Anti-PLA2R1 Antibodies and Membranous Nephropathy Recurrence after Kidney Transplantation

Introduction Membranous nephropathy can lead to end-stage kidney disease, for which kidney transplantation is the preferred therapy. However, the disease often relapses, which can impact allograft survival. Methods We conducted a prospective multicenter study in France involving 72 patients with membranous nephropathy who were awaiting and then underwent kidney transplantation. Additionally, we established a retrospective validation cohort of 65 patients. The primary objective was to evaluate the prognostic significance of pre-transplant anti-PLA2R1 antibodies on the recurrence of membranous nephropathy. The study also assessed the incidence rate, time to onset, and risk factors for recurrence, as well as allograft outcome. Results The prospective cohort showed a 26% cumulative incidence of membranous nephropathy recurrence after a median follow-up of 23.5 months. This was confirmed by a 28% cumulative incidence after a median follow-up of 67 months in the retrospective cohort. A strong association was found between the presence of anti-PLA2R1 antibodies prior to transplantation and the risk of disease recurrence (RR=5.9 [CI 95%, 2.3;15.7], p<0.0001). These results were confirmed in the retrospective cohort. Monitoring of anti-PLA2R1 antibodies in the immediate post-transplant period is of limited value, as recurrence occurred early in the first six months (median delay of 5 [3;14] months) after transplantation despite decreasing antibody levels. Conclusion The presence of anti-PLA2R1 antibodies prior to transplantation was a strong predictor of recurrence of allograft membranous nephropathy. An individualized immunomonitoring and management strategy for kidney transplant candidates with anti-PLA2R1-associated membranous nephropathy should be considered.