Diagnostic Accuracy of Serum Anti-phospholipase A2 Receptor (PLA2R) Antibody Assays for Membranous Nephropathy in Patients With Nephrotic Syndrome: A Systematic Review.

Abstract

Primary membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults, and circulating anti-phospholipase A2 receptor (PLA2R) antibodies have emerged as a key diagnostic biomarker. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we conducted a systematic review of eight studies evaluating serum PLA2R antibody testing against kidney biopsy, with sample sizes ranging from 117 to 670 participants. Extracted data included assay type, cutoff values, sensitivity, specificity, and area under the curve (AUC), where available. Across 2,600+ patients, reported sensitivities ranged from 60% to 80.75%, while specificity was generally ≥90%, and five studies reported AUCs between 0.83 and 0.935, with a weighted mean AUC of 0.877. Lower cutoffs (~2-3 RU/ml) increased sensitivity at the cost of slightly reduced specificity. In contrast, higher cutoffs (>20 RU/ml) improved specificity at the cost of lower sensitivity, and combined ELISA and confirmatory indirect immunofluorescence further increased specificity to 100% but decreased sensitivity. These findings indicate that serum PLA2R antibody testing is a reliable rule-in diagnostic tool for MN, although negative results cannot reliably exclude the disease. Future large-scale prospective studies with standardized cutoffs and complete 2 × 2 contingency data are needed to enable formal meta-analytic pooling and optimize diagnostic thresholds and cutoff selection for clinical practice.