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 (I2 = 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 (I2 = 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.

The Genetic and Environmental Factors of Primary Membranous Nephropathy: An Overview from China

“…Circulating PLA2R antibodies seem to be specific for pMN [32-34]; however, they can also occur in secondary MN, especially the hepatitis B virus-related MN common in China [35]. The prevalence of positive antibodies varies between different diagnostic centers, from the highest prevalence of 82% [36] to the lower prevalences of 68% [37], 59% [38], and 69% [39], respectively, in China.…”

The clinicopathological features of patients with membranous nephropathy

“…4 sMN could be induced by various conditions, such as malignancies (breast, ovarian, lung, and stomach cancers, and lymphoproliferative disorders), infections (human immunodeficiency virus, malaria, hepatitis B and C viruses), some systemic autoimmune diseases (rheumatoid arthritis and lupus), and the consumption of drugs and toxins. 5,6 MN is characterized by non-selective proteinuria, with the nephrotic range of more than 3.5 g/day.…”

Anti-Phospholipase A2 Receptor Antibodies as Diagnostic Modality in Primary Idiopathic Membranous Nephropathy

“…This study found an overall sensitivity, specificity, diagnostic odds ratio and ROC-AUC of serum anti-PLA2R to be 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%) between the studies . [20] Another similar study for PLA2R displayed 99% specificity and 78% sensitivity for the diagnosis of primary MN with tissue staining and serology distinguishing most cases of primary MN from secondary . [21] Larsen et al in his series of 85 primary MN and 80 secondary MN found sensitivity of 75% (95% CI: 65−84%) and specificity of 83% (95% CI: 72−90%).…”

“…Subgroup analysis by Huanzi Dai et al showed significant discrepancy between different forms of secondary MN with highest diagnostic accuracy when secondary MN was lupus MN. 20 We did not carry out subgroup analysis but all our cases of Lupus Nephritis Class V were negative for PLA2R.It suffices to say that clinical significance of anti-PLA2R1 antibodies in secondary MN with positive PLA2R staining requires wider sampling and screening is necessary for specific subgroups especially in older patients even if serological anti-PLA2R and/or histological PLA2R antigen is positive.…”