Long-Term Results of Early Plasmapheresis to Prevent Recurrence of FSGS in High-Risk Renal Transplant Recipients

Background: Recurrent focal segmental glomerulosclerosis (FSGS) following transplantation occurs in 30-40% of affected patients and has been ascribed to the presence of a circulating permeability factor (FSPF). Plasmapheresis (PP) can induce remission of proteinuria in recurrent FSGS and may have a role in preventing recurrence if performed preemptively. However, predicting which patients will recur remains problematic. Methods: Clinical parameters (biopsy-proven FSGS, end-stage renal disease within 3 years of diagnosis or advanced azotemia at presentation or prior allograft loss due to recurrent FSGS) were used to identify patients deemed to be at high-risk for recurrence, who subsequently underwent a protocol of 8 PP treatments in the perioperative period. Recurrence rates, outcomes and treatment responses were compared to those individuals diagnosed with FSGS who did not meet criteria for study participation (“low-risk” patients). Results: A total of 707 adult and pediatric kidney transplants were performed during the study period (1999 – 2009) with 46 (6.5%) having some prior diagnosis of FSGS. Of these, 14 (2% of the total) met the clinical criteria for a high risk of disease recurrence and underwent the study protocol. There was a significantly greater risk of developing recurrent FSGS in the high-risk arm with 5/14 (36%) patients experiencing biopsy-proven recurrent disease compared to none detected in the low-risk group. All patients with recurrence were treated with additional courses of PP. Two patients experienced partial remissions (proteinuria < 2 g/day) and one a complete remission. Death-censored graft survival was similar between the two groups although survival in the low-risk arm was lower than expected due to an excess of patient deaths. Graft function as estimated by serum creatinine was excellent and comparable in both study arms (1.4 mg/dl, low-risk vs 1.5 mg/dl, high-risk). Conclusion: The results indicate that patients at high risk for FSGS recurrence can be identified based on clinical parameters. Furthermore, PP may play a role in decreasing the incidence of recurrent FSGS in high-risk patients, although definitive conclusions regarding optimal management in this patient population can only be drawn from a large, randomized and controlled study.