Diagnostic Test Accuracy of Serum Anti-PLA2R Autoantibodies and Glomerular PLA2R Antigen for Diagnosing Idiopathic Membranous Nephropathy: An Updated Meta-Analysis

BACKGROUND: M-type phospholipase A2 receptor (PLA2R) is known as a major antigen on podocytes, which is involved with the pathogenesis of idiopathic membranous nephropathy (iMN). Many studies have shown that serum anti-PLA2R autoantibodies (sPLA2R) are prevalent in patients with iMN but are rarely detected in secondary membranous nephropathy (SMN) or other glomerulonephritis. The anti-PLA2R is considered as a promising serum biomarker in iMN but reports about its diagnostic value are variable and inconsistent. OBJECTIVE: To evaluate the diagnostic test accuracy (DTA) of anti-PLA2R and glomerular PLA2R antigen (gPLA2R) for diagnosing iMN. METHOD: MEDLINE, EMBASE, WEB OF SCIENCE, and COCHRANE LIBRARY were searched from 2009 January to February 2018. Heterogeneity was evaluated by Q test and I(2). Source of heterogeneity was explored by subgroup analysis and meta-regression. Meta-analysis was executed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. RESULTS: Totally, 35 studies were retrieved under the pre-set study eligibility criteria. Twenty-eight studies were included to evaluate the DTA of anti-PLA2R for differentiating iMN from non-iMN. They indicated a pooled sensitivity of 65% (63–67%), specificity of 97% (97–98%), positive likelihood ratio of 15.65 (9.95–24.62), and negative likelihood ratio of 0.37 (0.32–0.42) with a diagnostic OR (sDOR) of 50.41 (31.56 to 80.52) and AUC of 0.9393. No threshold effect was detected. The heterogeneity analysis for sDOR showed that I(2) = 50.3% and Cochran-Q = 54.29, df = 27 (p = 0.0014). Heterogeneity was significant. Meta-regression revealed that sample size might be the potential source of heterogeneity. Subgroup analysis demonstrated that method type and ratio of patients with nephrotic-range proteinuria at baseline might be the source of heterogeneity. Sixteen studies reported the diagnostic value of glomerular PLA2R antigen for differentiating iMN from non-iMN. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, sDOR, and AUC were 79% (76–81%), 90% (88–92%), 8.17 (5.60–11.93), 0.25 (0.19–0.33), 39.37 (22.18–60.13), and 0.9278. Heterogeneity analysis showed that Cochran-Q = 35.36; df = 15 (p = 0.002), and I(2) for sDOR was 57.6%. CONCLUSION: sPLA2R and gPLA2R demonstrated a good diagnostic accuracy in differentiating iMN and non-iMN.