Clinical profile and outcome of primary membranous nephropathy: A tertiary care center experience from North India

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. AIM 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. METHODS This study approved by the institutional ethics committee, was conducted at the Department of Nephrology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, India. Detailed history, physical examination, laboratory investigations including 24-hour urinary protein, kidney and liver function tests, and anti-phospholipase A2 receptor (PLA2R) antibody levels, and screening for secondary etiologies were performed. Renal biopsy tissues were examined using light microscopy, immunofluorescence, immunohistochemistry for PLA2R, thrombospondin type 1 domain-containing 7A, neural epidermal growth factor-like 1 (NELL-1), exostosin 1, exostosin 2, 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 estimated glomerular filtration rate was 99.8 ± 26.6 mL/minute/1.73 m2. 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 belonged to 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.