Recurrent Membranous Nephropathy after Kidney Transplantation: Treatment and Long-Term Implications

Background Membranous nephropathy (MN) can recur in kidney allografts leading to graft dysfunction and failure. The aims of these analyses were to assess MN recurrence, clinical and histologic progression, and response to anti-CD20 therapy. Methods Included were 63 kidney allograft recipients with biopsy proven primary MN followed up for 77.0 (39-113) months (median, interquartile range). Disease recurrence was diagnosed by biopsy (protocol or clinical), and follow-up was monitored by laboratory parameters and protocol biopsies. Results Thirty of 63 patients (48%) had histologic recurrence often during the first year. In 53% of the cases, recurrence was diagnosed by protocol biopsy. Recurrence risk was higher in patients with higher proteinuria pretransplant [hazard ratio = 1.869 (95% confidence interval, 1.164-3.001) per gram, P = 0.010] and those with anti-phospholipase A2 receptor antibodies [hazard ratio = 3.761 (1.635-8.652), P = 0.002]. Thirteen patients with recurrence had no clinical progression, and in 2, MN resolved histologically. Seventeen of 63 patients (27%) had progressive proteinuria and were treated with anti-CD20 antibodies, resulting in complete response in 9 (53%), partial response in 5 (29%), and no response in 3 (18%). Posttreatment biopsies were obtained in 15 patients and showed histologic resolution in 6 (40%). Disease recurrence did not correlate with graft survival. However, 5 of 11 (45.4%) graft losses were due to recurrent MN. Death-censored graft survival in MN did not differ from that of 273 control recipients with autosomal dominant polycystic kidney disease. Conclusions Membranous nephropathy recurs in 48% of cases threatening the allograft. Treatment of early but progressive recurrence with anti-CD20 antibodies is quite effective achieving clinical remission and histologic resolution of MN.