Is Rituximab Suitable for Patients with Idiopathic Membranous Nephropathy Who are Seronegative for Anti-PLA2R Antibody?

Background: Rituximab (RTX) induces apoptosis in B cells expressing CD20, the efficacy in idiopathic membranous nephropathy (IMN) with seronegative anti-M-type phospholipase A2 receptor (PLA2R) antibody remains unclear. Methods: This multicenter retrospective study enrolled 111 adult patients with biopsy-proven, medium-to-high-risk IMN, whose serum anti-PLA2R antibodies test results were negative (SAb-). All patients received RTX and non-RTX (tacrolimus or cyclophosphamide) therapy. Subsequently, based on glomerular PLA2R antigen results, they divided into glomerular PLA2R positive (GAg+) and glomerular PLA2R negative (GAg-) groups. Compared the remission rate at 15 months between different treatment groups. Results: Of the 111 seronegative patients, 36 were assigned to the RTX group and 75 to the non-RTX group. Among the 76 GAg+ patients, 21 were in the RTX group and 45 in the non-RTX group. Kaplan–Meier analysis demonstrated that the complete remission rate was significantly higher in the non-RTX group than in the RTX groups at 15 months, both in total and SAb-/GAg+ cohort ( P = 0.033, P = 0.034, respectively), but there was no statistically significant difference in overall remission (both P > 0.05). The non-RTX group exhibited significantly lower proteinuria and higher serum albumin levels than the RTX group at 3, 6, and 9 months after treatment. Of the 19 patients who did not achieve remission by the end of follow-up, seven (36.8%) experienced seroconversion. There were no significant differences in adverse events between two groups. Conclusion: For seronegative anti-PLA2R antibodies patients, non-RTX immunosuppressive therapy might offer greater benefit for proteinuria remission compared to RTX in short-term, even if their glomeruli are positive for PLA2R antigen. Keywords: idiopathic membranous nephropathy, anti-PLA2R antibody, proteinuria, remission