A Review and Future Perspective on Renal Outcome Definitions in Lupus Nephritis

Lupus nephritis (LN) remains a leading cause of morbidity and mortality in systemic lupus erythematosus, yet the lack of standardized definitions for renal outcomes hinders effective diagnosis, prognosis, treatment personalization, comparisons across trials, and interpretable trial endpoints. Despite significant advances in biomarker discovery, treatment strategies, and histopathological classification, substantial challenges and controversies persist in defining and assessing renal response to therapy. Following a January 2025 roundtable discussion on the subject of LN outcome definitions, a workgroup was established to address these issues and provide an expert perspective on the future of outcome definitions based on current literature. Here, we examine the current limitations of renal outcome definitions and advocate for change toward improved interpretation and comparison of clinical study data. Key areas, such as limitations of traditional kidney function markers and the need for reliable endpoints reflecting improvements in renal inflammation in trials, are addressed. As an international workgroup of rheumatologists and nephrologists with experience in managing LN, we advocate for a unified approach considering standard per-protocol repeat biopsies for histologic response evaluation, estimated glomerular filtration rate slope, glucocorticoid minimization/withdrawal, and extended follow-up for the evaluation of sustained long-term outcomes. The importance of harmonizing clinical and histologic definitions and the potential of novel biomarkers are highlighted. Herein, we provide a perspective toward uniform definitions of response in LN trials, renal flare/relapse, and refractory disease with improved applicability, especially in the context of advanced immunosuppressives. Thereby, we aim to facilitate meaningful study and advanced treatment of LN, ultimately enhancing patient outcomes and future research.