Lupus nephritis trials network (LNTN) repeat kidney biopsy-based definitions of treatment response: A systematic literature review-based proposal

Ioannis Parodis; Nursen Cetrez; Leonardo Palazzo; Valeria Alberton; Hans-Joachim Anders; Ingeborg M Bajema; Nathalie Costedoat-Chalumeau; Ana Malvar; Brad H Rovin; Jorge Sanchez-Guerrero; Ming-Hui Zhao; Julia Weinmann-Menke; Maria G Tektonidou; Frédéric A Houssiau

doi:10.1016/j.autrev.2025.103810

Lupus nephritis trials network (LNTN) repeat kidney biopsy-based definitions of treatment response: A systematic literature review-based proposal

Autoimmun Rev. 2025 Apr 1;24(7):103810. doi: 10.1016/j.autrev.2025.103810. Online ahead of print.

Authors

Affiliations

¹ Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine (CMM), Stockholm, Sweden; Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden. Electronic address: ioannis.parodis@ki.se.
² Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine (CMM), Stockholm, Sweden.
³ Pathology Unit, Hospital Fernández, Buenos Aires, Argentina.
⁴ Division of Nephrology, Hospital of the Ludwig Maximilians University Munich, Munich, Germany.
⁵ Department of Pathology and Medical Biology, University of Groningen, University Medical Center, Groningen, the Netherlands.
⁶ Service de médecine interne, Centre de reference maladies autoimmunes et systémiques rares Île de France, APHP, Hopital Cochin, Université de Paris Cité, Centre de Recherche Épidémiologie et Biostatistiques de Sorbonne Paris Cité, Paris, France.
⁷ Nephrology Research Unit, Organización Médica de Investigación, Buenos Aires, Argentina.
⁸ Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH, USA.
⁹ Mount Sinai Hospital and University Health Network, University of Toronto, Canada.
¹⁰ Renal Division, Peking University First Hospital, Beijing, China; Institute of Nephrology, Peking University, Beijing, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.
¹¹ Department of Nephrology, Rheumatology and Kidney Transplantation, Center of Immunotherapy (FZI), Medical Center of the Johannes Gutenberg University, Mainz, Germany.
¹² First Propaedeutic and Internal Medicine Department, Joint Academic Rheumatology Program, National and Kapodistrian University of Athens, Athens, Greece.
¹³ Pôle de Pathologies Rhumatismales Inflammatoires et Systémiques, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium; Service de Rhumatologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

PMID: 40180257
DOI: 10.1016/j.autrev.2025.103810

Abstract

Within the frame of the Lupus Nephritis Trials Network (LNTN), we conducted a systematic literature review (SLR) to propose kidney tissue-based definitions of treatment outcomes in lupus nephritis (LN). Given the limitations of clinical markers like proteinuria in predicting immunological, histological, and long-term outcomes, our work emphasises the importance of repeat kidney biopsies. Such biopsies help identify discordance between clinical and histological response, which has implications for long-term kidney outcomes. The research objectives of this SLR focused on defining repeat biopsy-based treatment response and histological remission, and their associations with long-term outcomes. The SLR reviewed studies published from 2000 to 2022, identifying 20 eligible works. Histological response was commonly defined by changes in the National Institutes of Health (NIH) Activity Index (AI), with response indicated by a decrease of ≥50 % and to ≤3. Remission was most commonly defined as an AI score of 0. These benchmarks were associated with improved long-term renal outcomes, such as reduced flare rates and preserved kidney function. Conversely, NIH AI scores ≥4 and NIH Chronicity Index (CI) scores ≥4 were associated with poor prognosis, highlighting their predictive utility. Consensus definitions were established through expert panel deliberation, setting a foundation for standardising LN treatment evaluation in clinical trials and observational studies. These definitions are not intended for routine clinical decisions but aim to enhance uniformity and comparability in research, especially when repeat kidney biopsies are performed, an approach strongly advocated by our work. Further validation through ongoing initiatives and molecular characterisation efforts will refine these criteria, fostering advances in LN management and patient outcomes.

Keywords: Autoimmunity; Kidney biopsy; Lupus nephritis; Rheumatology; Systemic lupus erythematosus.

Publication types

Review