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.

Automated summary

This study found a clear association between baseline anti-PLA2R1 antibody titer and severity of nephrotic syndrome in membranous nephropathy patients, but this association was no longer significant when considering proteinuria and serum creatinine in the analysis. The relevance of a single measurement of anti-PLA2R1 antibodies at baseline as a prognostic biomarker in membranous nephropathy is questioned, suggesting the need for future studies on sequential measurements for disease progression prediction.