Immunoadsorption for Recurrent Primary Focal Segmental Glomerulosclerosis on Kidney Allografts: A Single-Center Experience and Literature Review

Abstract

Introduction: Primary focal and segmental glomerulosclerosis (FSGS) frequently reoccurs on kidney transplants and may lead to premature allograft loss. There are no guidelines for treating FSGS recurrence on allografts; treatment is based on apheresis (plasma exchange plasmapheresis [PP], semi-specific immunoadsorption [IA] with reusable columns) plus rituximab. Objective: We aimed to assess the efficacy of IA to treat recurrent FSGS. Methods: We report on 7 patients with recurrent FSGS on kidney allograft (proteinuria ≥3 g/g of urinary creatinine or ≥3 g/day); they all received IA. Our primary objective was to reduce proteinuria by > 50%. Patients' mean age was 45 ± 10 years. Postoperative immunosuppression relied on steroids, mycophenolate mofetil, ta-crolimus, with an induction therapy of basiliximab or antithymocyte globulins. Prophylaxis to prevent FSGS recurrence was either rituximab alone (n = 3), rituximab plus either PP or IA (n = 3), or no treatment (n = 1). Mean follow-up was 20 ± 13 months. There was a median of 72 (14-101) IA sessions per patient, that is, a mean of 14 ± 1 sessions per IA column. Results: At 12 months after starting IA, all patients had partial (n = 6) or complete (n = 1) remission, and allograft survival was 100%. The mean reduction in proteinuria within an IA session was 45 ± 15%. At last follow-up, 2 patients are in remission without IA, 3 patients are in partial remission that is IA dependent, and 2 patients lost their allograft due to FSGS recurrence. The most frequent adverse event was cytomegalovirus reactivation (n = 13), which subsided after valganciclovir therapy. Conclusions: We show that recurrence of FSGS can be controlled long term with IA plus rituximab. However, some patients remained dependent on IA.

Therapeutic Options for Recurrence of Primary Focal Segmental Glomerulonephritis (FSGS) in the Renal Allograft: Single-Center Experience

“…Furthermore, since 2000, rituximab has been widely used in FSGS recurrence as adjuvant to plasmapheresis. Rituximab depletes B lymphocytes and also enhances regulatory T cell activity; T cell malfunction is believed to play a major role in pathogenesis of proteinuria [17,41,42]. Moreover, there is evidence of non-immunological actions since rituximab directly modulates podocyte function by preventing the disruption and remodeling of actin cytoskeleton [42].…”

“…Rituximab depletes B lymphocytes and also enhances regulatory T cell activity; T cell malfunction is believed to play a major role in pathogenesis of proteinuria [17,41,42]. Moreover, there is evidence of non-immunological actions since rituximab directly modulates podocyte function by preventing the disruption and remodeling of actin cytoskeleton [42]. An overall response rate of 58 to 79% with the use of rituximab has been reported in such patients [22,[41][42][43].…”

“…Moreover, there is evidence of non-immunological actions since rituximab directly modulates podocyte function by preventing the disruption and remodeling of actin cytoskeleton [42]. An overall response rate of 58 to 79% with the use of rituximab has been reported in such patients [22,[41][42][43]. Although different treatment modalities have been used and it is not always clear which one contributed most to remission, it is probable that the combination of plasmapheresis and rituximab is currently the most promising regimen [3,4,20].…”

Kidney Transplantation for Focal Segmental Glomerulosclerosis: Can We Prevent Its Recurrence? Personal Experience and Literature Review

“…This factor has been suggested by several observations, including the development of proteinuria in rats after injection of proteins eluted from an immunoadsorption (IA) column used by FSGS-treated patients [ 27 ]. This was also suggested by: (i) the disappearance of nephrotic syndrome after transplantation of a kidney from an FSGS patient into a non-FSGS kidney recipient [ 7 , 28 , 29 ]; (ii) the occurrence of a nephrotic syndrome in a newborn of an FSGS mother [ 30 ]; and (iii) the control of nephrotic syndrome with apheresis [ 31 ].…”

Therapeutic Approach for Recurrent Focal Segmental Glomerulosclerosis in Pediatric Renal Transplant Recipients: A Single-Center Experience

“…Limited studies, mainly case reports or case series, have explored the use of immunoadsorption (IA) to treat children with recurrent FSGS after KTx [13, 14]. Among them, a recent French cohort study in pediatric patients reported the efficacy of IA in the management of recurrent FSGS after KTx [9].…”