Prophylactic interventions for focal segmental glomerulosclerosis recurrence after kidney transplantation: a systematic review and network meta-analysis

Background: Primary focal segmental glomerulosclerosis (FSGS) frequently recurs after kidney transplantation and remains a major cause of premature allograft failure. Despite multiple proposed preventive strategies, no standardized approach has been established. This review aimed to systematically evaluate and compare the efficacy and safety of prophylactic interventions for preventing recurrent FSGS following kidney transplantation. Methods: We performed a systematic review and network meta-analysis of randomized and nonrandomized studies including patients with primary FSGS undergoing kidney transplantation. PubMed and Embase were searched through July 2025. Any intervention administered prior to FSGS recurrence-either before or shortly after transplantation-was eligible for inclusion. The primary outcome was posttransplant FSGS recurrence; secondary outcomes included proteinuria, time to recurrence, and treatment-related adverse events. Results: Twenty-five unique studies evaluating six interventions were included in the systematic review. None of the prophylactic strategies significantly reduced recurrence compared with control. The combination of rituximab and plasma exchange yielded lower effect estimates than either intervention alone, but this difference did not reach statistical significance. Evidence for belatacept and bleselumab was limited to single studies; however, their findings warrant further investigation. Adverse events were infrequently reported. Conclusions: Current evidence does not support a definitive prophylactic strategy to prevent recurrent FSGS after kidney transplantation. These findings remain inconclusive, and confirmation of potential benefit-or lack thereof-requires adequately powered randomized trials. Future multicenter studies should standardize recurrence definitions, timing of prophylaxis, and safety reporting.