High plasmapheresis dependency after treatment of recurrent post-transplant focal and segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is a leading cause of end-stage renal disease (ESRD), with recurrence rates of 20–50% within the first year after kidney transplantation. Although plasmapheresis (PP) and rituximab (RTX) have emerged as promising therapies, long-term outcomes remain unpredictable. This study aims to evaluate the efficacy of combined PP and RTX in achieving remission of nephrotic proteinuria and preserving graft function in FSGS recurrence. This retrospective single-center study included 20 kidney transplant patients with confirmed FSGS recurrence between 2017 and 2022. Treatment consisted of an initial course of five plasmapheresis sessions on alternate days, followed by two intravenous rituximab doses (375 mg/m²) administered two weeks apart, with subsequent plasmapheresis resumed and tapered according to clinical response. Primary endpoints were the rate of complete or partial proteinuria remission and graft survival. Secondary outcomes included adverse events (AEs) and the need for further PP/RTX treatments. Of the 20 patients, 65% (n = 13) achieved remission (4 complete and 9 partial remissions), with 23.1% showing sustained remission for at least 24 months and 53.9% (n = 7/13) became PP dependent. Proteinuria was significantly reduced, and there was a marked improvement in estimated glomerular filtration rate (eGFR) in the complete remission group. There were 5 (25%) graft losses, none of them in patients who achieved remission. Early initiation of PP/RTX induced proteinuria remission in a substantial proportion of patients with recurrent FSGS, albeit with a high rate of PP dependence. Despite relevant infectious adverse events, no graft loss or deaths occurred among patients achieving remission. What was known FSGS recurrence after kidney transplantation presents significant challenges, with recurrence rates between 20-50%. PP and RTX have shown promise in managing this condition, but long-term outcomes and the efficacy of combined treatment remain uncertain. This study adds This study demonstrate that combined PP and RTX therapy can induce remission in a substantial proportion of patients with recurrent FSGS; however, sustained remission was achieved in only a minority and frequently required ongoing PP. Potential impact The findings suggest that early intervention with PP and RTX may improve short- and mid-term outcomes in FSGS recurrence; however, the high rate of PP dependence highlights the urgent need for more effective and durable therapeutic strategies.