Anti-PLA2R1 Antibodies as Prognostic Biomarker in Membranous Nephropathy

Introduction: Personalized treatment for patients with membranous nephropathy requires accurate prediction of the disease course at an early stage. In this study, we evaluated the value of baseline anti-phospholipase A2 receptor (PLA2R1) antibody titer as a prognostic biomarker in patients with PLA2R1-associated membranous nephropathy. Methods: In this cohort study, we included 168 patients (118 men, 50 women) referred to our nephrology center between February 1995 and November 2016. Mean age was 52 +/- 13 years. There were 156 patients with new-onset disease and 12 patients with a relapse (n = 10) or recent use of immunosuppressive therapy (n = 2). We measured anti-PLA2R1 titer at baseline and analyzed progression to severe disease (30% increase of serum creatinine or start of immunosuppressive therapy) as a primary study endpoint over 60 months. Results: There was a clear association between anti-PLA2R1 antibody titer and severity of the nephrotic syndrome. In univariate analysis, anti-PLA2R1 antibody titer was also associated with disease progression. However, in Cox proportional hazard models that included proteinuria and serum creatinine, anti-PLA2R1 antibody titer was no longer associated with clinical outcome. Results were similar when limiting the analysis to the patients with new-onset disease. Conclusion: Our study questions the relevance of single measurement of anti-PLA2R1 antibodies at baseline as a prognostic biomarker in membranous nephropathy. Future studies are needed to determine the possible role of sequential measurements of anti-PLA2R1 antibodies as a prognostic biomarker of disease progression.