Rituximab does not Prevent Focal and Segmental Glomerulosclerosis Recurrence after Renal Transplantation in Patients at Risk

Abstract

SENTRA-GLOSEN. Introduction Recurrence of focal and segmental glomerulosclerosis (FSGS) after renal transplantation is a characteristic complication of the disease that occurs in one third of the cases and has an important detrimental influence on graft survival. Different characteristics have been proposed as risk factors for recurrent disease although there is no general agreement on their importance and significance. Some studies have suggested that rituximab, administered at the time of transplantation, may be effective in preventing recurrence, but such efficacy has not been corroborated. Materials and Methods We perform a multicenter retrospective cohort study including 93 kidney transplants between years 2000 and 2014 in 87 patients [6 patients received a second transplant] with biopsy-proven FSGS as the underlying primary disease; patients with genetic or secondary causes were excluded. The aims of the study are to identify those factors that predict proteinuria recurrence and to analyze the efficacy of rituximab as preventive treatment in patients at risk. We also evaluate remission after recurrence treatment and the impact of recurrence on the graft survival. Results Fifteen patients (16.1%) presented a FSGS recurrence. When the analysis was restricted to those patients presenting with nephrotic syndrome at baseline, the incidence of recurrence increased to 44.1%. A younger age at diagnosis, a lower serum albumin and higher amount of proteinuria at baseline, more frequent immunosuppressive treatments at baseline, a higher number of relapses in previous transplants and a lower age at the time of transplantation were associated with the risk of recurrence. By multivariate analysis, the only risk factor for FSGS recurrence was the value of serum albumin at baseline. RTX (1g at induction and 1g two weeks after transplantation) was used as a potential prophylactic treatment in 12 of the 34 patients considered at risk for FSGS recurrence (hypoalbuminemia and nephrotic proteinuria at baseline). Clinical and analytical characteristics, both at baseline and at transplantation, were similar in both groups. No differences were found in the number of recurrences: 6/12 (50%) among RXT-treated patients and 9/22 (40.9%) versus non-treated patients (p = 0.610). Proteinuria remission after different treatments, most of them including plasmapheresis, was observed in 71.4% of patients. The addition of RTX to plasmapheresis did not increase efficacy. FSGS recurrence had a remarkable impact on graft survival, with 53% functioning grafts at the end of follow-up among patients who had suffered recurrence versus 88,5% in those who did not (p = 0.004); graft survival of FSGS recurrent patients achieving proteinuria remission after treatment was similar to that of patients without recurrence. Discussion In conclusion, the presence of hypoalbuminemia at the onset of the disease is the main predicting factor for FSGS recurrence. Rituximab does not prevent FSGS recurrence in patients at risk.