Focal Segmental Glomerulosclerosis Recurrence Post Renal Transplant: A Narrative Review

Focal segmental glomerulosclerosis (FSGS) is a leading cause of nephrotic syndrome and progression to end-stage kidney disease (ESKD). It remains one of the most consequential glomerular diseases in kidney transplantation because of its risk of recurrence in the allograft. Rather than a single disease, FSGS is a histopathological pattern of podocyte injury arising from primary, genetic, and secondary causes. Recurrent FSGS (rFSGS) is predominantly a feature of primary disease, affecting approximately 30–60% of recipients, often within the first weeks after transplantation, and is associated with approximately a fivefold increase in graft loss and markedly reduced five-year graft survival. The circulating-factor hypothesis remains the most accepted pathogenic model, supported by rapid post-transplant recurrence, response to plasma exchange, and resolution following re-transplantation of affected allografts into unaffected recipients. Candidate mediators—including suPAR, anti-nephrin antibodies, and cardiotrophin-like cytokine factor-1—have been proposed, but none have been validated as a reliable biomarker. Pre-transplant stratification requires identification of the native phenotype, exclusion of secondary causes, and genetic testing in selected cases. Management is largely empirical: plasma exchange combined with rituximab is the mainstay of disease-directed therapy, supplemented by maximal RAAS inhibition, immunosuppression, and supportive care. Emerging therapies—daratumumab, sparsentan, and SGLT2 inhibitors—offer promise but require further study. Prognosis depends on the therapeutic response, with complete remission restoring graft survival to near-baseline levels. Re-transplantation remains feasible but demands individualised counselling and consideration of pre- or peri-operative prophylaxis in the highest-risk recipients.