Anti-Phospholipase A2 Receptor Antibody Trajectories for Predicting Prognosis in Patients with Phospholipase A2 Receptor-Associated Membranous Nephropathy

INTRODUCTION: Phospholipase A2 receptor (PLA2R) is the major autoantigen in membranous nephropathy (MN); however, the trajectories of anti-PLA2R antibodies and their prognostic implications remain unclear. METHODS: In this retrospective cohort study, we analyzed 1,528 patients with PLA2R-associated MN (2011-2022), each with at least three serial measurements of anti-PLA2R antibody levels. Group-based trajectory modeling was applied to identify distinct longitudinal patterns of antibody change. Associations between antibody trajectories and clinical outcomes were assessed using multivariable Cox proportional hazards and logistic regression models, complemented by Kaplan-Meier analysis. RESULTS: Four distinct serum anti-PLA2R antibody trajectories were identified: rising (5.3%), low-stable (74.8%), declining (14.9%), and high-stable (5.0%). The low-stable group had the lowest rates of renal function decline (15.3%), clinical non-remission (18.8%), and relapse (31.6%). Compared to this group, the risks of renal function decline were significantly higher in the rising (adjusted hazard ratio [aHR] = 3.69; 95% confidence interval [CI]: 2.57-5.30), declining (aHR = 1.66; 95% CI: 1.24-2.21), and high-stable (aHR = 4.18; 95% CI: 2.91-6.00) groups. Similarly, the rates of clinical remission were significantly lower (aHR = 0.38 for rising; aHR = 0.61 for declining; aHR = 0.28 for high-stable), while the odds of relapse were higher (adjusted odds ratio 3.13, 2.35, and 3.17, respectively) in these three groups. These associations remained consistent across sex and age subgroups. CONCLUSION: Serum anti-PLA2R antibody trajectories represent a robust prognosis biomarker in MN, useful for risk stratification and clinical decision-making. Patients with high-stable or rising antibody trajectories require heightened clinical attention due to significantly increased risks of renal function decline, clinical non-remission, and relapse.