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

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.