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.