice settings (e.g. employed in a hospital or self-employed in private practice), patient contact, income, academic opportunities [ 3 , 4 , 5 , 6 ], the medical curriculum as well as exposure to different medical specialties through clinical rotations [ 7 ] and the culture of the medical school itself [ 8 ]. During their studies, the emphasis on career determinants may shift from intrinsic motivations, such as personal values, self-confidence and a positive attitude towards patient care, to extrinsic factors, including status and reputation, working conditions, and experiences within specific specialties [ 2 ]. Gender also plays a role in shaping these motivations, with intrinsic motivations being more common among female students and extrinsic ones among male students [ 9 , 10 ].

Understanding all of these factors is essential to developing strategies to address local healthcare workforce challenges, which are also affected by the global health worker migration [ 11 ]. Primary care workforces are declining globally [ 12 , 13 ]. In Switzerland, this decline is of particular concern, as one in four physicians is 60 years of age or older and expected to retire within a few years, exacerbating the current workforce shortage [ 14 ]. General practitioners (GPs), who provide primary care, play a key role in most healthcare systems, making a shortage of GPs particularly problematic [ 15 , 16 ]. In Switzerland, as in many other countries, GPs are the first point of contact for patients and act as coordinators in the healthcare system. The majority of the Swiss population has a health insurance model that places GPs in a gatekeeping role and thus in an even more central position [ 17 ]. Unfortunately, it is also predicted that the GP workforce will continue to fall short of demand, as the number of GPs and pediatricians in Switzerland is expected to decrease by 8.4% by 2030 [ 18 , 19 , 20 ].

Therefore, to ensure that medical education adapts and meets the evolving needs of society and the healthcare system, it is necessary to make general practice a more attractive career choice for medical students [ 21 ].

Swiss medical education consists of two main levels: the bachelor's degree in Human Medicine and the master's degree in Human Medicine, both having a duration of three years. While the bachelor’s degree program focuses on a solid foundation in basic medical sciences and includes only introductory clinical skills training, the master’s degree focuses on clinical training, including rotations in various medical specialties. Swiss medical students are assigned to specific medical schools through a centralized and competitive admissions process designed to select candidates who are likely to complete medical school and to take into account regional distribution.

Given the dynamics of the medical workforce and societal demands, medical students’ career interests and intentions require monitoring. Therefore the present study, conducted at the University of Zurich, Switzerland, aimed to answer the following questions:

1) Do the career openness and attractiveness of different medical career options change during the bachelor’s program in medical education?

2) Does the importance of career determinants change during the bachelor’s program in medical education?

3) Which factors and career determinants are associated with the attractiveness of each medical career option?

Specifically, we aimed to evaluate student-perceived attractiveness of individual career options with a particular focus on general practice in comparison to other specialties. Previous studies have examined the stability of medical students’ career interests using two measures, typically at entry and exit of medical school [ 22 , 23 , 24 ]. With this study, we expected to provide further insights into aspects that should be considered in specific interventions in medical education to increase interest in general practice.

Design and participants

The study consisted of two rounds of a cross-sectional survey at the beginning and end of the bachelor's program, conducted in fall 2019 and summer 2022, among students enrolled in different medical education tracks at the University of Zurich: the largest track includes both a bachelor’s and a master’s degree and teaches medicine without an explicit teaching focus (Med General ); two other tracks are bachelor’s programs that begin at the University of Zurich and continue at the University of Lucerne or St. Gallen for the master's degree, with a focus on primary care (Med PrimCare ). An additional track is located at the Swiss Federal Institute of Technology and is a bachelor’s program followed by a master's program at the University of Basel, Lugano or Zurich, with a stronger focus on research and technology (Med ResTech ) [ 25 , 26 ]. The same questionnaire was used in both rounds and was specifically designed for the purposes of this study. The first round took place during a plenary lecture. Methods, definitions and results of the first survey have been published [ 27 ]. Since attendance at lectures was lower in the third year, the second round was conducted by inviting students via email or chat groups, with a reminder email and a raffle among survey participants (prizes were 10 vouchers valued at CHF 100 each to spend in a store chosen by the winner).

Questionnaire

The questionnaire at both time points was in German and included items measuring the attractiveness of different medical career options and the importance of determinants of career choice. An English translation of the survey is available [ 27 ]. The attractiveness of seven proposed specific or aggregated medical career options (general practice, outpatient gynecology/pediatrics, specialized outpatient care other than gynecology/pediatrics, inpatient general internal medicine, specialized inpatient care, academic, medical technology industry) was measured on a five-point Likert scale (from “excluded goal” to “the only goal”). Similarly, a five-point Likert scale (from “not at all important” to “very important”) was used to rate the perceived importance of eight career determinants (relationship with patients, primarily performing medical activities, autonomy, part-time work, career opportunities, income, reputation, political context) which have been identified in the literature as potentially important [ 2 , 3 , 4 , 5 , 6 ]. The questionnaire also included information on the medical education track attended, demographic characteristics (place of residence, gender, age) and the score obtained in the mandatory and selective aptitude test [ 27 ] upon entry to the medical education program.

This study did not fall within the scope of the Swiss Human Research Act, as no health-related data were used [ 28 ] and was therefore not subject to approval by the local ethical committee. Approval was obtained from the respective universities. Participation in the survey was voluntary and participants were informed and agreed that their data would be collected, summarized and published anonymously.

Study outcomes

Study outcomes were changes during the bachelor’s program in the percentage of students who: 1) perceived complete openness to all proposed medical career options; 2) perceived a proposed medical career option as attractive; 3) rated a proposed determinant of career choice as important. Outcomes were assessed both in the total population and within education tracks. Furthermore, we assessed the association of student characteristics and the perceived importance of career determinants with the attractiveness of specific career options.

In terms of career openness, respondents were categorized as being: “completely open” to all proposed career options if they did not rate any of the proposed career options as ‘the only goal’ or as ‘an excluded goal’; “committed” if they rated any of the proposed career options as “the only goal”; “partially open” if they did not rate any career option as “the only goal” but at least one as “excluded goal”. Regarding the attractiveness of career options, respondents were categorized as perceiving a proposed career as “attractive” if they rated the career as “rather attractive” or “the only goal”. Regarding the importance of the determinants of career choice, respondents were categorized as perceiving a proposed determinant as “important” if they rated it as “rather important” or “very important”.

Statistical analysis

Statistical analysis was performed using the R software (version 4.1.0) [ 29 ]. Student characteristics and measurements at the two-time points were described as numbers and percentages, n(%), for categorical or binary variables and as mean (standard deviation (SD)) or median [interquartile range (IQR)], as appropriate, for continuous variables. Available case analysis was performed and the number of non-missing observations was reported. For group comparisons between the two time points, chi-squared test was used for categorical or binary variables and t-test or Wilcoxon test, as appropriate, for continuous variables. The attractiveness of medical career options and the importance of career determinants as a five-point Likert scale at the two-time points were presented graphically using a diverging bar chart. Study outcomes 2) and 3), as described above, were presented using a dumbbell plot, also known as a connected dot plot, with additional reporting of absolute differences with 95% confidence interval and p -value from chi-square test. For all analyses, students from the two Med PrimCare tracks were combined into a single track, as they both focused on aspects of primary care. Logistic regression analysis, multivariable and univariable, was carried out to identify student characteristics and career determinants associated with the attractiveness of each medical career option. An additional multivariable logistic analysis was carried out to examine the association between student characteristics and the importance of career determinants. The selection of variables for multivariable models was based on a stepwise backward approach, starting from a full model including all variables and excluding them using the Akaike information criterion (AIC). The results of regression analyses were reported as odds ratios (OR) with 95% confidence intervals. The final model results were presented in a forest plot. Due to the pre-specified number of observed cases, no power calculation was performed. A p ≤ 0.05 was used to determine statistical significance.

Population characteristics

In the first-year survey, a total of 354 medical students participated (Med General 201, Med PrimCare 59, Med ResTech 94) and the overall participation rate was 71.1% (participation rates 67.0%, 67.0% and 85.5% respectively). In the third year, 433 medical students participated (Med General 269, Med PrimCare 83, Med ResTech 81) and the overall participation rate was 86.9% (Med General 89.7%, Med PrimCare 94.3%, Med ResTech 73.6%). Participants were predominantly female, with n = 199 (64.8%) in the first year and n = 281 (66.0%) in the third year, with a mean age of 20.2 years (SD = 2.2) in the first year and 22.9 years (SD = 2.2) in the third year. All student characteristics are described in Table 1 .

Changes in career openness

The percentage of students who perceived themselves as completely open to all proposed career options decreased from 52.8% in the first year to 43.8% in the third year, but the percentage of students who perceived themselves as committed to a career also decreased from 17.0% to 14.2%, p = 0.004. The same trend was observed in the Med General track, where openness decreased from 56.1% to 41.6% and commitment from 13.5% to 11.2%, p = 0.002 (Table 1 ).

Changes in the attractiveness of career options

There were significant changes during the bachelor’s program in the attractiveness of three of the seven proposed career options (see Fig. 1 , results in Likert scales, and Fig. 2 , results in percentages and absolute differences between the two-time points, overall and at the level of the medical education tracks). A strong increase in attractiveness was observed in outpatient gynecology/pediatrics (from 27.4% in the first year to 43.4% in the third year, p < 0.001). At the same time, the attractiveness of inpatient care disciplines decreased significantly (inpatient general internal medicine: from 47.8% to 40.3%, p = 0.05; specialized inpatient care: from 71.1% to 61.1%, p = 0.006). Nevertheless, specialized medical career options, both outpatient and inpatient, continued to outrank inpatient general internal medicine or general practice. The attractiveness of general practice did not change. We observed, in addition, that among the students who found general practice attractive, the proportion of students who also found other specialties attractive increased during the bachelor’s program.

Attractiveness of medical career options during the bachelor’s program. Survey results (Likert-scale) at the beginning (first year) and at the end (third year) of medical school (bachelor’s program). The right side shows the percentages of positive responses (rather attractive/the only goal). In the middle are the percentages of neutral responses, and on the left are the percentages of negative responses (excluded goal/not very attractive)

Changes in the attractiveness of medical career options during the bachelor’s program. Absolute differences, overall and by track, in the percentage of medical students attracted to each specialty at the two time-points, at the beginning (first year) and at the end (third year) of the bachelor’s program, are reported with 95% confidence interval and p -values. Third-year observations are indicated by arrowheads to highlight the direction. CI: confidence interval; Med General : medical education track without specific focus; Med PrimCare : medical education track with a focus on primary care; Med ResTech medical education track with a focus on research and technology

Changes in determinants of career choice

There were significant changes during the bachelor’s program in five of the eight proposed determinants of career choice (see Fig. 3 , results in Likert scales, and Fig. 4 , results in percentages and absolute differences between the two-time points, overall and at the level of the medical education tracks). The largest change was an increase in the perceived importance of part-time work (from 47.3% in the first year to 64.7% in the third year, p < 0.001), followed by an increase in the importance of autonomy (from 63.3% to 77.8%, p < 0.001) and the relationship with patients (from 80.8% to. 89.3%, p = 0.002). On the other hand, there was a decrease in the importance of reputation (from 42.6% to 26.2%, p < 0.001) and career opportunities (from 79.2% to 63.6%, p < 0.001). These trends were confirmed by multivariable analysis, which also adjusted for sex and medical education track (Additional file 1 Table 1). At the level of medical education tracks, all these trends were observed in the Med General track and only the trends for autonomy and reputation in the Med PrimCare track, although they were not confirmed by multivariable analysis. There were no statistically significant changes in the career determinants within the Med ResTech track. In addition, after correcting for time effect and medical education track, male students were more likely than female students to value reputation and career opportunities, but less likely to rate part-time work and relationships with patients as important determinants of career choice.

Importance of career determinants during the bachelor’s program. Survey results (Likert-scale) at the beginning (first year) and at the end (third year) of medical school (bachelor’s program). The right side shows the percentages of positive responses (rather important/very important). In the middle are the percentages of neutral responses, and on the left are the percentages of negative responses (not at all important/rather not important)

Changes in the importance of career determinants during the bachelor’s program. Absolute differences, overall and by track, in the percentage of medical students rating each factor as important at both time points, at the beginning (first year) and at the end (third year) of the bachelor’s program, are reported with 95% confidence intervals and p -values. Third-year observations are indicated by arrowheads to highlight the direction. CI: confidence interval; Med General : medical education track without specific focus; Med PrimCare : medical education track with a focus on primary care; Med ResTech medical education track with a focus on research and technology

Factors associated with the attractiveness of medical career options

The trends observed in the attractiveness of each medical career option, as shown in Fig. 2 , were assessed by multivariable analysis. In Fig. 5 , results of the final best-performing multivariable models for the attractiveness of each career option are reported (see Additional file 1 Table 2 for univariable analysis and alternative second-best models). The adjusted analysis confirmed the positive trend in the attractiveness of outpatient gynecology/pediatrics during the bachelor’s program, OR (95% CI): 1.92 (1.35, 2.73) for a third-year student compared to a first-year student, and evidenced a positive trend also in the other specialized outpatient disciplines, 1.44 (1.05, 1.98), but a negative trend in the attractiveness of general practice, 0.64 (0.45, 0.91). In addition, there were factors associated with the attractiveness of only one or more career options. The importance of part-time work was positively associated with the attractiveness of a career in general practice, outpatient gynecology/pediatrics or inpatient general internal medicine, but negatively associated with a career in specialized inpatient care. The importance of career opportunities was positively associated with the attractiveness of a career in the specialized disciplines (outpatient and inpatient) or the research-oriented career options (academic or medical technology industry), but negatively associated with the attractiveness of general practice. Being male was positively associated with the attractiveness of a career in outpatient specialties other than gynecology/pediatrics, but negatively associated with the attractiveness of a career in outpatient gynecology/pediatrics. Rating the performance of medical activities as important was positively associated with the attractiveness of a career in inpatient general internal medicine, but negatively associated with the attractiveness of a career in outpatient specialties other than gynecology/pediatrics or in the research-oriented career options. Studying in the Med ResTech track was positively associated with the attractiveness of the research-oriented career options. The importance of autonomy was only positively associated with a research-oriented career in medical technology industry. The importance of the relationship with patients and the political context were uniquely associated, positively and negatively respectively, with the attractiveness of general practice. The importance of income was only positively associated with the attractiveness of specialized outpatient care other than gynecology/pediatrics. The importance of reputation was only positively associated with the attractiveness of a career in specialized inpatient care.

Logistic multivariable regression models (forest plot) of the attractiveness of medical career options. Odds ratios are reported with 95% confidence intervals and p -values. OR: odds ratio; CI: confidence interval

This study examined changes in medical students' career openness and changes in the perceived attractiveness of career options during the bachelor's program at the University of Zurich and the factors associated with these perceptions. We found that career openness decreased during the bachelor’s program, suggesting that students were already in the process of narrowing their career options. The perceived importance of medical career determinants changed significantly, with an overall increase in the importance of part-time work, autonomy and relationship with patients, and a decrease in the importance of reputation and career opportunities. Multivariable analysis showed that the importance of part-time work was positively associated with the attractiveness of general practice, outpatient gynecology/pediatrics and inpatient general internal medicine, although there was a negative trend in the attractiveness of general practice as a career option during the bachelor’s program whereas the attractiveness of outpatient specialized care increased.

This study found that the percentage of students who were completely open to a career decreased during the bachelor’s program, but interestingly, the percentage of students who had committed to a specific medical career also decreased. As a result, there was an increase in the proportion of partially open students, i.e. students who had excluded a particular medical career as a goal without committing to any other specific career. This is consistent with previous studies showing that career intentions are rarely fixed [ 30 , 31 , 32 ] but that the proportion of completely undecided students decreases over time [ 30 ].

Changes in attractiveness of medical career options and career determinants

In our study, the majority of students perceived a career in a specialized care setting (both inpatient and outpatient) as most attractive throughout the observation period and the attractiveness of outpatient gynecology/pediatrics increased significantly (mainly observed in the Med General education track). These findings are consistent with the literature, although a direct comparison is not possible due to differences in the specialty definition between studies [ 24 , 33 , 34 ]. Moreover, longitudinal studies found that the most stable career intentions were general practice and internal medicine and the least stable were pediatrics and obstetrics-gynecology [ 22 , 24 ]. In our study, one in three students appeared to be interested in a career in general practice and there was no change observed over time. Previous research found similar numbers regarding the percentage of students interested in general practice at the end of the bachelor’s program [ 35 ], but differently from our study, the attractiveness of general practice increased during the bachelor’s program. Furthermore, in our multivariable analysis, a student was less likely to be interested in general practice at the end of the bachelor’s program than at the beginning. This negative trend was also observed in another study [ 36 ].

In terms of changes in determinants of career choice, we observed a significant increase in the importance of part-time work, autonomy and relationships with patients. These factors contribute to GPs’ work satisfaction in clinical practice [ 37 ] and (except for autonomy) were associated with the attractiveness of general practice in our study. Despite the overall negative trend in the attractiveness of general practice, these determinants were rated most highly by the Med PrimCare track students’, which may indicate that these students may become more interested in a career in general practice later in their medical education.

Factors associated with the attractiveness of medical career options and career determinants

The perceived attractiveness of different career options depends on student-sided factors and the importance of determinants which we modelled using logistic regression analysis. We found that perceiving part-time as important was positively associated with the attractiveness of general practice, outpatient gynecology/pediatrics and inpatient general internal medicine, as previous studies have shown [ 38 , 39 , 40 ]. Consistent with our findings, many medical students who narrow their careers show a preference for part-time work, with a significantly higher proportion of female students compared to their male counterparts [ 9 , 41 , 42 , 43 ]. In addition, our finding that being female is positively associated with the attractiveness of gynecology/pediatrics is also supported by the literature [ 44 , 45 , 46 , 47 , 48 , 49 ]. Moreover, we found a positive association between the importance of income and the attractiveness of specialized outpatient care, also consistent with recent findings [ 13 ]. Furthermore, students rating career opportunities as important were more likely to be attracted to specialized care (both outpatient and inpatient) or research (both academic and industry). Similar results have been found in previous studies [ 9 , 13 , 50 , 51 ], but no previous study has analyzed research as a distinct career option. Interestingly, there were factors that were uniquely associated with the attractiveness of general practice, i.e. perceiving relationships with patients as important and perceiving the political context as unimportant. The second factor is understandable in the context of the Swiss healthcare system, where general practice is less politically regulated than other medical disciplines [ 52 ]. These results are in line with previous findings that general practice is recognized by students for long-term patient relationships and patient contact [ 3 , 9 , 13 , 50 , 53 ] and that the influence of the medico-political climate is the most negative influencing factor associated with the attractiveness of a career in general practice [ 53 ]. In addition, other factors associated with the attractiveness in general practice include the perception of independent decision-making [ 13 ], the importance of work-family balance [ 13 , 53 ] and quality of life [ 3 ], better practical experiences in general practice during medical school [ 13 ] and the opinion that general practice provides a pleasant working environment [ 35 ].

Strengths and limitations

The strengths of this study are a high response rate (71% and 87% in the first and second surveys, respectively), which represents the majority of the target population. A novelty of the study is the inclusion of research as a distinct medical career option and its relative multivariable analysis. This is important because such research-oriented students, particularly in the industrial sector, could be lost to the physician workforce, thus reducing the effectiveness of medicals schools in mitigating predicted workforce shortages.

The main limitations of this study are the anonymous nature of the data collection, which did not allow the analysis of changes in individual respondents (hence the use of a repeated cross-sectional design) and the observational design, which prevented causal inference. Furthermore, we only examined the bachelor’s program, which is half of all medical school education. As career intentions during the first three years are only moderately predictive of final medical career choices, the cohort requires further follow-up [ 54 ]. It should be noted that we observed changes in the attractiveness of medical career options during the bachelor’s program, which we were able to explain using multivariate analysis, but without capturing all confounding factors. In fact, we don’t have information about the factors that determine students’ indirect exposure to a career or the “hidden curriculum” [ 13 , 53 ], such as advice, opinions or influences beyond what was formally or intentionally taught, from GPs or doctors from other specialties encountered in medical school, or advice from friends or classmates. Finally, it must be acknowledged that the educational tracks, especially Med PrimCare , are of limited size and, therefore, of limited power to detect small changes and differences.

Implications for research and practice

The study is relevant to the medical education provision and then to society, as it examines the career intentions of students at the beginning and end of their medical bachelor’s studies in different educational tracks. Although it is country-specific and depends on the curricula of specific medical schools as well as on the career opportunities, healthcare and political system in Switzerland, its findings are consistent with the global trend, particularly regarding the importance of work-life balance as a career determinant [ 48 ]. This may have potential implications for promoting certain career choices, such as general practice, where there are shortages. As one in three students in our study appeared to be interested in a career in general practice at the end of the bachelor’s program, this could mean that one in ten students would definitely choose to become a GP, based on previous estimates [ 22 , 53 ]. Although there is reason to believe that the attractiveness of general practice to students will increase with more direct exposure to general practice and its role model during their master’s studies [ 55 , 56 , 57 ], the main message of the study is to address the challenge of making primary care more attractive to students starting from the bachelor’s program. In fact, a third-year medical student was less likely to be interested in general practice compared to a first-year student. This requires special attention and further research. This might be due to an increased interest in other specialties, as the proportion of students who also found other specialties attractive was higher among third-year students than among first-year students, or to a negative perception of the general practice career or a misconception of the profession, as reported in the literature [ 13 ]. As in Switzerland GPs do not have their own specialty qualification like GPs in other European countries [ 58 ], medical students may not be aware of the specific skills and values of the profession and therefore need more guidance and support to develop positive attitudes towards the profession. For example, GP-specific perspectives and teaching during the bachelor’s program, based on case vignettes that address important determinants of general practice, such as the relationship with the patient, continuity of care, autonomy and independent decision making, and highlight that the profession allows for work-life balance and part-time work, would make students more familiar with the profession and perhaps more interested in choosing it as a career. In fact, students’ career interests are likely to be influenced by familiarity with a career and understanding of the profession’s role within the healthcare system [ 24 ]. In addition, given the evidence that societal needs influence career choices [ 8 , 59 , 60 , 61 ], medical schools should better inform students about the reality of workforce requirements and raise awareness of the need for more general practitioners. Improving the promotion of general practice in medical schools by introducing curricular experiences of general practice, such as practice visits or placements, is known to increase attractiveness [ 62 , 63 ]. Introducing early and meaningful exposure to general practice through clinical rotations and interactions with GPs could enhance the attractiveness of this career path [ 64 ] and positively influence students' career choices [ 65 ]. Long and immersive placements are even suggested and undergraduate primary care exposure should challenge students, testing not only their communication skills but also their clinical reasoning, diagnostic, ethical, and management competences [ 66 ]. In Austria an expanded four-semester curriculum for general practice within the ordinary medical school was introduced [ 13 ] to increase the orientation of graduates towards the GP profession. In Switzerland, the introduction of a specialist qualification for GPs could make general practice more attractive by giving the profession the same status as other qualifications. In addition, an adequate representation of general practice in medical schools might improve the reputation of general practice also within academic research, providing students with more research opportunities and therefore increasing their interest in the career [ 35 ].

Our results highlight the importance of part-time work, autonomy and patient contact as career determinants. Health policymakers should give priority to these aspects when undertaking measures to improve the working environment in primary care. Promoting part-time options and flexible working models could make general practice more interesting [ 13 ].

Further research, including longitudinal studies, is needed to track changes in career preferences over time and to understand the impact of early educational interventions on the attractiveness of general practice, compared with the other career options. This would help to design medical curricula that align with healthcare workforce needs. Additionally, comparative studies between different medical schools and educational tracks can identify best practices and highlight successful strategies for promoting a career in primary care.

Understanding what makes a career in medicine attractive at the undergraduate level is essential for adapting medical education to the evolving needs of society and the healthcare system, particularly to address the shortage of general practitioners. During the bachelor’s program, the attractiveness of a career in general practice tended to decrease, although interest in other specialties increased. Given the increased perception of the importance of part-time work, autonomy, and patient contact as career determinants, our findings suggest that informing students about the compatibility of these determinants with a career in general practice may increase their interest in the career.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

General practitioner(s)

Standard deviation

Interquartile range

Confidence interval

Goel S, Angeli F, Dhirar N, Singla N, Ruwaard D. What motivates medical students to select medical studies: a systematic literature review. BMC Med Educ. 2018;18(1):16.

Article Google Scholar

Querido SJ, Vergouw D, Wigersma L, Batenburg RS, De Rond ME, Ten Cate OT. Dynamics of career choice among students in undergraduate medical courses. A BEME systematic review: BEME Guide No. 33. Med Teach. 2016;38(1):18–29.

Lefevre JH, Roupret M, Kerneis S, Karila L. Career choices of medical students: a national survey of 1780 students. Med Educ. 2010;44(6):603–12.

Puertas EB, Arósquipa C, Gutiérrez D. Factors that influence a career choice in primary care among medical students from high-, middle-, and low-income countries: a systematic review. Rev Panam Salud Publica. 2013;34(5):351–8.

Google Scholar

Kinouani S, Boukhors G, Luaces B, Durieux W, Cadwallader JS, Aubin-Auger I, et al. Private or salaried practice: how do young general practitioners make their career choice? A qualitative study. BMC Med Educ. 2016;16(1):231.

Naimer S, Press Y, Weissman C, Zisk-Rony RY, Weiss YG, Tandeter H. Medical students’ perceptions of a career in family medicine. Isr J Health Policy Res. 2018;7(1):1.

Pfarrwaller E, Sommer J, Chung C, Maisonneuve H, Nendaz M, Junod Perron N, et al. Impact of interventions to increase the proportion of medical students choosing a primary care career: a systematic review. J Gen Intern Med. 2015;30(9):1349–58.

Bland CJ, Meurer LN, Maldonado G. Determinants of primary care specialty choice: a non-statistical meta-analysis of the literature. Acad Med. 1995;70(7):620–41.

Diderichsen S, Johansson EE, Verdonk P, Lagro-Janssen T, Hamberg K. Few gender differences in specialty preferences and motivational factors: a cross-sectional Swedish study on last-year medical students. BMC Med Educ. 2013;13:39.

Vaglum P, Wiers-Jenssen J, Ekeberg O. Motivation for medical school: the relationship to gender and specialty preferences in a nationwide sample. Med Educ. 1999;33(4):236–42.

Eaton J, Baingana F, Abdulaziz M, Obindo T, Skuse D, Jenkins R. The negative impact of global health worker migration, and how it can be addressed. Public Health. 2023;225:254–7.

Bein B. AAFP’s new physician workforce report represents “blueprint for change.” Ann Fam Med. 2010;8(1):86–7.

Mahlknecht A, Engl A, Barbieri V, Bachler H, Obwegeser A, Piccoliori G, et al. Attitudes towards career choice and general practice: a cross-sectional survey of medical students and residents in Tyrol, Austria. BMC Med Educ. 2024;24(1):294.

Hostettler S, Kraft E. Jeder vierte Arzt ist 60 Jahre alt oder älter. Schweizerische Ärztezeitung. 2021;103(13):414–9.

Tandjung R, Ritter C, Haller DM, Tschudi P, Schaufelberger M, Bischoff T, et al. Primary care at Swiss universities–current state and perspective. BMC Res Notes. 2014;7:308.

Tandjung R, Hanhart A, Bärtschi F, Keller R, Steinhauer A, Rosemann T, et al. Referral rates in Swiss primary care with a special emphasis on reasons for encounter. Swiss Med Wkly. 2015;145:w14244.

Studer C. Das Hausarztmodell in der Schweiz beschrieben am Beispiel des Ärztenetzes mediX luzern [The general practitioner model in Switzerland described using the example of the doctor network mediX luzern]. Z Evid Fortbild Qual Gesundhwes. 2023;181:98–100.

Chung C, Maisonneuve H, Pfarrwaller E, Audétat MC, Birchmeier A, Herzig L, et al. Impact of the primary care curriculum and its teaching formats on medical students’ perception of primary care: a cross-sectional study. BMC Fam Pract. 2016;17(1):135.

Cerny T, Rosemann T, Tandjung R, Chmiel C. Ursachen des Hausärztemangels - ein Vergleich zwischen Frankreich und der Schweiz [Reasons for General Practitioner Shortage – a Comparison Between France and Switzerland]. Praxis (Bern 1994). 2016;105(11):619–36.

Zeller A, Giezendanner S. Resultate der 4. Workforce studie. Prim Hosp Care Allg Inn Med. 2020;20(11):325–8.

Boelen C, Pearson D, Kaufman A, Rourke J, Woollard R, Marsh DC, Gibbs T. Producing a socially accountable medical school: AMEE Guide No. 109. Med Teach. 2016;38(11):1078–91.

Compton MT, Frank E, Elon L, Carrera J. Changes in U.S. medical students’ specialty interests over the course of medical school. J Gen Intern Med. 2008;23(7):1095–100.

Kassebaum DG, Szenas PL. Medical students’ career indecision and specialty rejection: roads not taken. Acad Med. 1995;70(10):937–43.

Scott I, Gowans M, Wright B, Brenneis F. Stability of medical student career interest: a prospective study. Acad Med. 2012;87(9):1260–7.

Weissmann Y, Wolfrum C, Goldhahn J. Humanmedizin an der ETH Zürich [Bachelor of Human Medicine at the ETH Zurich. A Contribution to the Training of Tomorrow’s Physicians]. Praxis (Bern 1994). 2020;109(11):853–8.

Gysin S, Schirlo C, Babst R. Joint Master Medizin Universität Luzern und Universität Zürich [Joint Medical Master University of Lucerne and University of Zurich]. Praxis (Bern 1994). 2020;109(11):847–52.

Markun S, Tandjung R, Rosemann T, Scherz N, Senn O. Attractiveness of medical disciplines amongst Swiss first-year medical students allocated to different medical education tracks: cross-sectional study. BMC Med Educ. 2022;22(1):252.

Federal Act on Research involving Human Beings. Fedlex. 2011. https://www.fedlex.admin.ch/eli/cc/2013/617/en . Accessed 24 Jan 2024.

R-Core-Team. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing. Vienna, Austria. 2023. https://www.r-project.org/ . Accessed 24 Jan 2024.

Pfarrwaller E, Voirol L, Karemera M, Guerrier S, Baroffio A. Dynamics of career intentions in a medical student cohort: a four-year longitudinal study. BMC Med Educ. 2023;23(1):131.

Vo A, McLean L, McInnes MDF. Medical specialty preferences in early medical school training in Canada. Int J Med Educ. 2017;8:400–7.

Pfarrwaller E, Voirol L, Piumatti G, Karemera M, Sommer J, Gerbase MW, et al. Students’ intentions to practice primary care are associated with their motives to become doctors: a longitudinal study. BMC Med Educ. 2022;22(1):30.

Grasreiner D, Dahmen U, Settmacher U. Specialty preferences and influencing factors: a repeated cross-sectional survey of first- to sixth-year medical students in Jena, Germany. BMC Med Educ. 2018;18(1):103.

Saadé S, Delafontaine A, Cattan J, Celanie D, Saiydoun G. Attractiveness and gender dynamics in surgical specialties: a comparative analysis of French medical graduates (2017–2022). BMC Med Educ. 2024;24(1):197.

Pols DHJ, Kamps A, Runhaar J, Elshout G, van Halewijn KF, Bindels PJE, et al. Medical students’ perception of general practice: a cross-sectional survey. BMC Med Educ. 2023;23(1):103.

Kruschinski C, Wiese B, Hummers-Pradier E. Attitudes towards general practice: a comparative cross-sectional survey of 1st and 5th year medical students. GMS Z Med Ausbild. 2012;29(5):Doc71.

Le Floch B, Bastiaens H, Le Reste JY, Lingner H, Hoffman RD, Czachowski S, et al. Which positive factors determine the GP satisfaction in clinical practice? A systematic literature review. BMC Fam Pract. 2016;17(1):133.

Heiligers PJM. Gender differences in medical students’ motives and career choice. BMC Med Educ. 2012;12(1):82.

Nieman LZ, Gracely EJ. Where nontradition is the norm: are sex and age determinants of practicing primary care specialties? J Womens Health Gend Based Med. 1999;8(7):967–72.

Gjessing S, Guldberg TL, Risør T, Skals RG, Kristensen JK. Would you like to be a general practitioner? Baseline findings of a longitudinal survey among Danish medical trainees. BMC Med Educ. 2024;24(1):111.

Drinkwater J, Tully MP, Dornan T. The effect of gender on medical students’ aspirations: a qualitative study. Med Educ. 2008;42(4):420–6.

Sanfey HA, Saalwachter-Schulman AR, Nyhof-Young JM, Eidelson B, Mann BD. Influences on medical student career choice: gender or generation?. Arch Surg. 2006;141(11):1086–94.

Johansson EE, Hamberg K. From calling to a scheduled vocation: Swedish male and female students’ reflections on being a doctor. Med Teach. 2007;29(1):e1-8.

Amudhan AS, Palaniyandi A, Rajan M, Parthiban P, Rajendraprasath S, Saminathan T, et al. The driving factors important for evaluation student’s opinion which influenced decision making of career choice: pediatrics as a career choice as an example. Acta Inform Med. 2021;29(2):94–8.

Bittaye M, Odukogbe A-TA, Nyan O, Jallow B, Omigbodun AO. Medical students’ choices of specialty in The Gambia: the need for career counseling. BMC Med Educ. 2012;12(1):72.

Burkhardt J, DesJardins S, Gruppen L. Diversity of the physician workforce: Specialty choice decisions during medical school. PLoS ONE. 2021;16(11):e0259434.

Khader Y, Al-Zoubi D, Amarin Z, Alkafagei A, Khasawneh M, Burgan S, et al. Factors affecting medical students in formulating their specialty preferences in Jordan. BMC Med Educ. 2008;8(1):32.

Levaillant M, Levaillant L, Lerolle N, Vallet B, Hamel-Broza JF. Factors influencing medical students’ choice of specialization: A gender based systematic review. EClinicalMedicine. 2020;28:100589.

Martinez S, Rrapi E, Hacker MR, Nguyen M, Jeffe DB, Capellan A, McKinney S. Student intentions to pursue obstetrics and gynecology training and practice in underserved areas. Am J Obstet Gynecol. 2023;228(2):242-6.e2.

Kiolbassa K, Miksch A, Hermann K, Loh A, Szecsenyi J, Joos S, et al. Becoming a general practitioner–which factors have most impact on career choice of medical students? BMC Fam Pract. 2011;12:25.

Yang Y, Li J, Wu X, Wang J, Li W, Zhu Y, Chen C, Lin H. Factors influencing subspecialty choice among medical students: a systematic review and meta-analysis. BMJ Open. 2019;9(3):e022097.

Cartier T, Senn N, Cornuz J, Bourgueil Y. Switzerland. 2015. In: building primary care in a changing Europe: case studies [Internet]. Internet: European Observatory on Health Systems and Policies (Observatory Studies Series, No. 40.) 29. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459012/ . Accessed 24 Mar 2024.

Barber S, Brettell R, Perera-Salazar R, Greenhalgh T, Harrington R. UK medical students’ attitudes towards their future careers and general practice: a cross-sectional survey and qualitative analysis of an Oxford cohort. BMC Med Educ. 2018;18(1):160.

Cantone RE, Deiorio NM, Polston A, Schneider B. Specialty choice stability: are there implications for early entry into residency?. PRiMER. 2018;2:30.

Burack JH, Irby DM, Carline JD, Ambrozy DM, Ellsbury KE, Stritter FT. A study of medical students’ specialty-choice pathways: trying on possible selves. Acad Med. 1997;72(6):534–41.

Kutob RM, Senf JH, Campos-Outcalt D. The diverse functions of role models across primary care specialties. Fam Med. 2006;38(4):244–51.

Scherz N, Markun S, Aemissegger V, Rosemann T, Tandjung R. Internists’ career choice towards primary care: a cross-sectional survey. BMC Fam Pract. 2017;18(1):52.

Badinella Martini M, Garattini L, Nobili A, Mannucci PM. Why so many different specialty training programmes in general practice in Europe?. Intern Emerg Med. 2022;17(7):1851–4.

Mutha S, Takayama JI, O’Neil EH. Insights into medical students’ career choices based on third- and fourth-year students’ focus-group discussions. Acad Med. 1997;72(7):635–40.

Kassebaum DG, Szenas PL, Schuchert MK. Determinants of the generalist career intentions of 1995 graduating medical students. Acad Med. 1996;71(2):198–209.

Kassler WJ, Wartman SA, Silliman RA. Why medical students choose primary care careers. Acad Med. 1991;66(1):41–3.

Nicholson S, Hastings AM, McKinley RK. Influences on students’ career decisions concerning general practice: a focus group study. Br J Gen Pract. 2016;66(651):e768–75.

Yeoh A, Sathiakumar AK, Leung CNY, Hoffman R, Gosbell A, Tan KN. Impact of clinical placement sites on general practice as a career preference for Australian medical students. Aust J Rural Health. 2022;30(1):95–102.

Shadbolt N, Bunker J. Choosing general practice - a review of career choice determinants. Aust Fam Physician. 2009;38(1–2):53–5.

Marchand C, Peckham S. Addressing the crisis of GP recruitment and retention: a systematic review. Br J Gen Pract. 2017;67(657):e227–37.

McDonald P, Jackson B, Alberti H, Rosenthal J. How can medical schools encourage students to choose general practice as a career?. Br J Gen Pract. 2016;66(647):292–3.

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Acknowledgements

The authors wish to thank all students participating in the study.

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Katja Weiss and Stefania Di Gangi shared first authorship.

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Institute of Primary Care, University of Zurich and University Hospital of Zurich, Pestalozzistrasse 24, Zurich, 8091, Switzerland

Katja Weiss, Stefania Di Gangi, Markus Inauen, Oliver Senn & Stefan Markun

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K.W., M.I. and S.M. conceived and designed the study. S.D. performed data management and analysis. K.W., S.D. and S.M. drafted the original version of the manuscript. All authors revised the manuscript and approved the final version.

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Weiss, K., Di Gangi, S., Inauen, M. et al. Changes in the attractiveness of medical careers and career determinants during the bachelor’s program at Zurich medical schools. BMC Med Educ 24 , 693 (2024). https://doi.org/10.1186/s12909-024-05693-8

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II Brazilian Society of Rheumatology consensus for lupus nephritis diagnosis and treatment

Edgard Torres dos Reis-Neto ORCID: orcid.org/0000-0003-0657-4825 1 na1 ,
Luciana Parente Costa Seguro ORCID: orcid.org/0000-0003-0538-9476 2 na1 ,
Emília Inoue Sato ORCID: orcid.org/0000-0001-8540-014X 1 ,
Eduardo Ferreira Borba ORCID: orcid.org/0000-0001-6194-5129 2 ,
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Lilian Tereza Lavras Costallat ORCID: orcid.org/0000-0002-3077-9479 4 ,
Marta Maria das Chagas Medeiros ORCID: orcid.org/0000-0002-0389-8421 5 ,
Eloisa Bonfá ORCID: orcid.org/0000-0002-0520-4681 2 ,
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Danielle Christinne Soares do Egypto ORCID: orcid.org/0000-0002-8236-024X 10 ,
Francinne Machado Ribeiro ORCID: orcid.org/0000-0003-0038-983X 3 ,
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Antonio Silaide de Araujo Junior ORCID: orcid.org/0000-0002-9352-9477 1 ,
Cláudia Lopes Santoro Neiva ORCID: orcid.org/0000-0001-7964-990X 12 ,
Debora Cerqueira Calderaro ORCID: orcid.org/0000-0001-5535-3223 9 &
Odirlei Andre Monticielo ORCID: orcid.org/0000-0003-0720-2097 11

Advances in Rheumatology volume 64 , Article number: 48 ( 2024 ) Cite this article

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To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN).

Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion.

All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy.

This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil.

Introduction

Systemic lupus erythematosus (SLE) is a heterogeneous and pleomorphic systemic autoimmune disease characterized by periods of activity and remission with high rates of organ damage and morbimortality [ 1 ]. The incidence of SLE in the city of Natal/Brazil was 8.7 cases per 100,000 inhabitants per year in 2000 [ 2 ], and it is currently estimated that there are 150,000 to 300,000 people with SLE in the country [ 3 ].

Lupus nephritis (LN) occurs in up to 50% of adults with SLE and 80% of juvenile-onset SLE patients, and up to 30% progress to end-stage chronic kidney disease (CKD) in 15 years [ 3 ], with impaired quality of life and socioeconomic impact. Therefore, the early recognition of LN is very important to initiate appropriate treatment that could modify the course of the disease and improve its prognosis.

The last consensus of the Brazilian Society of Rheumatology for LN treatment was published in 2015 [ 4 ]. Since then, specific targets, new treatment options and novel biomarkers to help diagnosis and monitoring SLE have been described. In view of these new available data, associated with the high frequency of SLE in Brazil and the morbimortality of the disease, there is an urgent need to update the Consensus for diagnosis and treatment of LN, which may support decision in clinical practice as well as the development of public and supplementary health policies in Brazil.

This consensus, supported by the Brazilian Society of Rheumatology, was developed by a team of two methodologists and 20 rheumatologists with experience in SLE, members of the SLE Committee of the SBR, who defined 14 PICO questions ( population, intervention, comparator, outcome ) on different aspects of LN treatment (Supplementary Material 1 ). This study was conducted using a systematic review model according to the international recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Eligible randomized controlled trials (RCTs) were included and analyzed: complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease (CKD), renal relapse, and severe adverse events (infections and mortality). The following databases were used for research (supplementary material 2 ): the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (2021, Edition 7), MEDLINE via PubMed (1966 to July 13, 2021), Embase via Elsevier (1974 to July 13, 2021), and Lilacs via the Virtual Health Library (VHL) Regional Portal (1982 to July 13, 2021).

The triage process was performed using Rayyan software. Two authors (ETRN and LPCS) independently selected the titles and abstracts and identified studies that met the eligibility criteria. For the studies included in the first phase, the full texts were retrieved, and eligibility for definitive inclusion was assessed. In cases of discrepancy, a third reviewer (VTC) was consulted. Information regarding the selection stage is described in the PRISMA flowchart (Fig. 1 ). Extraction and management of data were independently performed by two methodologists (VTC and NCJ), who assessed the risk of bias of each included study using version 2 of the Cochrane risk of bias tool version 2 (RoB2) according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, version 6.0.

Literature search flowchart

Tables of the main findings for all outcomes were created. GRADEpro Guideline Development Tool (GDT) software (GRADEpro GDT, McMaster University and Evidence Prime Inc., McMaster University, Hamilton, Ontario, Canada) was used to analyze the overall certainty of the evidence, and each outcome was categorized into four levels of certainty: high, moderate, low, and very low [ 5 ]. The recommendations were prepared according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group guidelines, especially regarding problem priority, balance between benefits and harms, patients’ values and preferences, costs, health equity, acceptability, and feasibility. Seventeen rheumatologists evaluated all the evidence and voted on the recommendations for each PICO question. Recommendations required ≥82% (14/17) agreement among the voting members. The recommendations for each PICO question were classified as follows: strongly in favor, weakly in favor, conditional, weakly against, and strongly against a particular intervention.

Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion.

Diagnoses of lupus nephritis

All patients diagnosed with SLE, even if asymptomatic, should undergo creatinine and urinalysis tests to assess renal involvement. The frequency must be personalized in each case, from 1 to 3 months in the induction therapy to 3 to 6 months in maintenance therapy or asymptomatic patients [ 6 , 7 ]. LN is defined by the presence of persistent proteinuria (>500 mg in 24 h or urinary protein/creatinine ratio (UPCR) > 0.5) and/or active urinary sediment (dysmorphic hematuria or presence of hemoglobin, red blood cells, granular, tubular, or mixed casts) in the absence of infection or another explanation, or by renal biopsy demonstrating immune-mediated glomerulonephritis [ 8 ]. However, lower levels of proteinuria may be present in patients with active proliferative nephritis, which has been called “silent nephritis” [ 9 , 10 ].

According to the analysis of this consensus, 24-h proteinuria and spot UPCR demonstrated a strong correlation [r = 0.82 (0.76–0.83)] (supplementary material 3 ). However, there was high heterogeneity and low agreement between studies, especially when 24-h proteinuria was less than 500 mg or between 500 mg and 1 g [ 11 , 12 , 13 ]. Thus, although spot UPCR is a great test for screening and monitoring patients with LN, we recommend that 24-h proteinuria or 24-h UPCR should be used as the most accurate measure for decisions in clinical practice, including changes in clinical scenarios or in immunosuppressive therapy.

Anti-dsDNA and anti-C1q antibodies are useful for the diagnosis and monitoring of LN activity, especially in proliferative classes. Although the anti-C1q antibody test is not widely available in clinical practice in Brazil, if both are present, the positive predictive value is 67% for LN activity [ 14 , 15 ]. The presence of anti-C1q, anti-dsDNA, and complement consumption increases the risk of LN (OR 14.9; 95% CI 5.8–38.4) [ 16 ]. On the other hand, it is important to reinforce that it is not necessary to treat SLE patients with anti-dsDNA antibodies or complement consumption without clinical disease manifestations [ 17 , 18 ]. Anti-nucleosome antibodies are strongly correlated with anti-dsDNA antibodies and appear earlier in active LN [ 19 ]. The presence of anti-P-ribosomal antibodies seems to be related to class V, conferring a better prognosis, especially in the absence of anti-dsDNA antibodies [ 20 , 21 ]. Anti-neutrophil cytoplasmic antibodies (ANCA), especially the p-ANCA pattern associated with anti-myeloperoxidase (MPO) antibodies, can be detected in LN, particularly in class IV with higher creatinine level and worse prognosis [ 22 , 23 , 24 ].

Kidney biopsy is considered the gold standard for diagnosing LN, establishing histological class (glomerulonephritis classes I to VI), evaluating parameters of activity (graded from 0–24) and chronicity (graded from 1–12) and guiding treatment according to previous published guidelines (Table 1 ) [ 25 , 26 , 27 ]. Tubulointerstitial and vascular involvements should also be analyzed to determine patient prognosis and support differential diagnosis [ 28 ]. It is also useful to identify other pathologies, such as hypertensive or diabetes nephropathy and thrombotic microangiopathy (TMA), which may have implications in treatment decisions and prognosis [ 29 , 30 , 31 ]. Biopsy should be performed when there is suspicion of renal involvement in SLE, including at least one of the following [ 32 , 33 ]:

24-h proteinuria ≥ 500 mg or UPCR ≥ 0.5

Abnormal renal function (increase in serum creatinine >30% or decrease in glomerular filtration rate, GFR) of unknown etiology

Glomerular hematuria with proteinuria <0.5 g/24 h

Differential diagnosis with other conditions, such as hypertension, diabetes mellitus, TMA, podocytopathy, tubulointerstitial lesions, collapsing glomerulopathy, infections, and others.

On the other hand, the delay in starting immunosuppressive treatment (especially in suspected cases of rapidly progressive glomerulonephritis) is associated with worse short- and long-term renal prognoses. Therefore, if kidney biopsy is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters [ 34 ]. Classes I and II represent mesangial involvement that usually manifests with few clinical symptoms and laboratory abnormalities, and there may be mild proteinuria (usually <1 g/24 h) and dysmorphic hematuria. Classes III and IV usually present proteinuria above 500 mg/24 h, dysmorphic hematuria, and/or the presence of red blood cell casts. Hypertension, loss of renal function and rapidly progressive glomerulonephritis can occur in severe cases. Pure class V comprises only 10% to 20% of LNs and usually presents with nephrotic syndrome without leukocyturia or hematuria; also, class V can be associated with class III or IV [III or IV (±V)] [ 35 , 36 ]. A Brazilian study developed an instrument to differentiate classes III or IV (±V) from class V based on clinical and laboratory parameters ( https://ppg.unifesp.br/reumato/comunicados/lupus-nephritis ) [ 36 ], which can help clinical decision if kidney biopsy is not available.

Kidney biopsy should be repeated in cases of refractory disease (persistent proteinuria after one year and/or worsening of serum creatinine) or LN relapse [ 29 , 30 , 31 ].

Practical issues for lupus care: although biopsy remains the gold standard for LN diagnosis, accessibility is limited in Brazil. Therefore, the use of clinical and laboratorial parameters remains the mainstay for diagnosis in most regions of our country. An instrument was recently published in order to differentiate LN classes [ 36 ].

Treatment target: Target Renal Response (TRR)

Assessment of proteinuria is essential in the management of LN since early reduction in proteinuria level is a predictor of renal response. A 1-year proteinuria level <0.7–0.9 g/24 h is the best predictor of long-term renal outcome, assessed by important LN cohorts (Euro-Lupus and MAINTAIN nephritis trials) and by two Brazilian studies including patients with severe disease in real life situation [ 37 , 38 , 39 , 40 , 41 ]. Other predictive parameters of favorable renal outcome are a reduction in proteinuria of 25% at week 8 [ 42 , 43 ], a significant decrease in proteinuria at week 12 [ 39 , 44 ], a reduction ≥50% from baseline at 6 months [ 44 , 45 ], and proteinuria ≤1 g at 6 months of treatment [ 46 ].

Thus, the panelists considered the improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria <0.8 g/24 h at 12 months as the targets of response to treatment; these targets were called the Target Renal Response (TRR) (94.1% agreement). Patients with nephrotic proteinuria at baseline may require an additional 6–12 months to achieve TRR. In these patients, immediate changes to therapy are not necessary if proteinuria improves [ 47 ]. On the other hand, if there is no clinical or laboratory improvement or worsening within 3 months, a change in therapy should be considered.

Practical issues for lupus care: assessment of Target Renal Response (corresponding to a reduction in proteinuria levels at 3 months, 6 months and 12 months after treatment, with preserved renal function compared to baseline), is an easy and effective way to evaluate renal response. The target of proteinuria <0.8 g/day at 12 months was defined according to data from Brazilian patients [ 40 , 41 ] (Fig. 2 ).

Treatment target for lupus nephritis: Target Renal Response (TRR)

Duration of immunosuppressive treatment

Induction immunosuppressive treatment (initial therapy) should last 3 to 6 months and should be followed by maintenance treatment (sequential treatment), lasting at least 3 to 5 years in those who achieve TRR. Immunosuppressive treatment for 4 to 5 years was associated with a lower risk of renal relapse than treatment for 2 to 3 years [ 48 ]. The suspension should be gradual and individualized, and should be carried out under medical supervision, taking into account renal response, number of previous renal relapses, duration of the remission period, presence of renal damage, extrarenal activity, patient preferences and may be guided by biopsy [ 49 ].

There is a discussion on the role of rebiopsy after induction (initial) and/or maintenance (sequential) therapy to identify patients who need to prolong or intensify therapy (patients who persist with histological activity), as well as candidates to discontinue immunosuppressive treatment (patients with complete histological response or activity index ≤2) [ 50 , 51 , 52 ].

Practical issues for lupus care: maintenance (sequential) treatment should last at least 3 to 5 years. Patients with incomplete response, with multiple previous relapses or with renal damage might need longer periods of immunosuppressive treatment.

Definition of refractory lupus nephritis

This topic is a subject of debate and still lacks consensus, given the wide variety of criteria used by different authors [ 53 ]. Refractoriness can be understood as the impossibility of achieving remission of the renal inflammatory process despite appropriate treatment [ 54 , 55 ].

According to this consensus, refractory LN was defined when TRR was not achieved by at least two regimens of induction (initial) therapy or when there were contraindications to other proposed treatments, confirming that there was adherence to treatment.

The persistence of proteinuria and renal dysfunction does not always indicate persistent immune-mediated activity. Proteinuria may result from a lack of adherence to treatment, inadequate control of comorbidities (hypertension, diabetes, infections), drug nephrotoxicity, the presence of other concomitant renal diseases (e.g., TMA, other glomerulopathies), genetic factors (e.g., APOL1 variants, pharmacogenetic resistance to immunosuppressive medications) or LN with a predominance of irreversible lesions (damage). Patients with poor adherence to treatment have more LN relapse and are more susceptible to refractory disease [ 56 ].

Factors associated with worse renal prognosis in LN

Patient characteristics: male sex, juvenile-onset lupus, increased serum creatinine or proteinuria >4 g at diagnosis, frequent relapses, incomplete remission, neuropsychiatric lupus, and thrombocytopenia at diagnosis.

Serological characteristics: positive antiphospholipid antibodies (aPLs) or antiphospholipid syndrome (APS), high-titer anti-dsDNA, anti-C1q, and persistent complement consumption.

Histological features: crescents, TMA or tubulointerstitial damage (interstitial fibrosis, tubular atrophy and interstitial inflammation) [ 33 ].

Treatment of class III or IV lupus nephritis with or without class V [class III or IV (±V)]

Recommendations, as well as their strength and certainty of evidence, are shown in Table 2 and the treatment flowchart is shown in Fig. 3 . For immunosuppressant choice, the following factors should be considered: severity, adherence, availability/access to medication and infusion centers, pregnancy or lactation, risk of infertility, costs, and patient preference (Table 3 ).

Treatment of class III or IV LNs (±V). *Factors to be considered when choosing immunosuppressants: severity, availability, adherence, infusion clinic availability, gastrointestinal tolerance, cumulative dose of CYC, age/fertility, desire for pregnancy. **Target Renal Response (TRR): reduction in proteinuria by 25% at 3 months, 50% at 6 months, and proteinuria < 0.8 g at 1 year associated with maintenance or improvement (±10% baseline) in renal function. Nephrotic proteinuria at baseline may require another 6–12 months to achieve TRR and, in such cases, immediate therapy changes are not necessary if proteinuria is improving. If clinical or laboratory results worse within 3 months, therapy changes should be considered. § Severe Disease, Poor prognostic factors, Impossibility to MMF or CYF Euro-Lupus. ‡ In case of TRR achieved, Mycophenolate + Belimumab or Mycophenolate + Tacrolimus can be used as maintenance therapy for up to 3 years

Question: Should hydroxychloroquine (HCQ) be prescribed to all SLE patients with LN?

Recommendation 1: HCQ should be prescribed to all SLE patients, except if contraindicated. Agreement: 100%.

The use of antimalarial drugs is associated with numerous beneficial effects in SLE patients, including a higher remission rate of LN; a reduction in thrombotic risk; improved lipid and glycemic profiles; lower risks of infection, hospitalization, and progression to metabolic syndrome; better MMF response; damage prevention; and longer survival [ 57 ]. Due to its safety profile, HCQ is preferred over chloroquine diphosphate (CDF).

The recommended dose of HCQ is 5 mg/kg/day of real body weight (maximum dose of 400 mg/day), and for DFQ is 2.3 mg/kg/day (maximum dose of 250 mg/day) [ 58 ]. The dose should be reduced by 50% in patients with GFR < 30 ml/min [ 29 ]. Studies evaluating blood levels of HCQ are useful both for assessing adherence and for monitoring adequate target levels [ 59 , 60 , 61 , 62 ]. Of note, in obese patients (BMI ≥ 30 kg/m 2 ), dose of HCQ should not exceed 5 mg/kg/day of ideal body weight, since it has been demonstrated that even with the recommended maximum daily dose restriction (400 mg/day), these patients have very high HCQ blood levels [ 59 ].

Maculopathy caused by HCQ stands out as one of the most significant adverse events. The major risk factors for retinal toxicity are the use of HCQ and DFQ above the recommended doses, an extended usage exceeding 5 years, impaired renal function, concomitant use of tamoxifen, and previous macular or retinal disease. Ophthalmological evaluation should be performed at the initiation of HCQ therapy and subsequently on annual basis for patients with risk factors for retinal toxicity. Additionally, baseline and after 5 years (annually after this period) for those without risk factors [ 58 ]. More sensitive tests, such as spectral domain-optical coherence tomography (OCT-SD) and automated threshold visual field tests, are recommended for detecting early retinal toxicity [ 63 ].

Practical issues for lupus care: HCQ should be prescribed to all SLE patients, except if contraindicated. More sensitive tests, such as OCT-SD, are recommended for detecting early retinal toxicity. Therefore, avoiding excessive HCQ doses is important to prevent retinal toxicity. Obese patients (BMI ≥ 30 kg/m 2 ) should use 5 mg/kg/day of ideal body weight (maximum 400 mg/day), as suggested by a recent Brazilian study [ 59 ].

Question: How should glucocorticoids be used in induction and maintenance therapy?

Recommendation 2: Glucocorticoids should be used at the lowest dose and for the minimal necessary period. Agreement: 100%.

Glucocorticoids (GC) exert rapid effect on the inflammatory process, with immediate benefits in controlling disease activity [ 64 ]. However, they are associated with several adverse events and damage accrual [ 65 ]. GC are related to 58% of first year damage and 80% of late damage (after 15 years of disease) [ 65 , 66 ]. Some protocols using lower doses of GC have shown similar efficacy with less adverse events [ 67 , 68 ]. GC are recommended for induction (initial) treatment, using the lowest dose, for the minimal necessary period and associated with immunosuppressants.

The consensus suggests that intravenous (IV) pulse therapy with methylprednisolone should be given at a preferred dose of 500 mg/day (ranging from 250 to 750 mg/day) for 1–3 days, followed by oral prednisone 0.5 mg/kg/day (ranging from 0.25 to 0.7 mg/kg/day), with progressive dose reduction and a target of ≤5 mg/day in 3 to 6 months.

Practical issues for lupus care: Similarly to other international recommendations, this consensus strongly recommends that glucocorticoids should be used at the lowest dose and for the minimal necessary period, in order to prevent damage accrual.

Induction therapy

Question: is there a preference for mycophenolate mofetil (mmf) or cyclophosphamide (cyc) as induction therapy for ln.

Recommendation 3: Induction therapy should involve the use of either MMF or intravenous CYC. Strength of recommendation: conditional. Certainty of evidence: moderate. Agreement: 94.1%.

In class III or IV LN (±V), induction treatment includes either MMF (2 to 3 g/day) or intravenous CYC at a dose of 500 mg every 2 weeks for 3 months [EuroLupus Nephritis Trial protocol (Euro-Lupus)]. National Institutes of Health (NIH) CYC protocol, with monthly doses of 0.5–1.0 g/m 2 of body surface area for 6 months, involves higher CYC cumulative dose. The pooled analysis of data from RCTs comparing these strategies showed, with moderate certainty of evidence, similar complete and partial remission rates between the groups at the 24-week evaluation. There was also no significant difference between the groups in terms of serum creatinine or proteinuria, although there was certainly weak evidence for these outcomes. Likewise, there was no significant difference between treatments regarding important adverse events such as infections and mortality [ 44 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ]. In the Aspreva Trial, MMF and CYC had similar efficacy overall to short-term induction therapy for LN and more Black and Hispanic patients responded to MMF than IVC. However, as these factors are inter-related, it is difficult to draw firm conclusions about their importance [ 78 ]. In cases of gastrointestinal intolerance to MMF, mycophenolate sodium (MFS) may be administered at a dosage of 1.44 to 2.16 g/day [ 79 ].

The choice of medication should consider factors such as patient age, desire for pregnancy, risk of infertility or early menopause, previous cumulative dose of CYC, availability of an infusion center, patient adherence to medications, previous gastrointestinal intolerance to MMF/MFS, and clinical and histological parameters of severity. In patients of childbearing age, the risk of infertility associated with CYC must be clearly shared with the patient, particularly when administered at high doses.

The Euro-Lupus protocol presents a lower cumulative CYC dose, and it has similar efficacy to that of the NIH regimen after a 10-year follow-up period [ 44 , 77 ], including in patients outside European continent [ 70 ]. Euro-Lupus CYC Pivotal studies excluded patients with crescentic glomerulonephritis or a GFR < 25–30 mL/min [ 70 , 71 , 72 , 74 , 75 , 76 , 77 ]. Post hoc analysis of the ASPREVA Lupus Management Study revealed no difference in response to treatment with MMF or the CYC NIH in patients with a GFR < 30 mL/min. However, there were few patients in each group, and the pivotal study was not designed for this purpose [ 80 ]. Therefore, considering the efficacy data and the increased risk of infertility and early menopause with higher doses of CYC, the CYC NIH regimen should be reserved for patients with poor prognostic factors, such as GFR < 30 mL/min or kidney biopsy with cellular crescents, fibrinoid necrosis, or severe tubulointerstitial nephritis in ≥50% of glomeruli, as well as for patients treated in centers with structural limitations to provide infusions or clinical visits more frequently (every 2 weeks).

Practical issues for lupus care : either MMF or CYC can be used as first line immunosuppressive drugs for induction LN therapy. MMF was recently incorporated into the treatment of LN by the Public Health System in Brazil, which simplifies patients’ access to medication. IV CYC is preferred for non-adherent patients to oral medication although it requires an infusion center. CYC NIH should be reserved for patients with more severe forms of LN due to higher CYC cumulative doses and adverse events, including infertility.

Question: Can the combination of MMF and tacrolimus (TAC) be used as induction therapy for LN?

Recommendation 4: The combination of MMF and TAC can be used in induction therapy, particularly if there is a lack of response or impossibility to use CYC or higher doses of MMF (induction dose). Strength of recommendation: weakly in favor. Certainty of Evidence: moderate. Agreement: 82.3%.

TAC is a calcineurin inhibitor with immunosuppressive effects similar to those of cyclosporine (CsA). Its mechanism of action involves both T cells immunosuppression and direct antiproteinuric effect due to podocyte cytoskeleton stabilization and reduction of glomerular perfusion pressure through afferent arteriolar constriction [ 81 ]. While CsA is associated with a greater risk of dyslipidemia, hypertension, gingival hyperplasia, hypertrichosis and hyperuricemia, TAC is associated with a greater frequency of diabetes and alopecia. Nephrotoxicity can occur with these medications, both acute (TMA, afferent arteriolar vasoconstriction, tubular dysfunction, fluid and electrolyte disturbances) and chronic (glomerular sclerosis, arteriolar thickening, tubular atrophy or interstitial fibrosis) [ 82 ].

Studies limited to Asian population, with two RCTs including 402 patients evaluated LN induction therapy with 1000 mg of MMF combined with 4 mg of TAC (divided in two doses) versus CYC NIH. The group with multitarget therapy (MMF + TAC) presented a 33.4% greater rate of CRR (relative risk (RR) 2.37; CI 1.07–5.26; moderate certainty of evidence), with no difference in creatinine levels at 6 months or in the incidence of infections or mortality, compared to CYC. However, these studies excluded patients with creatinine >3 mg/dL; there is a lack of data on long-term histological renal outcomes; and more studies are needed to determine the efficacy and safety of MMF + TAC therapy in other populations [ 83 , 84 , 85 ].

TAC for LN is not recommended for patients with creatinine >3 mg/dL, should be avoided for patients with TMA on kidney biopsy, and requires the monitoring of creatinine, blood pressure (BP), and blood glucose after initiation [ 81 , 82 , 83 , 84 , 85 ]. Although there are only a few studies, the association of MMF and CsA can be evaluated when TAC is contraindicated or unavailable [ 86 , 87 ].

Practical issues for lupus care: This consensus also suggests MMF plus TAC as induction therapy, particularly if there is lack of response or impossibility to use CYC or higher doses of MMF (induction dose). However, the limited accessibility of TAC in most regions of Brazil and the scarcity of evidence among non-Asian patients should be emphasized. TAC is not recommended in patients with TMA and/or creatinine >3 mg/dL.

Question: When belimumab (BEL) combined with standard of care therapy can be indicated for LN patients?

Recommendation 5: The combination of BEL and MMF can be used as induction therapy according to specific characteristics of patient. Strength of recommendation: conditional. Certainty of evidence: moderate. Agreement: 94.1%.

A double-blind, randomized, placebo-controlled study evaluated the use of BEL (10 mg/kg intravenously) at 0, 2, and 4 weeks and then every 4 weeks combined with standard therapy (MMF or CYC Euro-Lupus followed by AZA) and reported an 11% increase in renal response rates (PERR—primary efficacy renal response: uPCR ≤ 0.7; GFR ≥ 60 mL/min/1.73 m 2 or no more than 20% worse than the preflare value; no need for rescue therapy) at 2 years in those who responded to treatment (NNT = 9) and a 10.3% increase in CRR (RR 1.51; CI 1.09–2.12; moderate certainty of evidence), with no difference in the incidence of infections [ 88 ]. Post hoc analysis of the pivotal study suggested a better response in subgroups with histological class III or IV, in those with baseline proteinuria < 3 g/g, and in combination with MMF as an immunosuppressant, with twice the chance of achieving CRR as those in combination with CYC Euro-Lupus, which was probably underrepresented in the study compared to MMF. Finally, treatment with BEL combined with standard therapy reduced the chance of new renal flares by 11.6% ( p = 0.0008) [ 89 ].

Thus, BEL must be used in combination with standard therapy (CYC Euro-Lupus or MMF) for LN. Given current studies, BEL can be combined preferably with MMF in patients with class III or IV renal biopsy and proteinuria < 3 g/24 h at baseline. In addition, it should be considered in patients with difficulty in reducing GC dose, high risk of progression to damage, associated extrarenal manifestations, high risk of relapse or frequent relapses, and a high risk of progression to CKD. It should not be recommended to treat LN for those on renal replacement therapy or with a GFR < 30 mL/min, except in cases of extrarenal manifestations [ 88 , 89 , 90 , 91 ]. The subcutaneous presentation can also be administered at a dose of 400 mg weekly in the first month followed by a dose of 200 mg weekly thereafter.

Practical issues for lupus care: BEL can be combined preferably with MMF to enhance renal response, decrease the risk of new flares and help to reduce oral GC dose. It should be considered in patients with difficulty in reducing GC dose, high risk of progression to damage, associated extrarenal manifestations, high risk of relapse or frequent relapses, and high risk of progression to CKD.

Question: Can TAC be used as immunosuppressant in monotherapy in induction therapy in patients with LN?

Recommendation 6: TAC as an immunosuppressant in monotherapy can be used as induction therapy if MMF, CYC, MMF + TAC or BEL + MMF cannot be used. Strength of recommendation: conditional. Certainty of evidence: moderate. Agreement: 100%.

Research conducted exclusively on Asian population suggest that TAC exhibit comparable efficacy to CYC and MMF in LN induction treatment. The dose used ranged from 0.05 to 0.1 mg/kg/day, divided into two daily doses. Tacrolinemia is monitored, with a target of 4 to 8 ng/mL, 6 to 8 ng/mL, or 5 to 10 ng/mL, depending on the study. Patients with severe renal impairment and crescentic glomerulonephritis were excluded from the studies [ 72 , 92 , 93 , 94 , 95 ]. Compared to that of CYC NIH, TAC is noninferior during induction treatment of LN [ 93 ]. A 2-year multicenter RCT revealed a similar response rate and increased risk of leukopenia and gastrointestinal symptoms in the CYC NIH group [ 92 ]. A small prospective RCT evaluated 60 patients with active LN treated with CYC, MMF, or TAC and reported similar complete renal response (CRR) (30%, 45% and 40%, respectively; p > 0.05) and partial renal response (PRR) (60%, 75% and 70%, respectively; p > 0.05) with rapid improvement in proteinuria and an increase in serum albumin in the TAC group [ 72 ]. According to the analysis of the RCTs included in the consensus, there was a better rate of CRR (RR 1.38; 1.09–1.75) for TAC than for CYC, with a moderate certainty of evidence. MMF and TAC had similar CRRs (RR 0.91; 0.65–1.27). Additional studies involving diverse populations is warranted.

Practical issues for lupus care: This consensus suggests that TAC monotherapy can be considered as induction therapy if MMF, CYC, MMF + TAC or BEL + MMF cannot be used. TAC accessibility is limited in most regions of Brazil.

Question: Can voclosporin be used as an induction treatment for LN?

Recommendation 7: The combination of MMF and voclosporin may be considered for induction therapy after its approval by Brazilian regulatory agencies. Strength of recommendation: weakly in favor. Certainty of evidence: low. Agreement: 94.1%.

Voclosporin is a calcineurin inhibitor that is analogous to CsA but has better metabolic stability and a similar mechanism of action, blocking proliferation and responses mediated by T lymphocytes and stabilizing renal podocytes [ 81 , 96 , 97 ].

Phase II (AURA-LV) [ 96 ] and a phase III (AURORA 1) [ 97 ] studies reached their primary endpoints. AURORA 1 evaluated voclosporin 23.7 mg + mycophenolate 1 g twice daily with low-dose corticosteroids in LN patients with class III and IV with UPCR ≥ 1.5 g/g or class V UPCR ≥ 2 g/g and found a greater chance of achieving the primary endpoint at 52 weeks (41% versus 23%/OR 2.65; 95% CI 1.64–4.27; p < 0.0001) (97). Voclosporin was approved for the LN treatment in the USA in 2021. In Brazil, voclosporin has not been approved by regulatory agencies yet, and the posology for this combination (10 pills/day) raises concerns regarding adherence.

Practical issues for lupus care: Although studies demonstrated the effectiveness of voclosporin plus MMF as induction therapy for LN, the former drug is not approved in Brazil.

Question: Can CsA be used as an induction therapy in LN?

Recommendation 8: CsA as an immunosuppressant in monotherapy is not recommended for induction therapy. Strength of recommendation: strongly against. Certainty evidence: very low. Agreement: 82.3%.

CYCLOFA-LUNE, an open, multicenter RCT, evaluated the use of CYC or CsA for the induction and maintenance therapy of LN proliferative with preserved renal function and reported similar results between the two drugs, considering response and adverse effects [ 98 ]. Due to the limited number of RCTs and the associated risk of drug toxicity, especially in chronic use, panelists do not recommend CsA as immunosuppressant in monotherapy for Class III or IV (± V) LN.

Practical issues for lupus care: Due to the limited number of studies, this consensus does not recommend CsA monotherapy for proliferative LN induction therapy. Caution with arterial hypertension, hyperglycemia, hypertrichosis and worsening renal function is important when using CsA.

Question: Can leflunomide (LFN) be used as an induction therapy for LN?

Recommendation 9: LFN as immunosuppressant in monotherapy is not recommended for induction therapy. Strength of recommendation: strongly against. Certainty of evidence: very low. Agreement: 88.9%.

LFN, an inhibitor of dihydroorotate dehydrogenase, has antiproliferative and anti-inflammatory effects by decreasing T cells and B cells. Despite the low quality of available evidence, some observational studies and one small RCT suggested that LFN is safe and well tolerated and may be an effective induction treatment for proliferative LN. These studies predominantly involved Asian SLE patients [ 99 , 100 , 101 , 102 ].

A recent RCT study in Chinese patients evaluated LFN 40 mg/day for 3 days followed by 20 mg/day versus CYC 0.8–1.0 g monthly as an induction treatment for proliferative LN and reported similar efficacy and safety profiles. The study included fewer patients than the original sample size calculated, and the follow-up only lasted 24 weeks [ 103 ]. A systematic review encompassing 254 patients evaluated the efficacy and safety of LFN compared to CYC in Chinese adults with LN and, despite the small sample and high heterogeneity of the studies, suggested a similar favorable safety profile of LFN in these patients [ 104 ].

Given the overall low quality of the evidence regarding the use of LFN for proliferative LN induction therapy, coupled with the predominantly Asian population and limited follow-up duration in the available studies, the panel strongly advises against the use of LFN for proliferative LN induction therapy.

Practical issues for lupus care: Due to the limited number of studies and quality of evidence, this consensus does not recommend LFN monotherapy for LN induction therapy.

Question: Should pulse therapy with methylprednisolone be combined with CYC throughout induction therapy for LN?

Recommendation 10: Monthly glucocorticoid pulse therapy is not recommended during induction therapy. Strength of recommendation: strongly against. Certainty of evidence: very low. Agreement: 88.2%.

Since the discovery and application of GC in the 1950s, this class of medication has been very important in the treatment of various immune-mediated rheumatic diseases [ 105 ]. It has been used as an anchor medication for many years and is combined with standard therapy. On the other hand, it presents a risk of serious adverse events and damage [ 65 ].

A randomized study evaluated the effect of combined therapy with CYC NIH and pulse therapy with monthly methylprednisolone (1 g/m 2 body surface area) versus each therapy alone. There was no difference between combined therapy and CYC alone, with a possibly greater risk of adverse events [ 106 , 107 ]. Thus, pulse therapy with methylprednisolone combined with CYC or other immunosuppressants throughout the induction treatment is not recommended.

Practical issues for lupus care: monthly GC pulse therapy is not recommended, in order to avoid damage accrual.

Maintenance therapy

Question: can mmf or aza be used as maintenance therapy for ln.

Recommendation 11: Both MMF or AZA can be used as maintenance therapy. Strength of recommendation: conditional. Certainty evidence: very low. Agreement: 82.3%.

MMF and AZA are the most indicated medications for LN maintenance treatment [ 29 ]. The MAINTAIN study included 105 European patients who received AZA 2 mg/kg/day or MMF 2 g/day after induction treatment with CYC Euro-Lupus [ 108 ], and long-term analyses confirmed the lack of superiority of any of the strategies regarding renal activity and progression to CKD [ 39 ]. The multicenter ALMS study evaluated 227 patients who received AZA or MMF after induction therapy with CYC or MMF and revealed the superiority of MMF in terms of renal relapse, progression to CKD, and the need for rescue therapy. Importantly, ALMS multiethnic cohort, including Europeans, Asian, Hispanic, and African American populations, demonstrated the superiority of MMF in these populations [ 109 ]. Regarding adverse events, there was no difference between the number of infections or malignancies, and those using AZA had more hematological adverse events [ 110 ].

We recommend the use of MMF 1–2 g/day or AZA 2 mg/kg/day for LN maintenance treatment. The choice of strategy should consider patient individual characteristics. For those who receive induction treatment with MMF, it is recommended to maintain the same drug during maintenance treatment according to data from the ALMS study which showed that these patients have a worse response when switching to AZA. However, AZA should be used as maintenance therapy in pregnancy and for those planning pregnancies as well as those intolerants to MMF [ 29 , 109 ]. The availability, cost and dosage regimen (frequency) of the medication should also be taken into consideration [ 29 , 31 ].

Practical issues for lupus care: both MMF or AZA can be used as maintenance therapy. For those who receive induction treatment with MMF, it is recommended to maintain the same drug during maintenance treatment. AZA can be used during pregnancy and pregnancy planning, and has a better posology than MMF, with fewer pills a day and less gastrointestinal intolerance.

Question: Can calcineurin inhibitors (CsA or TAC) be used as maintenance therapy for LN?

Recommendation 12: Calcineurin inhibitors (TAC or CsA) can be used as maintenance therapy in patients who cannot use MMF or AZA. Strength of recommendation: weak against. Certainty evidence: very low. Agreement: 94.1% for CsA and 100% for TAC.

Few quality RCTs have evaluated the outcomes of these drugs in maintenance therapy, so they are not recommended as first-line therapy. A study in a China compared the efficacy of TAC (with a serum concentration of 4 to 6 ng/mL) with that of AZA (2 mg/kg/day) as maintenance therapy for only 6 months and revealed no differences in CRR, PRR or adverse events [ 111 ]. An Italian multicenter, randomized, controlled study compared the efficacy of CsA and AZA in LN maintenance treatment after induction therapy with oral CYC for 3 months. Proteinuria reduction occurred in both groups but was more rapidly with CsA. However, the small number of patients and of renal flares in both groups precluded definite conclusions [ 112 ].

Practical issues for lupus care: Calcineurin inhibitors (TAC or CsA) can be used as maintenance therapy in patients who cannot use MMF or AZA. Awareness of calcineurin inhibitors renal acute and chronic toxicity is necessary.

Question: Can LFN be used as maintenance therapy for LN?

Recommendation 13: LFN can be used as maintenance therapy in patients who cannot use MMF or AZA. Strength of recommendation: weak against. Certainty of evidence: very low. Agreement: 94.1%.

Only one open-label, noninferiority RCT, evaluated LFN and AZA for 36 months maintenance therapy in Chinese patients with proliferative LN, who achieved complete renal response after monthly induction therapy with monthly CYC for 6–9 months. LFN was found to be noninferior to AZA in terms of efficacy and safety [ 113 ]. The lack of evidence regarding LFN efficacy in proliferative LN maintenance therapy, coupled with the limited data form a single study involving solely Asian patients, precluded the panel from endorsing LFN as first-line therapy in this scenario. However, in patients who do not respond to MMF or AZA or who present considerable toxicity, LFN may be considered a therapeutic option.

Practical issues for lupus care: LEF can be considered for maintenance therapy in patients who cannot use MMF or AZA.

Question: Should CYC be used in maintenance therapy for LN?

Recommendation 14: CYC is not recommended for maintenance therapy. Strength of recommendation: strongly against. Certainty of evidence: very low. Agreement: 94.1%.

Only one open-label RCT after LN induction treatment compared CYC (0.5 to 1.0 g/m 2 every three months), AZA (1 to 3 g/kg per day), and MMF (0.5 to 3 g/day) for 1 to 3 years as maintenance therapy in a Chinese patient. The composite outcome of patient and renal survival was greater in the AZA ( p = 0.009) and MMF ( p = 0.05) groups. LN recurrence was less frequent among those using AZA ( p = 0.02), with a greater frequency of hospitalizations, amenorrhea and infections with CYC [ 114 ]. The CYCLOFA-LUNE, an open, multicenter RCT, evaluated the efficacy of CYC versus CsA for both induction and maintenance of proliferative LN with preserved renal function. The study revealed comparable treatment response rates and adverse effects with both drugs [ 98 ].

Although CYC has historically been used as LN maintenance therapy, its adverse effects, especially those related to prolonged exposure time and cumulative dose, prompts caution. With the availability of newer, more effective therapeutic options with a lower risk profile of adverse events, CYC should not be recommended as maintenance therapy.

Practical issues for lupus care: CYC is not recommended for maintenance therapy due to adverse events related to CYC prolonged exposure and cumulative dose.

Treatment of class V LN

Pure class V comprises approximately 10 to 20% of LN patients and, for this reason, is underrepresented in most RCTs [ 115 ]. Up to 30% of patients may progress to CKD within 10 years [ 115 , 116 ] and treatment involves the use of corticosteroids and immunosuppressants [ 95 , 117 , 118 , 119 ] (Fig. 4 ).

Treatment of class V LN. *Factors to be considered when choosing immunosuppressants: severity (proteinuria and serum albumin levels), availability, adherence, infusion clinic availability, gastrointestinal tolerance, CYC cumulative dose, age/fertility, desire for pregnancy. **Target Renal Response (TRR): reduction in proteinuria by 25% at 3 months, 50% at 6 months, and proteinuria < 0.8 g at 1 year associated with maintenance or improvement (±10% baseline) in renal function. Nephrotic proteinuria at baseline may require another 6–12 months to achieve TRR and in such cases, immediate therapy changes are not necessary if proteinuria is improving. If clinical or laboratory worse within 3 months, therapy changes should be considered. § Severe Disease, Poor prognostic factors, Impossibility to MMF or CYF Euro-Lupu

Pulse therapy with IV methylprednisolone should be performed at a dosage of up to 500 mg/day for 1–3 days, followed by oral prednisone 0.25 to 0.5 mg/kg/day, with progressive reduction of the dose and a target dose of ≤5 mg/day in 3 to 6 months.

The following immunosuppressants can be used to treat class V LN: MMF, CYC, AZA, combination of MMF and calcineurin inhibitor (TAC or CsA), calcineurin inhibitor (TAC or CsA). The choice of the immunosuppressant should take into consideration: severity (proteinuria and serum albumin levels), patient adherence, availability/access to medication and infusion centers, pregnancy or lactation, risk of infertility, costs, and patient opinion (Table 3 ).

Nephroprotective measures are extremely important in the management of class V LN. Blood pressure control and use of antiproteinuric drugs are essential to control proteinuria [ 120 ]. It is also important to stop smoking, avoid the use of nephrotoxic drugs and have a low salt diet. Nephrotic proteinuria is associated with dyslipidemia and increased thrombotic risk and preventive treatment is indicated. These measures are described below in session 11 (adjunctive measures beyond immunosuppression).

Practical issues for lupus care: this consensus recommends the use of GC and immunosuppressants for the treatment of pure class V LN. Nephroprotective measures, blood pressure control and use of antiproteinuric drugs are essential to control proteinuria in pure class V LN.

Refractory LN

Rituximab (RTX) is an IgG1 anti-CD20 monoclonal antibody that induces B lymphocyte depletion. LUNAR pivotal study evaluated RTX as an add-on therapy (associated with MMF) and found no differences in CRR (normal serum creatinine or <115% of baseline; normal urinary sediment and UPCR < 0.5) and PRR (creatinine <115% of baseline; urine 1 < 50% erythrocytes of baseline and absence of erythrocyte casts and 50% decrease in UPCR, with 24 h proteinuria < 1 g or <3 g if nephrotic) between the groups RTX+MMF and Placebo+MMF [ 121 ].

Data from observational studies, open-label trials and systematic reviews [ 122 , 123 ] support the use of RTX in LN, with beneficial effects and evidence of renal response, especially in refractory patients. Therefore, we recommend RTX for the treatment of refractory Class III, IV or V LN.

Practical issues for lupus care: this consensus recommends RTX for refractory LN (Chart 1 ).

Adjunctive measures beyond immunosuppression

Adjunctive measures beyond immunosuppression in LN patients

Patient education

Patient participation in the shared decision-making process, including diagnosis, follow up and treatment, can significantly contribute to treatment success. In addition to immunosuppressive treatment, patient must understand the importance of nephroprotective measures and of adhering to their treatment [ 29 , 120 , 124 ]. It is also relevant to raise awareness about photoprotection and smoking cessation, as they are associated with SLE flares [ 125 ].

Blood pressure (BP) target in patients with LN

BP should be controlled at levels ≤120/80 mmHg (degree of agreement 92.3%) with careful consideration for patient tolerance to medications. Recently, KDIGO suggested that, for adult patients with hypertension or non-dialytic CKD, the target of systolic blood pressure should be <120 mmHg. In case of transplant patients, the target was considered <130/80 mmHg [ 33 ].

Nonpharmacological measures should include a low-sodium intake diet, moderate-intensity physical activity for at least 150 min per week or at a level compatible with physical and cardiovascular tolerance, maintenance of ideal weight, avoidance of alcohol abuse, and adoption of a cardioprotective diet [ 33 , 126 ].

Antiproteinuric drugs

Inhibitors of the renin–angiotensin system (angiotensin-converting enzyme inhibitors [ACEis] or angiotensin receptor blockers [ARBs]) are recommended as first-line therapies for the treatment of patients with hypertension and/or for those with proteinuria even without hypertension, due to antiproteinuric, antihypertensive and nephroprotective effects. These treatments should be discontinued if renal function continues to deteriorate (>30%) and/or if refractory hyperkalemia occurs. The combination of ACEIs and ARBs (double blockade) should not be routinely recommended [ 33 , 126 ]. To attain the BP target and make medication dose adjustments, home monitoring of BP is recommended.

Inhibitors of sodium–glucose cotransporter 2 (SGLT2) appear to be promising antiproteinuric agents for treating LN and may be useful in patients with CKD (GFR > 25 ml/min) whose proteinuria persists despite immunosuppressive treatment. Data on LN are limited, but there are studies on heart failure and diabetic and nondiabetic nephropathy demonstrating important nephroprotective and cardioprotective effects [ 127 , 128 , 129 ].

Dyslipidemia treatment in patients with LN

SLE should be considered an independent risk factor for atherosclerotic disease [ 130 , 131 , 132 ]. Since LN patients are at moderate risk, the LDL target is <100 mg/dL according to the recommendations of the European Society of Cardiology. Patients with CKD (defined by GFR and/or proteinuria), and those with documented atherosclerotic cardiovascular disease (clinically or unequivocal on imaging) should be classified as either at high or very high risk. In such cases, the LDL targets are <70 mg/dl or <55 mg/dL, respectively (associated with ≥50% LDL reduction from baseline) [ 133 ].

Prevention of glucocorticoid-induced osteoporosis (GIO)

SLE patients have a greater risk of osteoporosis. GC use is the main risk factor for bone loss. In addition, the incidence of fractures varies from 30% to 50% among those taking glucocorticoids for more than three months [ 134 ]. Patients should be encouraged to address or discontinue associated modifiable risk factors, such as smoking, alcohol consumption, and physical inactivity/sedentarism [ 134 , 135 ]. GC prescription should be at lowest effective dose and for the shortest possible duration. Bone densitometry and radiography of the thoracic and lumbar spine are important for evaluating the severity of bone mass reduction and the risk or presence of fracture [ 135 ].

A diet rich in calcium (1 g/day) or supplemented in cases of an insufficient diet, associated with the maintenance of adequate serum vitamin D levels (>30 ng/mL) is important for bone mineralization and prevention of GIO [ 134 , 135 ].

The indication for specific drug treatment takes into account age, fracture risk, glucocorticoid dose and gestational desire [ 134 ]. Patients at very high risk (use of prednisone or equivalent ≥30 mg/day for >30 days; prior OP fracture; or BMD T-score ≤ −3.5) and patients > 40 years at high risk should be treated (densitometric osteoporosis or high risk FRAX). Treatment can be considered in patients with moderate FRAX risk. Assessment tool for Brazilian population (>40 years) is available at https://abrasso.org.br/calculadora/calculadora/ . FRAX should be adjusted for glucocorticoid dose (when GC dose is >7.5 mg/day, the risk for major fractures is multiplied by 1.15; and for hip fractures is multiplied by 1.2) [ 135 ].

The drugs available for the treatment of osteoporosis in Brazil are bisphosphonates, denosumab, teriparatide and romosozumab. Premenopausal women should preferably be treated with oral bisphosphonates. Zoledronate and alendronate are contraindicated when the GFR is <35 mL/min, and risedronate and ibandronate are contraindicated when the GFR is <30 mL/min [ 135 ].

Antiphospholipid antibodies and prevention of thromboembolism

The presence of antiphospholipid antibodies (aPLs) including lupus anticoagulant, anticardiolipin IgG and IgM and anti-beta-2-glycoprotein I IgG and IgM should be investigated in all SLE patients. Approximately 30–50% of SLE patients are aPL positive, and about 15% to 30% will develop antiphospholipid syndrome (APS) [ 136 , 137 ]. Prophylactic treatment with low dose aspirin (75–100 mg/day) is recommended in SLE patients with a high-risk aPL profile, and may be considered in those patients with a low-risk aPL profile. In the case of APS, treatment should follow specific guidelines according to clinical phenotype [ 138 ].

Nephrotic proteinuria, especially membranous glomerulonephritis with hypoalbuminemia (<20 g/dL), is associated with a greater risk of thromboembolic events, especially in the first 6 months after the diagnosis. Despite the absence of RCTs, some authors have suggested a benefit of thromboembolic event prophylaxis in these patients [ 29 ]. The serum albumin concentration is a strong predictor of thromboembolic events. KDIGO recommends prophylaxis for thrombosis in patients with an albumin concentration < 2.5 g/dL and associated risk factors (proteinuria > 10 g/day, BMI > 35 kg/m 2 , hereditary thrombophilia, aPL, class III or IV heart failure, recent orthopedic or abdominal surgery, prolonged immobilization, pregnancy, malignancy, previous thromboembolic event, GC use) [ 33 ]. Lin et al. suggests prophylaxis in patients with an albumin concentration <3.0 g/dL and associated risk factors [ 139 ]. The treatments of choice are heparin or vitamin K antagonists, and prophylactic treatment should be continued until there is a significant improvement in proteinuria levels and serum albumin reaches the level of 3.0 g/dL [ 33 ]. The risk of bleeding should be assessed before prescribing thrombotic prophylaxis.

Immunization and infection prevention

SLE patients have a greater risk of infection, which is an important cause of morbidity and mortality [ 140 , 141 ]. Thus, early and appropriate prevention, detection and treatment are essential in infection management of immunosuppressed patients.

Screening for hepatitis A, hepatitis B, hepatitis C, HIV, and syphilis is recommended before starting immunosuppressive therapy. Prophylactic treatment should be considered in patients with a history of cured hepatitis B (anti-HBc+/anti-HBs+) who in planning B-cell-depleting therapy or intense immunosuppression. In patients with active hepatitis C, antiviral therapy should be considered [ 140 , 142 ]. The prevention of Strongyloides stercorallis hyper infection syndrome with the use of antiparasitic drugs is recommended for patients receiving high doses of glucocorticoids, especially in pulse therapy regimens. Ivermectin (200 µg/kg/day for 2 days, repeated after 2 weeks) is an option with good efficacy and safety profile [ 143 ].

SLE patients also have a greater risk of developing tuberculosis than general population. Screening for latent tuberculosis should follow the recommendations of health regulatory agencies in Brazil. Treatment of latent tuberculosis is recommended for patients with a positive epidemiology and/or positive screening test (PPD ≥ 5 mm or IGRA+) and/or radiographic findings suggestive of previous contact with tuberculosis [ 4 , 142 ].

Pneumocystis jiroveci pneumonia (PJP) is an opportunistic lung infection with high morbidity. It can affect immunosuppressed patients and can be prevented with antibiotic prophylaxis. Although some studies have shown a low incidence of PJP in SLE patients (0.04% to 5%), these patients have a high mortality rate (up to 60%). There are still no specific recommendations for prophylactic therapy for SLE, and this topic remains controversial. The use of prednisone >7.5 mg/day, CYC, MMF, rituximab, interstitial pneumonia and LN are risk factors for PJP, while the use of HCQ seems to be a protective factor. Prophylaxis may be considered for patients with a history of PJP and/or risk factors and/or with persistent lymphopenia (<500/mm 3 ) [ 142 , 144 , 145 , 146 ].

Regarding Covid-19 infection, SLE patients may have a high risk of complications, especially when using RTX or high-dose GC. Preventive measures and vaccination against COVID-19 should be recommended for SLE patients, and the use of antivirals should be considered for high-risk infected patients [ 147 , 148 ] according to recommendations of the Brazilian regulatory agencies.

HPV infection is a risk factor for cervical cancer in SLE patients [ 149 ]. Periodic evaluation with oncotic colpo cytology is essential, and vaccination against HPV should be also recommended according to specific guidelines [ 150 ].

One of the most effective measures for the prophylaxis of infections is vaccination. Although efficacy may be reduced in SLE patients, most of them develop protective levels of antibodies after vaccination, with a low risk of disease reactivation [ 142 , 151 ]. Vaccines should be administered, preferably 2 to 4 weeks before the beginning of immunosuppressive/immunobiological therapy or in the period of clinical remission, but vaccine indication should not delay the treatment, especially in severe cases and in those at risk of rapid damage progression. Vaccination against influenza, COVID-19, pneumococcus, meningococcus, Haemophilus influenzae B, tetanus, diphtheria, pertussis, hepatitis A and B, HPV, and recombinant herpes zoster is recommended. Vaccines with live attenuated microorganisms are generally contraindicated in immunosuppressed patients. Exceptions include the risk of yellow fever during epidemic situations or for those travelling for endemic areas. In such cases, a shared decision should be discussed with the patients, considering evidence that the vaccine is safe for those with low immunosuppression [ 152 , 153 ].

Prophylaxis with hyperimmune immunoglobulin is indicated after contact with measles and varicella-zoster immune globulin (VZIG) after contact with chickenpox in the contagious phase. [ 140 , 142 ].

Special situations

Lupus podocytopathy.

Lupus podocytopathy is a rare renal manifestation occurring in 1 to 2% of SLE patients and is not included in the classification of LN [ 25 , 26 ]. Clinically, it presents as nephrotic syndrome resembling class V LN, but light microscopy of the kidney biopsy reveals one of three patterns: normal glomeruli (minimal change type), mesangial glomerulonephritis or focal segmental glomerulosclerosis (FSGS). Thus, podocytopathy should be suspected in patients with nephrotic proteinuria and class I or II LN or FSGS on light microscopy. On immunofluorescence, deposits of immune complexes are absent or restricted to the mesangium (absence of subepithelial or subendothelial immune deposits). The finding of diffuse podocyte effacement (usually greater than 70%) on electron microscopy confirms the diagnosis [ 154 , 155 , 156 ].

Treatment is based on observational and retrospective studies and includes the use of glucocorticoids and immunosuppressants (MMF, CsA, TAC, CYC and RTX). In patients with extensive and severe podocyte effacement, calcineurin inhibitors appear to be associated with a higher rate of remission and may be used as first-line therapy [ 154 ].

Involvement of the vascular compartment

Vascular findings secondary to SLE on kidney biopsy include TMA, lupus vasculopathy (with noninflammatory necrotizing lesions with variable immune deposits), and lupus vasculitis (necrotizing and inflammatory vasculitis with infiltration of the transmural vessel wall). TMA is strongly associated with histological chronicity indices; vasculopathy or vasculitis are related to histological activity indices [ 157 , 158 ].

Clinically, patients with acute TMA may present with arterial hypertension, elevated serum creatinine, microangiopathic hemolytic anemia (presence of schistocytes) and thrombocytopenia. TMA might be suspected in patients with difficult to control arterial hypertension, dysmorphic hematuria and mild or moderate proteinuria (usually <1.5 g/24 h). In case of higher proteinuria, usually glomerulonephritis coexists. Histological findings include wall edema, obliteration or narrowing of the vascular lumen, presence of thrombi in intrarenal vessels of different vascular calibers (acute phase), arterial intimal fibrous hyperplasia, a thyroid-like tubular appearance (pseudo thyroid), an onion appearance, atherosclerosis, arteriolar occlusions and focal cortical atrophy (chronic phase). The prevalence of these findings in the biopsies of patients with LN is 10–39.5% [ 159 , 160 , 161 , 162 ]. The presence of TMA in renal biopsy is considered an isolated marker of poor prognosis in patients with LN, especially when it is associated with class IV [ 160 , 161 , 162 , 163 , 164 , 165 , 166 ]. Regarding treatment, there are no RCTs. An observational study suggested the benefits of anticoagulation therapy with warfarin, but the effects on renal outcomes are unclear [ 167 ]. In addition to low-dose aspirin, anticoagulation therapy may be considered according to the aPL antibody profile and the risk of adverse events. Treatment of LN and nephroprotective measures (especially ACE inhibitors) are essential. Drugs acting on the mTORR pathway (sirolimus) or on the complement system could represent future treatment options [ 168 , 169 ]. Calcineurin inhibitors should be avoided in patients with TMA [ 82 ]. KDIGO 2024 proposed an specific management fo lupus nephritis and TMA [ 170 ].

Involvement of the tubulointerstitial compartment

Tubulointerstitial disease with or without immune deposits along the tubular basement membrane is a common finding in LN patients. In most patients, it is associated with concomitant glomerular disease, and may be a consequence of glomerular lesions. There is a correlation between glomerular activity and infiltration of interstitial inflammatory cells and between chronic glomerular lesions and tubular atrophy and interstitial fibrosis [ 171 , 172 , 173 , 174 ]. Interstitial infiltration, tubular atrophy and interstitial fibrosis are independent risk factors for poor prognosis in patients with LN. The severity of tubulointerstitial involvement correlates with the presence of hypertension, baseline serum creatinine, proteinuria, and progressive worsening of renal function. The presence of tubular atrophy and interstitial fibrosis is associated with a twofold increased risk of developing end-stage CKD [ 172 , 173 , 175 ]. It is important to emphasize the risk of tubulointerstitial toxicity caused by CsA and TAC [ 82 ].

Management of chronic kidney disease

Despite treatment, 10% to 30% of patients with LN progress to end-stage CKD, which can be treated with hemodialysis, peritoneal dialysis, or kidney transplantation. Even small elevations in serum creatinine represent significant kidney damage. Besides elevated creatinine, the presence of proteinuria is also associated with worse long-term renal outcomes. In addition to immunosuppressive treatment, patients should receive guidance and nephroprotective and cardioprotective therapies aiming at prolonging renal survival and decreasing cardiovascular risk. Proteinuria reduction is important, as it reflects disease control, and reduces glomerular hypertension, and podocyte damage (probably a major factor in glomerular scarring). Most studies suggest that end-stage renal disease in patients with LN can be largely prevented if proteinuria is reduced to levels below 0.5 g/24 h. Furthermore, progression is slowed if proteinuria is reduced to levels below 1–1.5 g/24 h [ 33 ].

Kidney transplantation

Patients with LN who undergo kidney transplantation have lower mortality than patients with SLE and CKD who remain on renal replacement therapy [ 176 ]. The outcomes are similar to those patients who underwent transplantation for other causes of CKD [ 177 ]. Thus, kidney transplantation should be considered in patients with end-stage kidney disease as soon as disease activity is controlled [ 33 ]. The best long-term results in preemptive transplantation (before the initiation of renal replacement therapy) highlight the importance of early collaboration with the transplant team to facilitate this procedure [ 178 ].

Recurrence of LN in the transplanted kidney is uncommon, occurring in up to 10% of cases. The presence of aPL antibodies (including anti-beta2-glycoprotein I IgA antibodies) or APS, is associated with worse transplant outcomes and an increased risk of thrombosis and graft loss [ 179 , 180 , 181 ].

Contraception and management of pregnancy in women with LN

Pregnancies in SLE patients are considered of high risk, with increased maternal and fetal morbidity. Of note, a Brazilian study demonstrated that more than 80% of pregnancies in SLE patients are unplanned, justifying the importance of addressing this topic early with patients and families [ 182 ]. Also, pregnancy planning is essential for better maternal an fetal outcomes, and patients with LN should be advised to avoid pregnancy while nephritis is active and for at least 6 months after disease control. Pregnancy should be contraindicated in any of the following conditions: stroke in the last 6 months; pulmonary arterial hypertension; severe restrictive lung disease; CKD classes 3, 4, and 5; heart failure or severe valvular heart disease; and previous episode of severe preeclampsia or HELLP syndrome despite adequate treatment [ 183 , 184 , 185 ].

Contraception should be prescribed for patients with pregnancy contraindications, for those with active disease or on teratogenic drugs and for women who do not wish to become pregnant. Available methods include hormonal (progestogen) or cooper intrauterine device (IUD); oral progestogen (desogestrel or drospirenone); intramuscular medroxyprogesterone; or a progestogen contraceptive implant. The use of oral contraceptives containing estrogens can be used in the absence of nephrotic syndrome, if antiphospholipid antibodies are negative, and with low lupus disease activity [ 185 , 186 ].

Before conception, medication should be reconciled to medications compatible with pregnancy. HCQ should be maintained during pregnancy and lactation, as its discontinuation is associated with a greater risk of maternal–fetal complications [ 57 , 187 ]. In patients with LN, the immunosupressants AZA, TAC, and CsA are compatible with pregnancy and breastfeeding. GC should be used at the lowest dose necessary to control disease activity [ 188 ]. Patients with a history of LN in the last 5 years and receiving maintenance therapy for inactive disease should continue immunosuppressive therapy during pregnancy to prevent LN recurrence. Patients with active LN during pregnancy should also receive immunosuppressive drugs to help control the disease and minimize the use of CEs.

The differential diagnosis between preeclampsia and active LN is challenging, especially when proteinuria and/or arterial hypertension are present. The following factors favor the diagnosis of LN: altered urinary sediment, especially in the presence of dysmorphic hematuria; positive anti-dsDNA; complement consumption; and disease activity in other organs and systems [ 189 ]. To support the hypothesis of preeclampsia these factors are relevant: elevated uric acid (>5.5 mg/dL) and an elevated sFLT-1/PLGF ratio [ 189 , 190 ]. There may be concomitant LN and preeclampsia, and the diagnosis of each condition is important for appropriate treatment since active LN indicates the need for immunosuppression, while preeclampsia requires an efficient BP control and/or to consider the delivery.

The use of low dose aspirin (75–150 mg/day), starting before 16 weeks of pregnancy, is associated with a reduced risk of preeclampsia and preterm birth and is indicated for all SLE pregnant women [ 191 , 192 , 193 , 194 , 195 ]. A calcium rich diet (1 g/day) or calcium supplementation in case of insufficient diet is associated with a 55% reduction in the risk of preeclampsia and its maternal and fetal consequences [ 196 ]. Adequate levels of vitamin D are important for maintaining bone mass and preventing osteoporosis.

Prophylactic heparin (enoxaparin 40 mg/day or equivalent) combined with low-dose aspirin is indicated for pregnant women with obstetric APS and may be considered for pregnant women at high risk of thromboembolic events, such as in the presence of high-risk aPL antibodies or in those with active LN and proteinuria >1 g/day [ 185 , 197 ].

The present consensus aimed to review the main evidence and updates on the treatment of LN, considering the particularities of Brazilian reality. Brazil, a country with continental dimensions, exhibits significant socioeconomic disparities that might be taken into consideration. The analyses performed, including efficacy, safety, values and preferences, costs, equity, acceptability and feasibility, were considered in the decision-making process. Since the last SBR consensus for the treatment of LN in 2015 [ 4 ], there were notable advances in both concepts and approaches to the diagnosis and treatment of LN. Besides updating LN treatment, this consensus brings to light Brazilian contributions for the management of LN patients.

Regarding LN diagnosis, kidney biopsy is considered the gold standard, as it allows the evaluation of histological classes and parameters of activity and chronicity, supports differential diagnosis and guides treatment. However, accessibility to kidney biopsy is limited in Brazil and the use of clinical and laboratorial parameters remains the mainstay for diagnosis in most regions of our country. Of note, an instrument developed in Brazil in order to differentiate LN classes was recently published and can help clinical decisions if kidney biopsy is not available [ 36 ].

Assessment of proteinuria is essential in the management of LN since early reduction in proteinuria is a predictor of renal response. Two important LN cohorts (Euro-Lupus and MAINTAIN) have shown that 1-year proteinuria level is the best predictor of long-term renal outcome [ 37 , 38 ]. This finding was confirmed by two Brazilian studies including patients in real life situation with severe disease and distinct histological classes, race, gender and anti-dsDNA profiles [ 40 , 41 ]. Highlighting the importance of proteinuria in the evaluation of renal response, and in line with international literature, this consensus set the definition of Target Renal Response (TRR), which consists of proteinuria reduction targets at 3, 6 and 12 months, along with preserved renal function. TRR is an easy and effective way to evaluate renal response. The target of proteinuria <0.8 g/day at 12 months was defined according to data from Brazilian patients [ 40 , 41 ].

Our first recommendation is that HCQ should be prescribed to all SLE patients, except if contraindicated. More sensitive tests, such as OCT-SD, are recommended for detecting early retinal toxicity, but accessibility to them is limited in Brazil. Therefore, avoiding excessive HCQ doses is important to prevent retinal toxicity. Dose of HCQ should be adjusted for real body weight (5 mg/kg/day, maximum 400 mg/day). However, for obese patients (BMI ≥ 30 kg/m 2 ), dose of HCQ should be adjusted for ideal body weight (maximum 400 mg/day), as suggested by a recent Brazilian study [ 59 ].

Similarly to other international recommendations, this consensus strongly recommends that glucocorticoids should be used at the lowest dose and for the minimal necessary period, in order to prevent damage accrual. Using lower doses of GC, both for induction and maintenance [ 67 , 68 ], and reaching lower doses in 3 to 6 months is extremely important to limit damage in these patients [ 65 , 66 ].

For induction treatment, either MMF or CYC Euro-Lupus can be used as first-line treatment, as the main randomized studies showed similar efficacy between the two drugs in controlling LN activity [ 69 , 70 , 73 , 74 , 75 , 76 , 77 ]. MMF was recently incorporated into the treatment of LN by the Public Health System in Brazil, which simplifies patients’ access to medication. IV CYC is preferred for non-adherent patients to oral medication and CYC NIH should be reserved for patients with more severe forms of LN due to higher CYC cumulative doses and adverse events, including infertility.

Although new therapies have demonstrated benefits in patients with LN in RCTs, their use was considered conditional mainly due to their high cost and difficulty of access in our country. BEL was associated with an 11% greater renal response and with reduced relapse of renal activity [ 88 , 89 ]. BEL should be considered in patients with difficulty in reducing GC dose, high risk of progression to damage, associated extrarenal manifestations, high risk of relapse or frequent relapses, and high risk of progression to CKD. The use of multitarget therapy (MMF + TAC) has proven to be an alternative to other therapies [ 83 , 84 , 85 ]. The association of voclosporin with MMF was also associated with greater renal response, but is not approved in Brazil yet and adherence could be a practical problem since daily dose requires a high number of pills [ 97 ].

For maintenance treatment, both MMF and AZA can be used as first-line treatment. MMF is preferred in patients who achieve a good renal response to MMF during the induction phase; however, it is more associated with gastrointestinal intolerance. AZA is easier to administer, generally requires fewer daily pills, is less expensive and is compatible with pregnancy and breastfeeding. The duration of maintenance treatment should be at least of 3 to 5 years. Patients with incomplete response, with multiple previous relapses or with renal damage might need longer periods of immunosuppressive treatment [ 48 ].

For pure class V LN, there is scarce literature data since it comprises about 10 to 20% of LN patients [ 115 ]. This consensus recommends the use of GC and immunosuppressants for the treatment of class V LN. Nephroprotective measures, blood pressure control and use of antiproteinuric drugs are essential to control proteinuria in class V LN.

Nephroprotective measures should also be emphasized to all LN patients since they are associated with better renal outcome [ 33 ]. A Brazilian study showed that a tightly controlled renoprotective protocol is effective in reducing persistent proteinuria in LN [ 120 ], which can avoid further unnecessary increases in immunosuppression due to uncontrolled proteinuria. Traditional nephroprotective measures include blood pressure control, renin-angiotensin blockage, low salt diet, smoking cessation, avoidance of nephrotoxic drugs. Despite the scarce evidence in LN, iSGLT2 has been shown to play important nephroprotective and cardioprotective roles in other diseases [ 127 , 128 , 129 ], and is also promising in LN.

Comparing with other published guidelines for LN, the II Brazilian Consensus for LN presents some similarities and differences. KDIGO 2024 [ 170 ] and Eular 2023 [ 198 ] have subtle differences in the definition of renal response target remission, indications of kidney biopsy and strategies of treatment. As mentioned above, in the present consensus, TRR was based in international and Brazilian studies. Regarding treatment, all guidelines reinforced the use of HCQ and low doses of GCs. Both KDIGO 2024 [ 170 ] and Eular 2023 [ 198 ] considered MMF, CYC, multitarget therapies with BEL + MMF or CYC and MMF + TAC as initial therapy in LN. In the II Brazilian Consensus, economic factors and restricted access to BEL and TAC currently positioned these medications as conditional, taking also into consideration patients characteristics. Another interesting point, KDIGO 2024 [ 170 ] and the II Brazilian Consensus emphasizes the treatment of Class V nephritis and adjunctive measures beyond immunosuppression. Altogether, all documents provide an excellent guidance to the growing complexity of LN management and the clinical impact of differences between these guidelines should be analyzed in future studies.

The main limitation of this manuscript is the lack of inclusion of nephrologists and the patients’ perspective on LN treatment, which must be in the agenda in future updates of the guideline and consensus. On the other hand, this consensus has several strengths, including: systematic review and GRADE methodology; rheumatologists with experience in the diagnosis and treatment of LN; decision-making based in important variables (efficacy, safety, values and preferences, costs, equity, acceptability and feasibility) considering the reality of Brazil; discussion of both immunosuppressive treatment and adjunctive measures beyond immunosuppression in all stages of LN; and the proposal of a treatment flowchart for LN.

In the future, there are several additional therapeutics currently being evaluated for the treatment of LN and we expect more patients from Latin America to be included in studies with different ethnicities, studies with pharmacoeconomic analyses, personalized treatments according to biomarkers and histological findings, long-term results with multitarget therapies, and new molecules in phase III/IV studies of LN (obinutuzumab, JAK inhibitors, others).

This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil. However, the autonomy of health professionals must be respected and ensured in relation to the different therapeutic options when based on scientific evidence.

Data availability

All data generated or analysed during this study are included in this published article [and its supplementary information files].

Fanouriakis A, Tziolos N, Bertsias G, Boumpas D. Update οn the diagnosis and management of systemic lupus erythematosus. Ann Rheum Dis. 2021;80(1):14–21.

Article PubMed Google Scholar

Vilar MJ, Sato EI. Estimating the incidence of systemic lupus erythematosus in a tropical region (Natal, Brazil). Lupus. 2002;11(8):528–32.

Klumb E, Scheinberg M, Souza V, Xavier R, Azevedo V, McElwee E, et al. The landscape of systemic lupus erythematosus in Brazil: an expert panel review and recommendations. Lupus 2021;30:1684–95.

Article PubMed PubMed Central Google Scholar

Klumb EM, Silva CA, Lanna CC, Sato EI, Borba EF, Brenol JC, et al. Consensus of the Brazilian Society of Rheumatology for the diagnosis, management and treatment of lupus nephritis. Rev Bras Reumatol 2015;55:1–21.

Moberg J, Oxman A, Rosenbaum S, Schünemann H, Guyatt G, Flottorp S, et al. The GRADE Evidence to Decision (EtD) framework for health system and public health decisions. Health Res Policy Syst 2018;16:45.

Gatto M, Zen M, Iaccarino L, Doria A. New therapeutic strategies in systemic lupus erythematosus management. Nat Rev Rheumatol. 2019;15(1):30–48.

Article CAS PubMed Google Scholar

Gladman D, Ibañez D, Ruiz I, Urowitz M. Recommendations for frequency of visits to monitor systemic lupus erythematosus in asymptomatic patients: data from an observational cohort study. J Rheumatol. 2013;40(5):630–33.

Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken) 2012;64:797–808.

Christopher-Stine L, Siedner M, Lin J, Haas M, Parekh H, Petri M, et al. Renal biopsy in lupus patients with low levels of proteinuria. J Rheumatol 2007;34:332–35.

PubMed Google Scholar

Zabaleta-Lanz M, Muñoz L, Tapanes F, Vargas-Arenas R, Daboin I, Barrios Y, et al. Further description of early clinically silent lupus nephritis. Lupus 2006;15:845–51.

Medina-Rosas J, Yap K, Anderson M, Su J, Touma Z. Utility of urinary protein-creatinine ratio and protein content in a 24-hour urine collection in systemic lupus erythematosus: a systematic review and meta-analysis. Arthritis Care Res. 2016;68(9):1310–19.

Article CAS Google Scholar

Choi I, Park J, Lee E, Song Y, Lee E. Random spot urine protein to creatinine ratio is a reliable measure of proteinuria in lupus nephritis in Koreans. Clin Exp Rheumatol. 2013;31(4):584–88.

Marques G, Cotovio P, Ferrer F, Silva C, Botelho C, Lopes K, et al. Random spot urine protein/creatinine ratio: a reliable method for monitoring lupus nephritis? Clin Kidney J 2013;6:590–94.

Article Google Scholar

McCarty G, Rice J, Bembe M, Pisetsky D. Independent expression of autoantibodies in systemic lupus erythematosus. J Rheumatol. 1982;9(5):691–95.

CAS PubMed Google Scholar

Moroni G, Radice A, Giammarresi G, Quaglini S, Gallelli B, Leoni A, et al. Are laboratory tests useful for monitoring the activity of lupus nephritis? A 6-year prospective study in a cohort of 228 patients with lupus nephritis. Ann Rheum Dis 2009;68:234–37.

Orbai A, Truedsson L, Sturfelt G, Nived O, Fang H, Alarcón G, et al. Anti-C1q antibodies in systemic lupus erythematosus. Lupus 2015;24:42–49.

Bootsma H, Spronk P, Derksen R, de Boer G, Wolters-Dicke H, Hermans J, et al. Prevention of relapses in systemic lupus erythematosus. Lancet (London, England) 1995;345:1595–99.

van Vollenhoven RF, Mosca M, Bertsias G, Isenberg D, Kuhn A, Lerstrom K, et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis 2014;73:958–67.

Hung W, Chen Y, Lan J, Chen H, Chen Y, Chen D, et al. Antinucleosome antibodies as a potential biomarker for the evaluation of renal pathological activity in patients with proliferative lupus nephritis. Lupus 2011;20:1404–10.

Do Nascimento AP, Dos Santos Trindade Viana V, de Abreu Testagrossa L, Leon EP, Borba EF, Barros RT, et al. Antibodies to ribosomal P proteins: a potential serologic marker for lupus membranous glomerulonephritis. Arthritis Rheum 2006;54:1568–72.

de Macedo PA, Borba EF, Viana VD, Leon EP, de Abreu Testagrossa L, Barros RT, et al. Antibodies to ribosomal P proteins in lupus nephritis: a surrogate marker for a better renal survival? Autoimmun Rev 2011;10:126–30.

Wang S, Shang J, Xiao J, Zhao Z. Clinicopathologic characteristics and outcomes of lupus nephritis with positive antineutrophil cytoplasmic antibody. Ren Fail. 2020;42(1):244–54.

Article CAS PubMed PubMed Central Google Scholar

Turner-Stokes T, Wilson H, Morreale M, Nunes A, Cairns T, Cook H, et al. Positive antineutrophil cytoplasmic antibody serology in patients with lupus nephritis is associated with distinct histopathologic features on renal biopsy. Kidney Int 2017;92:1223–31.

Rosenkranz A, Tesar V. Lupus nephritis and ANCA-associated vasculitis: towards precision medicine? Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association - European Renal Association. Nephrol Dial Transplant. 2021;36(Suppl 2):37–43.

Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 2004;15:241–50.

Bajema I, Wilhelmus S, Alpers C, Bruijn J, Colvin R, Cook H, et al. Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. Kidney Int 2018;93:789–96.

Austin H, Muenz L, Joyce K, Antonovych T, Balow J. Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome. Kidney Int. 1984;25(4):689–95.

Parodis I, Tamirou F, Houssiau F. Prediction of prognosis and renal outcome in lupus nephritis. Lupus Sci Med. 2020;7(1):e000389.

Fanouriakis A, Kostopoulou M, Cheema K, Anders H, Aringer M, Bajema I, et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis 2020;79:713–23.

Parikh S, Alvarado A, Malvar A, Rovin B. The kidney biopsy in lupus nephritis: past, present, and future. Semin Nephrol. 2015;35(5):465–77.

Anders H, Saxena R, Zhao M, Parodis I, Salmon J, Mohan C. Lupus nephritis. Nat Rev Dis Primers. 2020;6(1):7.

Mejia-Vilet J, Malvar A, Arazi A, Rovin B. The lupus nephritis management renaissance. Kidney Int. 2022;101(2):242–55.

KDIGO. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int. 2021;100(4S):S1–S276.

Parikh SV, Almaani S, Brodsky S, Rovin BH. Update on lupus nephritis: core curriculum 2020. Am J Kidney Dis. 2020;76(2):265–81.

Mavragani C, Fragoulis G, Somarakis G, Drosos A, Tzioufas A, Moutsopoulos H. Clinical and laboratory predictors of distinct histopathogical features of lupus nephritis. Medicine (Baltimore). 2015;94(21):e829.

Silaide de Araújo Júnior A, Sato EI, Silva de Souza AW, Jennings F, Mastroianni Kirsztajn G, Sesso R, et al. Development of an instrument to predict proliferative histological class in lupus nephritis based on clinical and laboratory data. Lupus 2023;32:216–24.

Dall’Era M, Cisternas M, Smilek D, Straub L, Houssiau F, Cervera R, et al. Predictors of long-term renal outcome in lupus nephritis trials: lessons learned from the Euro-Lupus Nephritis cohort. Arthritis Rheumatol 2015;67:1305–13.

Tamirou F, Lauwerys B, Dall’Era M, Mackay M, Rovin B, Cervera R, et al. A proteinuria cut-off level of 0.7 g/day after 12 months of treatment best predicts long-term renal outcome in lupus nephritis: data from the MAINTAIN Nephritis Trial. Lupus Sci Med 2015;2:e000123.

Tamirou F, D’Cruz D, Sangle S, Remy P, Vasconcelos C, Fiehn C, et al. Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis. Ann Rheum Dis 2016;75:526–31.

Ugolini-Lopes M, Seguro L, Castro M, Daffre D, Lopes A, Borba E, et al. Early proteinuria response: a valid real-life situation predictor of long-term lupus renal outcome in an ethnically diverse group with severe biopsy-proven nephritis? Lupus Sci Med 2017;4:e000213.

Braga F, Medeiros M, Viana-Junior A, Sousa Lima M, Barros L, Pontes M, et al. Proteinuria and serum creatinine after 12 months of treatment for lupus nephritis as predictors of long-term renal outcome: a case-control study. Adv Rheumatol 2022;62:2.

Dall’Era M, Stone D, Levesque V, Cisternas M, Wofsy D. Identification of biomarkers that predict response to treatment of lupus nephritis with mycophenolate mofetil or pulse cyclophosphamide. Arthritis Care Res (Hoboken). 2011;63(3):351–57.

Dall’Era M, Levesque V, Solomons N, Truman M, Wofsy D. Identification of clinical and serological factors during induction treatment of lupus nephritis that are associated with renal outcome. Lupus Sci Med. 2015;2(1):e000089.

Houssiau F, Vasconcelos C, D’Cruz D, Sebastiani G, de Ramon Garrido E, Danieli M, et al. The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. Ann Rheum Dis 2010;69:61–64.

Korbet S, Lewis E. Severe lupus nephritis: the predictive value of a ≥ 50% reduction in proteinuria at 6 months. Nephrol Dial Transplant. 2013;28(9):2313–18.

Houssiau F, Vasconcelos C, D’Cruz D, Sebastiani G, de Ramon Garrido E, Danieli M, et al. Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis: lessons from long-term followup of patients in the Euro-Lupus Nephritis Trial. Arthritis Rheum 2004;50:3934–40.

Touma Z, Urowitz M, Ibañez D, Gladman D. Time to recovery from proteinuria in patients with lupus nephritis receiving standard treatment. J Rheumatol. 2014;41(4):688–97.

Jourde-Chiche N, Costedoat-Chalumeau N, Baumstarck K, Loundou A, Bouillet L, Burtey S, et al. Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): results of a multicentre randomised controlled trial. Ann Rheum Dis 2022;81:1420–27.

Moroni G, Raffiotta F, Ponticelli C. Remission and withdrawal of therapy in lupus nephritis. J Nephrol. 2016;29(4):559–65.

Zickert A, Sundelin B, Svenungsson E, Gunnarsson I. Role of early repeated renal biopsies in lupus nephritis. Lupus Sci Med. 2014;1(1):559–65.

De Rosa M, Azzato F, Toblli J, De Rosa G, Fuentes F, Nagaraja H, et al. A prospective observational cohort study highlights kidney biopsy findings of lupus nephritis patients in remission who flare following withdrawal of maintenance therapy. Kidney Int 2018;94:788–94.

Malvar A, Pirruccio P, Alberton V, Lococo B, Recalde C, Fazini B, et al. Histologic versus clinical remission in proliferative lupus nephritis. Nephrol Dial Transplant 2017;32:1338–44.

Yo J, Barbour T, Nicholls K. Management of refractory lupus nephritis: challenges and solutions. Open Access Rheumatol. 2019;11:179–88.

Cervera R, Mosca M, Ríos-Garcés R, Espinosa G, Trujillo H, Bada T, et al. Treatment for refractory lupus nephritis: rituximab vs triple target therapy. Autoimmun Rev 2019;18:102406.

Kronbichler A, Brezina B, Gauckler P, Quintana L, Jayne D. Refractory lupus nephritis: when, why and how to treat. Autoimmun Rev. 2019;18(5):510–18.

Ali A, Abdelaziz T, Behiry M. The prevalence and causes of non-adherence to immunosuppressive medications in patients with lupus nephritis flares. Curr Rheumatol Rev. 2020;16(3):245–48.

Dos Reis Neto ET, Kakehasi AM, de Medeiros Pinheiro M, Ferreira GA, Marques CDL, da Mota LMH, et al. Revisiting hydroxychloroquine and chloroquine for patients with chronic immunity-mediated inflammatory rheumatic diseases. Adv Rheumatol 2020;60:32.

Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 Revision). Ophthalmology. 2016;123(6):1386–94.

Pedrosa TN, Pasoto SG, Aikawa NE, Yuki EF, Borba EF, Filho JCF, et al. Understanding the dynamics of hydroxychloroquine blood levels in lupus nephritis. Lupus 2020;29:560–68.

Zanetti C, Pedrosa T, Kupa L, Aikawa N, Borba E, Vendramini M, et al. Hydroxychloroquine blood levels in stable lupus nephritis under low dose (2-3 mg/kg/day): 12-month prospective randomized controlled trial. Clin Rheumatol 2021;40:2745–51.

Blanchet B, Jallouli M, Allard M, Ghillani-Dalbin P, Galicier L, Aumaître O, et al. Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence. Arthritis Res Ther 2020;22:223.

Petri M, Konig M, Li J, Goldman D. Association of higher hydroxychloroquine blood levels with reduced thrombosis risk in systemic lupus erythematosus. Arthritis Rheumatol. 2021;73(6):997–1004.

Rosenbaum J, Costenbader K, Desmarais J, Ginzler E, Fett N, Goodman S, et al. American College of Rheumatology, American Academy of Dermatology, Rheumatologic Dermatology Society, and American Academy of Ophthalmology 2020 joint statement on hydroxychloroquine use with respect to retinal toxicity. Arthritis Rheumatol 2021;73:908–11.

Tselios K, Gladman DD, Al-Sheikh H, Su J, Urowitz MB. Medium versus high initial prednisone dose for remission induction in lupus nephritis: a propensity score-matched analysis. Arthritis Care Res. 2022;74(9):1451–58.

Gladman D, Urowitz M, Rahman P, Ibañez D, Tam L. Accrual of organ damage over time in patients with systemic lupus erythematosus. J Rheumatol. 2003;30(9):1955–59.

Urowitz M, Gladman D, Ibañez D, Fortin P, Bae S, Gordon C, et al. Evolution of disease burden over five years in a multicenter inception systemic lupus erythematosus cohort. Arthritis Care Res 2012;64:132–37.

Ruiz-Irastorza G, Danza A, Perales I, Villar I, Garcia M, Delgado S, et al. Prednisone in lupus nephritis: how much is enough? Autoimmun Rev 2014;13:206–14.

Ruiz-Irastorza G, Ugarte A, Saint-Pastou Terrier C, Lazaro E, Iza A, Couzi L, et al. Repeated pulses of methyl-prednisolone with reduced doses of prednisone improve the outcome of class III, IV and V lupus nephritis: an observational comparative study of the Lupus-Cruces and lupus-Bordeaux cohorts. Autoimmun Rev 2017;16:826–32.

Sedhain A, Hada R, Agrawal R, Bhattarai G, Baral A. Low dose mycophenolate mofetil versus cyclophosphamide in the induction therapy of lupus nephritis in Nepalese population: a randomized control trial. BMC Nephrol. 2018;19(1):175.

Rathi M, Goyal A, Jaryal A, Sharma A, Gupta P, Ramachandran R, et al. Comparison of low-dose intravenous cyclophosphamide with oral mycophenolate mofetil in the treatment of lupus nephritis. Kidney Intern 2016;89:235–42.

Anutrakulchai S, Panaput T, Wongchinsri J, Chaishayanon S, Satirapoj B, Traitanon O, et al. A multicentre, randomised controlled study of enteric-coated mycophenolate sodium for the treatment of relapsed or resistant proliferative lupus nephritis: an Asian experience. Lupus Sci Med 2016;3:e000120.

Li X, Ren H, Zhang Q, Zhang W, Wu X, Xu Y, et al. Mycophenolate mofetil or tacrolimus compared with intravenous cyclophosphamide in the induction treatment for active lupus nephritis. Nephrol Dial Transplant 2012;27:1467–72.

Appel G, Contreras G, Dooley M, Ginzler E, Isenberg D, Jayne D, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 2009;20:1103–12.

Wang J, Hu W, Xie H, Zhang H, Chen H, Zeng C, et al. Induction therapies for class IV lupus nephritis with non-inflammatory necrotizing vasculopathy: mycophenolate mofetil or intravenous cyclophosphamide. Lupus 2007;16:707–12.

Ong L, Hooi L, Lim T, Goh B, Ahmad G, Ghazalli R, et al. Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis. Nephrology (Carlton) 2005;10:504–10.

Ginzler E, Dooley M, Aranow C, Kim M, Buyon J, Merrill J, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. New Eng J Med 2005;353:2219–28.

Houssiau F, Vasconcelos C, D’Cruz D, Sebastiani G, Garrido EER, Danieli M, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum 2002;46:2121–31.

Isenberg D, Appel G, Contreras G, Dooley M, Ginzler E, Jayne D, et al. Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study. Rheumatology (Oxford) 2010;49:129–40.

Zeher M, Doria A, Lan J, Aroca G, Jayne D, Boletis I, et al. Efficacy and safety of enteric-coated mycophenolate sodium in combination with two glucocorticoid regimens for the treatment of active lupus nephritis. Lupus 2011;20:1484–93.

Walsh M, Solomons N, Lisk L, Jayne DR. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis with poor kidney function: a subgroup analysis of the Aspreva Lupus Management Study. Am J Kidney Dis. 2013;61(5):710–15.

Peleg Y, Bomback A, Radhakrishnan J. The evolving role of calcineurin inhibitors in treating lupus nephritis. Clin J Am Soc Nephrol. 2020;15(7):1066–72.

Farouk S, Rein J. The many faces of calcineurin inhibitor toxicity-what the FK? Adv Chronic Kidney Dis. 2020;27(1):56–66.

Bao H, Liu Z, Xie H, Hu W, Zhang H, Li L. Successful treatment of class V+IV lupus nephritis with multitarget therapy. J Am Soc Nephrol. 2008;19(10):2001–10.

Liu Z, Zhang H, Liu Z, Xing C, Fu P, Ni Z, et al. Multitarget therapy for induction treatment of lupus nephritis: a randomized trial. Ann Intern Med 2015;162:18–26.

Lee Y, Song G. Multitarget therapy versus monotherapy as induction treatment for lupus nephritis: a meta-analysis of randomized controlled trials. Lupus. 2022;31(12):1468–76.

Jesus D, Rodrigues M, da Silva J, Inês L. Multitarget therapy of mycophenolate mofetil and cyclosporine A for induction treatment of refractory lupus nephritis. Lupus. 2018;27(8):1358–62.

Kasitanon N, Boripatkosol P, Louthrenoo W. Response to combination of mycophenolate mofetil, cyclosporin A and corticosteroid treatment in lupus nephritis patients with persistent proteinuria. Int J Rheum Dis. 2018;21(1):200–07.

Furie R, Rovin B, Houssiau F, Malvar A, Teng Y, Contreras G, et al. Two-year, randomized, controlled trial of belimumab in lupus nephritis. N Engl J Med 2020;383:1117–28.

Rovin B, Furie R, Teng Y, Contreras G, Malvar A, Yu X, et al. A secondary analysis of the Belimumab International Study in lupus nephritis trial examined effects of belimumab on kidney outcomes and preservation of kidney function in patients with lupus nephritis. Kidney Int 2022;101:403–13.

Furie R, Petri M, Zamani O, Cervera R, Wallace D, Tegzová D, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheumatol 2011;63:3918–30.

Navarra S, Guzmán R, Gallacher A, Hall S, Levy R, Jimenez R, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 2011;377:721–31.

Chen W, Tang X, Liu Q, Chen W, Fu P, Liu F, et al. Short-term outcomes of induction therapy with tacrolimus versus cyclophosphamide for active lupus nephritis: a multicenter randomized clinical trial. Am J Kidney Dis 2011;57:235–44.

Zheng Z, Zhang H, Peng X, Zhang C, Xing C, Xu G, et al. Effect of tacrolimus vs intravenous cyclophosphamide on complete or partial response in patients with lupus nephritis: a randomized clinical trial. JAMA Network Open 2022;5:e224492.

Kamanamool N, Ingsathit A, Rattanasiri S, Ngamjanyaporn P, Kasitanont N, Chawanasuntorapoj R, et al. Comparison of disease activity between tacrolimus and mycophenolate mofetil in lupus nephritis: a randomized controlled trial. Lupus 2018;27:647–56.

Yap D, Yu X, Chen X, Lu F, Chen N, Li X, et al. Pilot 24 month study to compare mycophenolate mofetil and tacrolimus in the treatment of membranous lupus nephritis with nephrotic syndrome. Nephrology (Carlton) 2012;17:352–57.

Rovin B, Solomons N, Pendergraft W, Dooley M, Tumlin J, Romero-Diaz J, et al. A randomized, controlled double-blind study comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis. Kidney Int 2019;95:219–31.

Rovin B, Teng Y, Ginzler E, Arriens C, Casterm D, Romero-Diaz J, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2021;397:2070–80.

Zavada J, Pesickova S, Rysava R, Olejarova M, Horák P, Hrncír Z, et al. Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study. Lupus 2010;19:1281–89.

Remer C, Weisman M, Wallace D. Benefits of leflunomide in systemic lupus erythematosus: a pilot observational study. Lupus. 2001;10(7):480–83.

Tam L, Li E, Wong C, Lam C, Szeto C. Double-blind, randomized, placebo-controlled pilot study of leflunomide in systemic lupus erythematosus. Lupus. 2004;13(8):601–04.

Wang H, Cui T, Hou F, Ni Z, Chen X, Lu F, et al. Induction treatment of proliferative lupus nephritis with leflunomide combined with prednisone: a prospective multi-centre observational study. Lupus 2008;17:638–44.

Tam L, Li E, Wong C, Lam C, Li W, Szeto C. Safety and efficacy of leflunomide in the treatment of lupus nephritis refractory or intolerant to traditional immunosuppressive therapy: an open label trial. Ann Rheum Dis. 2006;65(3):417–18.

Zhang M, Qi C, Zha Y, Chen J, Luo P, Wang L, et al. Leflunomide versus cyclophosphamide in the induction treatment of proliferative lupus nephritis in Chinese patients: a randomized trial. Clin Rheum 2019;38:859–67.

Cao H, Rao Y, Liu L, Lin J, Yang H, Zhang X, et al. The efficacy and safety of leflunomide for the treatment of lupus nephritis in Chinese patients: systematic review and meta-analysis. PloS ONE 2015;10:e0144548.

Burns C. The history of cortisone discovery and development. Rheum Dis Clin North Am. 2016;42(1):1–14.

Gourley M, Austin H, Scott D, Yarboro C, Vaughan E, Muir J, et al. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med 1996;125:549–57.

Illei G, Austin H, Crane M, Collins L, Gourley M, Yarboro C, et al. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med 2001;135:248–57.

Houssiau FA, D’Cruz D, Sangle S, Remy P, Vasconcelos C, Petrovic R, et al. Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial. Ann Rheum Dis 2010;69:2083–89.

Dooley M, Jayne D, Ginzler E, Isenberg D, Olsen N, Wofsy D, et al. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med 2011;365:1886–95.

Maneiro J, Lopez-Canoa N, Salgado E, Gomez-Reino J. Maintenance therapy of lupus nephritis with mycophenolate or azathioprine: systematic review and meta-analysis. Rheumatology (Oxford). 2014;53(5):834–38.

Chen W, Liu Q, Chen W, Tang X, Fu P, Liu F, et al. Outcomes of maintenance therapy with tacrolimus versus azathioprine for active lupus nephritis: a multicenter randomized clinical trial. Lupus 2012;21:944–52.

Moroni G, Doria A, Mosca M, Alberighi O, Ferraccioli G, Todesco S, et al. A randomized pilot trial comparing cyclosporine and azathioprine for maintenance therapy in diffuse lupus nephritis over four years. Clin J Am Soc Nephrol 2006;1:925–32.

Fu Q, Wu C, Dai M, Wang S, Xu J, Dai L, et al. Leflunomide versus azathioprine for maintenance therapy of lupus nephritis: a prospective, multicentre, randomised trial and long-term follow-up. Ann Rheum Dis 2022;81:1549–55.

Contreras G, Pardo V, Leclercq B, Lenz O, Tozman E, O’Nan P, et al. Sequential therapies for proliferative lupus nephritis. N Engl J Med 2004;350:971–80.

Mok C. Membranous nephropathy in systemic lupus erythematosus: a therapeutic enigma. Nat Rev Nephrol. 2009;5(4):212–20.

Sloan R, Schwartz M, Korbet S, Borok R. Long-term outcome in systemic lupus erythematosus membranous glomerulonephritis. Lupus Nephritis Collaborative Study Group. J Am Soc Nephrol. 1996;7(2):299–305.

Ponticelli C, Moroni G, Fornoni A. Lupus membranous nephropathy. Glomerular Dis. 2021;1(1):10–20.

Almaani S, Parikh S. Membranous lupus nephritis: a clinical review. Adv Chronic Kidney Dis. 2019;26(5):393–403.

Austin H, Illei G, Braun M, Balow J. Randomized, controlled trial of prednisone, cyclophosphamide, and cyclosporine in lupus membranous nephropathy. J Am Soc Nephrol. 2009;20(4):901–11.

Castro M, Ugolini-Lopes M, Borba E, Bonfá E, Seguro L. Effectiveness of renoprotective approaches for persistent proteinuria in lupus nephritis: more than just immunosuppression. Lupus. 2018;27(14):2215–19.

Rovin B, Furie R, Latinis K, Looney R, Fervenza F, Sanchez-Guerrero J, et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheumatol 2012;64:1215–26.

Yuan Z, Xie Q, Wu X, Tan B, Zhang X. Rituximab treatment for lupus nephritis: a systematic review. Clinical Invest Med. 2020;43(2):E47–54.

Weidenbusch M, Römmele C, Schröttle A, Anders H. Beyond the LUNAR trial. Efficacy of rituximab in refractory lupus nephritis. Nephrol Dial Transplant. 2013;28(1):106–11.

Bruce IN, Gladman DD, Urowitz MB. Factors associated with refractory renal disease in patients with systemic lupus erythematosus: the role of patient nonadherence. Arthritis Care Res. 2000;13(6):406–08.

Griffin B, Lightstone L. Renoprotective strategies in lupus nephritis: beyond immunosuppression. Lupus. 2013;22(12):1267–73.

Barroso WKS, Rodrigues CIS, Bortolotto LA, Mota-Gomes MA, Brandão AA, Feitosa ADM, et al. Brazilian guidelines of hypertension - 2020. Arq Bras Cardiol 2021;116:516–658.

Morales E, Galindo M. SGLT2 inhibitors in lupus nephropathy, a new therapeutic strategy for nephroprotection. Ann Rheum Dis. 2022.

Heerspink H, Stefánsson B, Correa-Rotter R, Chertow G, Greene T, Hou F, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med 2020;383:1436–46.

Packer M, Anker S, Butler J, Filippatos G, Pocock S, Carson P, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med 2020;383:1413–24.

Bruce IN.‘Not only…but also’: factors that contribute to accelerated atherosclerosis and premature coronary heart disease in systemic lupus erythematosus. Rheumatology (Oxford). 2005;44(12):1492–502.

Grundy S, Stone N, Bailey A, Beam C, Birtcher K, Blumenthal R, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: a Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019;73:e285–e350.

Drosos G, Vedder D, Houben E, Boekel L, Atzeni F, Badreh S, et al. EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome. Ann Rheum Diseases 2022;81:768–79.

Visseren F, Mach F, Smulders Y, Carballo D, Koskinas K, Bäck M, et al. 2021 ESC guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2021;42:3227–337.

Pereira R, Perez M, Paula A, Moreira C, Castro C, Zerbini C, et al. Guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis: an update of Brazilian Society of Rheumatology (2020). Arch Osteoporos 2021;16:49.

Buckley L, Guyatt G, Fink H, Cannon M, Grossman J, Hansen K, et al. 2017 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res 2017;69:1095–110.

Petri M. Epidemiology of the antiphospholipid antibody syndrome. J Autoimmun. 2000;15(2):145–51.

Ünlü O, Zuily S, Erkan D. The clinical significance of antiphospholipid antibodies in systemic lupus erythematosus. Eur J Rheumatol. 2016;3(2):75–84.

Tektonidou MG, Andreoli L, Limper M, Amoura Z, Cervera R, Costedoat-Chalumeau N, et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis 2019;78:1296–304.

Lin R, McDonald G, Jolly T, Batten A, Chacko B. A systematic review of prophylactic anticoagulation in nephrotic syndrome. Kidney Int Rep. 2019;5(4):435–47.

Danza A, Ruiz-Irastorza G. Infection risk in systemic lupus erythematosus patients: susceptibility factors and preventive strategies. Lupus. 2013;22(12):1286–94.

Singh B, Singh S. Systemic lupus erythematosus and infections. Reumatismo. 2020;72(3):154–69.

Oku K, Hamijoyo L, Kasitanon N, Li M, Navarra S, Morand E, et al. Prevention of infective complications in systemic lupus erythematosus: a systematic literature review for the APLAR consensus statements. Int J Rheum Dis 2021;24:880–95.

Santiago M, Leitão B. Prevention of strongyloides hyperinfection syndrome: a rheumatological point of view. Eur J Intern Med. 2009;20(8):744–48.

Schmajuk G, Jafri K, Evans M, Shiboski S, Gianfrancesco M, Izadi Z, et al. Pneumocystis jirovecii pneumonia (PJP) prophylaxis patterns among patients with rheumatic diseases receiving high-risk immunosuppressant drugs. Semin Arthritis Rheum 2019;48:1087–92.

Yeo K, Chen H, Chen Y, Lin C, Chen D, Lai C, et al. Hydroxychloroquine may reduce risk of Pneumocystis pneumonia in lupus patients: a Nationwide, population-based case-control study. BMC Infect Dis 2020;20:112.

Wang W, Lai C, Huang Y, Li T, Tsao Y, Chen W, et al. Pneumocystis jirovecii pneumonia in systemic lupus erythematosus: a nationwide cohort study in Taiwan. Arthritis Care Res 2022;74:1444–50.

Mason A, Anver H, Lwin M, Holroyd C, Faust S, Edwards C. Lupus, vaccinations and COVID-19: what we know now. Lupus. 2021;30(10):1541–52.

Marques C, Kakehasi A, Pinheiro M, Mota L, Albuquerque C, Silva C, et al. High levels of immunosuppression are related to unfavourable outcomes in hospitalised patients with rheumatic diseases and COVID-19: first results of ReumaCoV Brasil registry. RMD Open 2021;7:e001461.

Wadström H, Arkema E, Sjöwall C, Askling J, Simard J. Cervical neoplasia in systemic lupus erythematosus: a nationwide study. Rheumatology (Oxford). 2017;56(4):613–19.

Imunizações SSBd. Calendários de Vacinação SBIm Pacientes Especiais– 2023-2024. 2023–2024.

Feldman CH, Speyer C, Ashby R, L Bermas B, Bhattacharyya S, Chakravarty E, et al. Development of a set of lupus-specific, ambulatory care-sensitive, potentially preventable adverse conditions: a delphi consensus study. Arthritis Care Res 2021;73:146–57.

Tonacio A, Do Nascimento Pedrosa T, Borba E, Aikawa N, Pasoto S, Filho J, et al. Immunogenicity and safety of primary fractional-dose yellow fever vaccine in autoimmune rheumatic diseases. PLoS Negl Trop Dis 2021;15:e0010002.

Valim V, Machado K, Miyamoto S, Pinto A, Rocha P, Serrano E, et al. Planned yellow fever primary vaccination is safe and immunogenic in patients with autoimmune diseases: a prospective non-interventional study. Front Immunol. 2020;11:1382.

Oliva-Damaso N, Payan J, Oliva-Damaso E, Pereda T, Bomback A. Lupus podocytopathy: an overview. Adv Chronic Kidney Dis. 2019;26(5):369–75.

Wang SF, Chen YH, Chen DQ, Liu ZZ, Xu F, Zeng CH, et al. Mesangial proliferative lupus nephritis with podocytopathy: a special entity of lupus nephritis. Lupus 2018;27:303–11.

Bomback AS, Markowitz GS. Lupus podocytopathy: a distinct entity. Clin J Am Soc Nephrol. 2016;11(4):547–48.

Mejía-Vilet JM, Córdova-Sánchez BM, Uribe-Uribe NO, Correa-Rotter R, Morales-Buenrostro LE. Prognostic significance of renal vascular pathology in lupus nephritis. Lupus. 2017;26(10):1042–50.

Banfi G, Bertani T, Boeri V, Faraggiana T, Mazzucco G, Monga G, et al. Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL). Am J Kidney Dis 1991;18:240–48.

Tsumagari T, Fukumoto S, Kinjo M, Tanaka K. Incidence and significance of intrarenal vasculopathies in patients with systemic lupus erythematosus. Hum Pathol. 1985;16(1):43–49.

Strufaldi F, Menezes Neves P, Dias C, Yu L, Woronik V, Cavalcante L, et al. Renal thrombotic microangiopathy associated to worse renal prognosis in lupus nephritis. J Nephrol 2021;34:1147–56.

Song D, Wu L, Wang F, Yang X, Zhu D, Chen M, et al. The spectrum of renal thrombotic microangiopathy in lupus nephritis. Arthritis Res Ther 2013;15:R12.

Barrera-Vargas A, Rosado-Canto R, Merayo-Chalico J, Arreola-Guerra J, Mejía-Vilet J, Correa-Rotter R, et al. Renal thrombotic microangiopathy in proliferative lupus nephritis: risk factors and clinical outcomes: a case-control study. J Clin Rheumatol 2016;22:245–40.

Hu W, Liu Z, Chen H, Zhang H, Li L, Liu Z. Clinical characteristics and prognosis of diffuse proliferative lupus nephritis with thrombotic microangiopathy. Lupus. 2010;19(14):1591–98.

Yu F, Haas M, Glassock R, Zhao M. Redefining lupus nephritis: clinical implications of pathophysiologic subtypes. Nat Rev Nephrol. 2017;13(8):483–95.

Park M, Caselman N, Ulmer S, Weitz I. Complement-mediated thrombotic microangiopathy associated with lupus nephritis. Blood Adv. 2018;2(16):2090–94.

Alkhatib MH, Kant S, Menez S, Lakhani L, Sperati CJ, Fine DM, et al. Thrombotic microangiopathy versus class IV lupus nephritis in systemic lupus erythematosus. J Nephrol 2021;34:1907–13.

Sciascia S, Yazdany J, Dall’Era M, Fenoglio R, Radin M, Aggarwal I, et al. Anticoagulation in patients with concomitant lupus nephritis and thrombotic microangiopathy: a multicentre cohort study. Ann Rheum Dis 2019;78:1004–06.

Gracia-Tello B, Isenberg D. Kidney disease in primary anti-phospholipid antibody syndrome. Rheumatology (Oxford). 2017;56(7):1069–80.

Bienaimé F, Legendre C, Terzi F, Canaud G. Antiphospholipid syndrome and kidney disease. Kidney Int. 2017;91(1):34–44.

KDIGO. KDIGO 2024 clinical practice guideline for the management of LUPUS NEPHRITIS. Kidney Int. 2024;105(1S):S1–S69.

O’Dell JR, Hays RC, Guggenheim SJ, Steigerwald JC. Tubulointerstitial renal disease in systemic lupus erythematosus. Arch Intern Med. 1985;145(11):1996–99.

Wilson P, Kashgarian M, Moeckel G. Interstitial inflammation and interstitial fibrosis and tubular atrophy predict renal survival in lupus nephritis. Clin Kidney J. 2018;11(2):207–18.

Hsieh C, Chang A, Brandt D, Guttikonda R, Utset T, Clark M. Predicting outcomes of lupus nephritis with tubulointerstitial inflammation and scarring. Arthritis Care Res. 2011;63(6):865–74.

Baranowska-Daca E, Choi Y, Barrios R, Nassar G, Suki W, Truong L. Nonlupus nephritides in patients with systemic lupus erythematosus: a comprehensive clinicopathologic study and review of the literature. Hum Pathol. 2001;32(10):1125–35.

Broder A, Mowrey W, Khan H, Jovanovic B, Londono-Jimenez A, Izmirly P, et al. Tubulointerstitial damage predicts end stage renal disease in lupus nephritis with preserved to moderately impaired renal function: a retrospective cohort study. Semin Arthritis Rheum 2018;47:545–51.

Jorge A, Wallace Z, Lu N, Zhang Y, Choi H. Renal transplantation and survival among patients with lupus nephritis: a cohort study. Ann Intern Med. 2019;170(4):240–47.

O’Shaughnessy M, Liu S, Montez-Rath M, Lenihan C, Lafayette R, Winkelmayer W. Kidney transplantation outcomes across GN subtypes in the United States. J Am Soc Nephrol. 2017;28(2):632–44.

Wong T, Goral S. Lupus nephritis and kidney transplantation: where are we today? Adv Chronic Kidney Dis. 2019;26(5):313–22.

Wagenknecht DR, Fastenau DR, Torry RJ, Becker DG, LeFor WM, Carter CB, et al. Risk of early renal allograft failure is increased for patients with antiphospholipid antibodies. Transpl Int 2000;13:S78–81.

Morales J, Serrano M, Martinez-Flores J, Perez D, Serrano A. Antiphospholipid syndrome and renal allograft thrombosis. Transplantation. 2019;103(3):481–86.

Morales JM, Martinez-Flores JA, Serrano M, Castro MJ, Alfaro FJ, García F, et al. Association of early kidney allograft failure with preformed IgA antibodies to β2-glycoprotein I. J Am Soc Nephrol 2015;26:735–45.

Dos Santos FC, Ignacchiti ML, Rodrigues B, Velarde LG, Levy RA, de Jesús GR, et al. Premature rupture of membranes - a cause of foetal complications among lupus: a cohort study, systematic review and meta-analysis. Lupus 2021;30:2042–53.

Lightstone L, Hladunewich M. Lupus nephritis and pregnancy: concerns and management. Semin Nephrol. 2017;37(4):347–53.

Bremme K, Honkanen S, Gunnarsson I, Chaireti R. The presence of lupus nephritis additionally increases the risk of preeclampsia among pregnant women with systemic lupus erythematosus. Lupus. 2021;30(7):1031–38.

Sammaritano LR, Bermas BL, Chakravarty EE, Chambers C, Clowse MEB, Lockshin MD, et al. 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol 2020;72:529–56.

Andreoli L, Bertsias GK, Agmon-Levin N, Brown S, Cervera R, Costedoat-Chalumeau N, et al. EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis 2017;76:476–85.

Dima A, Jurcut C, Chasset F, Felten R, Arnaud L. Hydroxychloroquine in systemic lupus erythematosus: overview of current knowledge. Ther Adv Musculoskelet Dis. 2022;14:14.

Dalal D, Patel K, Patel M. Systemic lupus erythematosus and pregnancy: a brief review. J Obstet Gynaecol India. 2019;69(2):104–09.

Buyon JP, Kalunian KC, Ramsey-Goldman R, Petri MA, Lockshin MD, Ruiz-Irastorza G, et al. Assessing disease activity in SLE patients during pregnancy. Lupus 1999;8:677–84.

Jesús GR, Lacerda MI, Rodrigues BC, Dos Santos FC, Do Nascimento AP, Cristóvão Porto L, et al. Soluble Flt-1, placental growth factor, and vascular endothelial growth factor serum levels to differentiate between active lupus nephritis during pregnancy and preeclampsia. Arthritis Care Res (Hoboken) 2021;73:717–21.

Roberge S, Bujold E, Nicolaides K. Aspirin for the prevention of preterm and term preeclampsia: systematic review and metaanalysis. Am J Obstet Gynecol. 2018;218(3):287–93.

Rolnik DL, O’Gorman N, Roberge S, Bujold E, Hyett J, Uzan S, et al. Early screening and prevention of preterm pre-eclampsia with aspirin: time for clinical implementation. Ultrasound Obstet Gynecol 2017;50:551–56.

Atallah A, Lecarpentier E, Goffinet F, Doret-Dion M, Gaucherand P, Tsatsaris V. Aspirin for prevention of preeclampsia. Drugs. 2017;77(17):1819–31.

Ren Y, Zhao Y, Yang X, Shen C, Luo H. Application of low dose aspirin in pre-eclampsia. Front Med Lausanne. 2023;10:1111371.

Rolnik DL, Wright D, Poon LC, O’Gorman N, Syngelaki A, de Paco Matallana C, et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med 2017;377:613–22.

Hofmeyr GJ, Atallah AN, Duley L. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev. 2006;(3):CD001059.

Bramham K, Seed PT, Lightstone L, Nelson-Piercy C, Gill C, Webster P, et al. Diagnostic and predictive biomarkers for pre-eclampsia in patients with established hypertension and chronic kidney disease. Kidney Int 2016;89:874–85.

Fanouriakis A, Kostopoulou M, Andersen J, Aringer M, Arnaud L, Bae S, et al. EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis. 2024;83:15–29.

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Acknowledgements

Not applicable.

The study was funded by Brazilian Society of Rheumatology. This guideline and recommendations were developed and endorsed by Brazilian Society of Rheumatology and are intended to provide an evidence-based framework to guide health care professionals diagnosing and treating lupus nephritis as well as the development of public and supplementary health policies in Brazil to promote early diagnosis, treatment and damage prevention in SLE patients with lupus nephritis.

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Edgard Torres dos Reis-Neto and Luciana Parente Costa Seguro are first authors and contributed equally to this work.

Authors and Affiliations

Division of Rheumatology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM/Unifesp), Otonis Street, 863, 2 Floor, Vila Clementino, São Paulo, SP, 04025-002, Brazil

Edgard Torres dos Reis-Neto, Emília Inoue Sato & Antonio Silaide de Araujo Junior

Division of Rheumatology, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

Luciana Parente Costa Seguro, Eduardo Ferreira Borba, Eloisa Bonfá & Emily Figueiredo Neves Yuki

Department of Rheumatology, Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil

Evandro Mendes Klumb & Francinne Machado Ribeiro

Division of Rheumatology, Department of Orthopedics, Rheumatology and Traumatology, Universidade Estadual de Campinas (Unicamp), Campinas, Brazil

Lilian Tereza Lavras Costallat & Simone Appenzeller

Division of Rheumatology, Universidade Federal do Ceará (UFC), Fortaleza, Brazil

Marta Maria das Chagas Medeiros

Division of Rheumatology, Hospital do Servidor Público Estadual de São Paulo - Instituto de Assistência Médica ao Servidor Público Estadual de São Paulo, São Paulo, Brazil

Nafice Costa Araújo

Division of Rheumatology, Hospital das Clínicas da Universidade Federal de Goiás, Goiânia, Brazil

Ana Carolina de Oliveira e Silva Montandon

Division of Rheumatology, Universidade Estadual de Ciências da Saúde de Alagoas, Maceió, Brazil

Roberto Cordeiro de Andrade Teixeira

Division of Rheumatology, Faculdade de Medicina da Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil

Rosa Weiss Telles & Debora Cerqueira Calderaro

Division of Rheumatology, Department of Internal Medicine, Universidade Federal da Paraíba (UFPB), João Pessoa, Brazil

Danielle Christinne Soares do Egypto

Division of Rheumatology, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil

Andrese Aline Gasparin & Odirlei Andre Monticielo

Division of Rheumatology, Santa Casa de Misericórdia de Belo Horizonte, Belo Horizonte, Brazil

Cláudia Lopes Santoro Neiva

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Contributions

*ETRN and LPCS are first authors and contributed equally to this work. Conceptualization of this work: ETRN, LPCS, EIS, EFB, EMK, LTLC, MMCM, NCA, SA, ACOSM, EFNY, RCAT, RWT, DCSE, FMR, AAG, ASAJ, CLSN, DCC, OAM. Definition of the guidelines’ scope, generation of PICO questions, voting, and elaboration of recommendations: ETRN, LPCS, EIS, EFB, EMK, LTLC, MMCM, NCA, SA, ACOSM, EFNY, RCAT, RWT, DCSE, FMR, AAG, ASAJ, CLSN, DCC, OAM. Methodology including systematic literature search, formal analysis of the literature, and grading of the evidence quality: ETRN, LPCS, EIS, EFB, EMK, LTLC, MMCM, NCA, SA, ACOSM, EFNY, RCAT, RWT, DCSE, FMR, AAG, ASAJ, CLSN, DCC, OAM. Initial draft manuscript: ETRN, LPCS. Review and editing of the manuscript: ETRN, LPCS, EIS, EFB, EMK, LTLC, MMCM, EB, NCA, SA, ACOSM, EFNY, RCAT, RWT, DCSE, FMR, AAG, ASAJ, CLSN, DCC, OAM. All authors were involved in the production of the recommendations, and have reviewed, discussed, and approved the final manuscript.

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Correspondence to Edgard Torres dos Reis-Neto .

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Ethics approval and consent to participate, consent for publication, competing interests.

The authors declare that the research was carried out in the absence of any commercial or financial relationship that could be interpreted as a potential conflict of interest. Several authors of these guidelines, including voting members, have interacted with the pharmaceutical industry including the manufacturers of some of the drugs mentioned in these recommendations. However, none of the authors received any support or fee directly or indirectly related to or influencing the development of these guidelines. ETRN received speaker fees and/or consultancies from AstraZeneca, GSK and Novartis and participate in clinical research from Abbvie, BMS and Novartis. LPCS received speaker and research fees from AstraZeneca and GSK and participate in clinical research from Abbvie, AstraZeneca, BMS, GSK and Novartis. EIS declares no competing interests. EFB declares no competing interests. EMK received speaker fees and/or consultancies and/or advisory boards from AstraZeneca and GSK. LTLC declares no competing interests. MMCM declares no competing interests. NCA received speaker fees, advisory boards and research fee from AstraZeneca and GSK and speaker fees from Organon. SA received speaker fees from AstraZeneca and GSK; ISS from GSK. ACOSM received speaker fees from AstraZeneca and GSK. EFNY received speaker fees from AstraZeneca. RCAT declares no competing interests. RWT declares no competing interests. DCSE received speaker fees and/or consultancies from Abbvie, AstraZeneca, Janssen and GSK. FMR received speaker fees/advisory boards from GSK and AstraZeneca. AAG declares no competing interests. ASAJ received speaker fees from GSK and AstraZeneca. CLSN received speaker fees from AstraZeneca and GSK, advisory boards from AstraZeneca and participate in clinical research from Abbvie, AstraZeneca, BMS, GSK, Lilly, Merck, Novartis, Pfizer, Roche and UCB. DCC received speaker and research fees from AstraZeneca and GSK and participate in clinical research from BMS, Novartis and Roche. OAM received speaker fees and/or consultancies and/or advisory boards from Abbvie, Astrazeneca, BMS, Celltrion, GSK, Janssen-Cilag, Novartis-Sandoz and UCB.

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Reis-Neto, E., Seguro, L., Sato, E. et al. II Brazilian Society of Rheumatology consensus for lupus nephritis diagnosis and treatment. Adv Rheumatol 64 , 48 (2024). https://doi.org/10.1186/s42358-024-00386-8

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Clustering the Research at the Intersection of Industry 4.0 Technologies, Environmental Sustainability and Circular Economy: Evidence from Literature and Future Research Directions

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Materials and Method

Literature Search, Identification, Screening, and Inclusion

Descriptive, Bibliometric, and Thematic Analyses

Research Performance Assessment: Descriptive Results

Science Mapping Assessment: Cluster Analysis

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Cluster 2: General Linkages Between Circular Economy and Industry 4.0 Topics

Cluster 3: Industry 4.0 and Big Data Analytics for Supply Chain Circularity and Sustainability

Cluster 4: Additive Manufacturing for Circularity and Sustainability

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