Anti-PLA2R antibody levels and clinical risk factors for predicting relapse in primary membranous nephropathy

Objectives To explore the predictive value of anti-phospholipase A2 receptor (PLA2R) antibody levels and clinical risk factors for relapse in patients with primary membranous nephropathy (pMN) who achieved remission after immunosuppressive therapy. Methods This study was a single-center, retrospective, cohort study. Patients with biopsy-proven pMN from Jining No.1 People’s Hospital, who had a follow-up period of at least 12 months, were enrolled. Three landmark time points were evaluated: baseline and 3 and 6 months after treatment initiation. Multivariable Cox regression, receiver operating characteristic curve analysis, and Kaplan–Meier survival analysis were performed. Cox model discrimination and fit were assessed using Harrell’s C-index and the Akaike information criterion (AIC), respectively. Results A total of 154 patients with PLA2R-associated pMN were included in the study. Among the 96 patients (62.34%) who achieved remission (either partial or complete) within 12 months, 17 (17.71%) experienced a relapse; the median time from treatment initiation to relapse was 23 months. The baseline anti-PLA2R antibody level in the relapse group was significantly higher than that in the non-relapse group ( p < 0.001). In the 3-month landmark model, anti-PLA2R antibody seropositivity at 3 months (≥ 14 RU/mL) was independently associated with a higher subsequent risk of relapse (HR 9.44, 95% CI 2.69-33.21; p < 0.001), whereas a greater increase in serum albumin from baseline to 3 months was associated with a lower relapse risk (HR 0.85, 95% CI 0.74-0.98; p = 0.03). The 3-month landmark model demonstrated better model fit and discrimination than the 6-month landmark model, with a lower AIC (123.41 vs. 138.84) and a higher C-index (0.83 vs. 0.66). Conclusion In this exploratory study, anti-PLA2R antibody seropositivity and a blunted increase in serum albumin after 3 months of treatment were identified as potential risk factors for relapse among patients with pMN who achieved remission. Larger-scale studies are warranted for further validation.