Clinical Profile and Outcome of Primary Membranous Nephropathy

Background: Primary membranous nephropathy (MN) is a major cause of nephrotic syndrome in adults, characterized by immune complex formation on the outer side of the glomerular basement membrane. Primary MN accounts for 80% of the cases and 20% cases are associated with a secondary etiology. While immunosuppressive therapy has improved patient outcomes in MN, the clinical profile and treatment outcomes of MN in our patient population have not been previously studied. Methods: This two-year retrospective and prospective observational study, approved by the Institutional Ethics Committee, was conducted at the Department of Nephrology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, India. The primary objective was to investigate the clinicopathological profile and outcomes of primary MN patients. We included consenting patients aged ≥ 18 years with primary MN and excluded those with end-stage kidney disease, pregnancy, or secondary MN. Detailed history, physical examination, laboratory investigations (including 24-hour urinary protein, kidney and liver function tests, and anti-PLA2R antibody levels), and screening for secondary etiologies were performed. Renal biopsy tissues were examined using light microscopy, immunofluorescence, immunohistochemistry for PLA2R, THSD7A, NELL-1, EXT1, EXT2, and electron microscopy. Patients were risk-stratified based on proteinuria, kidney function, and serum anti-PLA2R antibody levels. Remission, relapse, and resistant disease were defined by specific proteinuria and albumin criteria Results: Of 46 patients, 60.9% were female, with a mean age of 43.8 ± 13.7 years. The mean proteinuria was 5.8 ± 3.2 g/day, mean serum albumin was 2.5 ± 0.39 g/dL, and mean eGFR was 99.8 ± 26.6 mL/min/1.73 ² . Edema was the most common symptom (100%), and hypertension was the most frequent comorbidity (37%). Serum anti-PLA2R antibodies were positive in 39.1% of patients. On immunohistochemistry, 58.7% were tissue PLA2R positive and 17.4% were NELL-1 positive. At baseline, 71.1% of patients were in the high-risk category. Initial non-immunosuppressive supportive care was given to 84.8% of patients, with 23.08% achieving remission. Among those receiving immunosuppressive therapy, 72.2% on modified Ponticelli regimen and 85.7% on other regimens achieved remission at 6 months (p=0.432). At 12 months, 82.9% of patients on immunosuppressive therapy achieved remission. Both modified Ponticelli and other immunosuppressive regimens significantly improved proteinuria and serum albumin at 12 months (p<0.0001). Conclusion: PLA2R associated MN was the most common form of MN, followed by NELL-1. Primary MN prevalence was highest in the fifth and sixth decades of life, with a slight female preponderance observed in this study. Most patients presented in the high-risk group. Immunosuppression led to complete remission in over 80% of patients, with no significant difference in remission rates between different immunosuppressive agents. This study provides initial insights into MN in the local patient population, despite its limitations of being a single-center observational study with a relatively small sample size and short follow-up.