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

Recurrence of diffuse podocytopathy (DP), primarily focal segmental glomerulosclerosis and minimal change disease, after kidney transplantation threatens allograft survival. Circulating nephrin autoantibodies have been linked to disease activity, but posttransplant 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 posttransplant outcomes. Four studies including 63 recipients (23 pediatric and 40 adult) with DP were included, comprising 53 focal segmental glomerulosclerosis, 8 minimal change disease, and 2 steroid-resistant nephrotic syndrome cases. Nephrin antibodies were detected in 22 of 62 tested recipients (36%), either before transplantation or during posttransplant recurrence, including one patient in whom antibodies were detected 9 years 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 posttransplant recurrence of DP and may inform pretransplant risk stratification and posttransplant monitoring. Standardized assays and larger validation studies are needed.