Circulating Nephrin Antibodies and Post-Transplant Recurrence of Diffuse Podocytopathies: A Systematic Review

Recurrence of diffuse podocytopathy (DP), primarily focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD), after kidney transplantation threatens allograft survival. Circulating nephrin autoantibodies have been linked to disease activity, but post-transplant evidence remains limited. We performed a systematic review with patient-level data extraction including kidney transplant recipients with DP as their native kidney disease from studies reporting serum nephrin antibody testing and post-transplant outcomes. Four studies including 63 recipients (23 pediatric, 40 adult) with DP were included, comprising 53 FSGS, 8 MCD, and 2 steroid-resistant nephrotic syndrome cases. Nephrin antibodies were detected in 22 of 62 recipients (36%) before or within 1 day after transplantation. Recurrence occurred in 34 of 63 recipients (54%), including 20 of 22 (91%) antibody-positive patients. Antibody positivity was strongly associated with recurrence (OR 20.8; 95% CI, 4.2–102.6; P<0.001), with sensitivity of 61%, specificity of 93%, positive predictive value of 91%, and negative predictive value of 68%. Antibody titers correlated with disease activity and declined with remission. Nephrin autoantibodies are associated with post-transplant recurrence of DP and may inform pre-transplant risk stratification and post-transplant monitoring. Standardized assays and larger validation studies are needed.