Immunohistochemical Glomerular Expression of Phospholipase A2 Receptor in Primary and Secondary Membranous Nephropathy: A Retrospective Study in an Indian Cohort with Clinicopathological Correlations

Abstract

Background: Limited published literature exists on the utility and standardization of anti-phospholipase A2 receptor (anti-PLA2R) immunohistochemistry (IHC) for the diagnosis of primary membranous nephropathy (MN). The study aimed to validate anti-PLA2R IHC for the diagnosis of primary MN and clinicopathological correlations in an Indian cohort. Methods: Subjects included patients with primary and secondary MN diagnosed between January 2012 and August 2014 with an adequate renal biopsy and at least 1 year of clinical follow-up. Anti-PLA2R IHC was performed in all cases with miscellaneous renal lesions as controls. Electron microscopy was performed in selected cases. Sensitivity and specificity of anti-PLA2R IHC to identify primary MN was evaluated. Histopathological analyses of primary and secondary MN were done with clinicopathological correlations including serum creatinine, eGFR, chronic kidney disease stage, 24-h urine protein, serum cholesterol, serum albumin, and hypertension at presentation and follow-up, using the Kruskal-Wallis test and Spearman rank correlation. A p value of ≤0.05 was considered statistically significant. Results: In 153 MN patients (99 primary, 54 secondary) and 37 miscellaneous controls, anti-PLA2R IHC differentiated primary from secondary MN with a sensitivity of 70.2% and a specificity of 96.6%. Secondary MN had increased mesangial matrix expansion compared to primary MN (p = 0.001). Severe nephrotic syndrome, impaired renal function, and hypertension were all more common in primary than in secondary MN. Conclusion: Anti-PLA2R IHC is a specific marker to distinguish primary MN from secondary MN.