A Clinicopathological Analysis of Membranous Nephropathy and Its Correlation With the Immunohistochemical Expression of Phospholipase A2 Receptor (PLA2R) in Renal Biopsies in a Tertiary Care Center.

Background  Membranous nephropathy (MN) is the second most common adult-onset nephrotic syndrome worldwide. Traditionally, these were classified as primary and secondary, with primary causes showing higher positivity for various antigens, including M-type phospholipase A2 receptor (PLA2R), a key antigen located in the podocyte against which antibodies are directed. Aim The aim of this study is to analyze the cases diagnosed as MN with clinicopathological parameters and PLA2R positivity by immunohistochemistry in renal biopsies. Methods A retrospective observational study of 65 cases of MN diagnosed in renal biopsies by light microscopy and confirmed by ancillary studies from the Department of Pathology, Sri Ramachandra Medical College and Research Institute over a period of three years (2021-2023). The demographic profile and patient details were obtained from the hospital information system and archival case files. The description of categorical variables was expressed as frequency and percentage. The Chi-squared test and Fisher's exact test were employed to compare the distribution of qualitative variables between the groups. Results This case study includes 65 membranous nephropathy cases, of which 47.7% were diagnosed as primary MN and 52.3% as secondary MN. Of these, serum antinuclear antibody (ANA) positivity was seen in 80.6% of cases of primary MN and 58.8% of cases of secondary MN. Elevated serum C3/C4 levels were noted in 51.6% of primary MN and 47.1% of secondary MN (Ref. C3 = 90-180mg/dl; C4 = 10-40mg/dl). Immunofluorescence for IgG showed a nonspecific association between primary and secondary MN. Immunohistochemistry (IHC) for PLA2R showed positivity in 72.3% of primary MN cases and 27.7% of secondary MN cases. The Chi-squared test and Fisher's exact test showed statistical significance for these parameters. Conclusion This study signifies that primary MN is more frequently associated with positive immunohistochemical expression of PLA2R. These findings help in characterizing these cases as antigen-specific and have helped in the ongoing validation of PLA2R IHC as a diagnostic marker, which aids in monitoring the disease progression, remission, and recurrence. Despite the availability of various modalities for estimating the levels of anti-PLA2R, diagnostic challenges persist. Hence, most renal laboratories continue to adopt renal biopsy staining for IHC PLA2R to identify and monitor the disease progression.