Diagnostic accuracy of PLA2R autoantibodies and glomerular staining for the differentiation of idiopathic and secondary membranous nephropathy: an updated meta-analysis

Abstract

The diagnostic performance of M-type phospholipase A2 receptor (PLA2R) autoantibodies and PLA2R glomerular staining in discriminating between idiopathic membranous nephropathy (iMN) and secondary membranous nephropathy (sMN) has not been fully evaluated. We conducted an updated meta-analysis to investigate the accuracy and clinical value of serological anti-PLA2R test and histological PLA2R staining for differentiation iMN from sMN. A total of 19 studies involving 1160 patients were included in this meta-analysis. The overall sensitivity, specificity, diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUROC) of serum anti-PLA2R were 0.68 (95% CI, 0.61-074), 0.97 (95% CI, 0.85-1.00), 73.75 (95% CI, 12.56-432.96) and 0.82 (95% CI, 0.78-0.85), respectively, with substantial heterogeneity (I(2) = 86.42%). Subgroup analyses revealed the study design, publication type, study origin, assay method might account for the heterogeneity. Additionally, the overall sensitivity, specificity, DOR and AUROC of glomerular PLA2R staining were 0.78 (95% CI, 0.72-0.83), 0.91 (95% CI, 0.75-0.97), 34.70 (95% CI, 9.93-121.30) and 0.84 (95% CI, 0.81-0.87), respectively, without heterogeneity (I(2) = 0%). Serological anti-PLA2R testing has diagnostic value, but it must be interpreted in context with patient clinical characteristics and histological PLA2R staining in seronegative patients is recommended.

Figure 1. Flow chart of study selection.

Some studies were excluded for more than one reason. *Did not investigate the diagnostic accuracy of PLA2R as a marker for iMN.

Figure 2. Methodological quality graph.

Reviewer judgment of methodological quality of each individual study included in the analysis, according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool.

Figure 3. Forest plot of the pooled sensitivity and specificity of serum anti-PLA2R for differentiation iMN from sMN.

The black squares in the gray squares and the horizontal lines represent the point estimate and 95% confidence interval (CI), respectively. The dotted line represents the pooled estimate, and the diamond shape represents the 95% CI of the pooled estimate.

Figure 4. Hierarchical summary receiver operating characteristic (HSROC) plot of serum anti-PLA2R for differentiation iMN from sMN.

The summary point represents the summary sensitivity and specificity, the 95% confidence region represents the 95% confidence intervals of the summary sensitivity and specificity and the 95% prediction region represents the 95% confidence interval of sensitivity and specificity of each individual study included in the analysis. The plot also includes study estimates indicating the sensitivity and specificity estimated using the data from each study separately. The size of the marker is scaled according to the total number in each study.

Figure 5. Deek's plots for included studies of serological anti-PLA2R test.

Linear regression of log odds ratios on inverse root of effective sample sizes as a test for funnel plot asymmetry in diagnostic meta-analysis. A non-zero slope coefficient is suggestive of significant small study bias (p < 0.05).