Introduction:
Primary membranous nephropathy (PMN) is a common cause for nephrotic syndrome in adults. With discovery of newer antigens in pathogenesis of PMN, our understanding of the disease has advanced. Nerve epidermal growth factor-like 1 (Nell-1) is a recently discovered target antigen in PMN. Here, we describe our experience with Nell-1 positive PMN.
Methods:
In this analysis, we included the PMN patients who had been evaluated for Nell-1 antigen in kidney biopsy. Patients who reported use of fairness creams or consumption of alternative medicines were evaluated for heavy metal toxicity. Data was analyzed with descriptive statistics.
Results:
Between January 2017 and September 2024, a total of 188 membranous nephropathy were diagnosed on biopsy, of which 152 (85.4%) were PMN. Among them, NELL-1 antigen was assessed in 23 (15.1%) and 12 (7.9%) were tested positive for NELL-1 antigen. Median age of NELL-1 positive patients was 42 years and 8 (66.7%) were females. Potential history for heavy metal exposure was present in 7 (58.3%) patients of which the use of fairness cream (n=5, 41.7%) was most common. The heavy metals were assessed in 7 (58.3%) cases of which toxic blood levels of mercury and lead were identified in 4 (33.3%) and 1 (8.3%), respectively. The median urine protein creatinine ratio at baseline was 3.45 g/g and median serum creatinine was 0.74 mg/dl. Among the 12 cases, 10 (83.3%) cases have received some treatment and are under follow-up and two (16.7%) have been recently diagnosed. Four patients with mercury toxicity were treated with D-penicillamine and three (30%) achieved complete remission (CR). Three (30%), two (20%) and one (10%) achieved CR with conservative therapy, rituximab and modified Ponticelli regimen, respectively. One (10%) was resistant to tacrolimus regimen.
Conclusions:
NELL-1 associated PMN is being increasingly recognized. Exposure to mercury through fairness creams is a common predisposing factor in its etiology. Chelating agent such as D-penicillamine can prove effective in achieving remission in PMN related to mercury toxicity. Besides chelation, immunosuppression may be needed to achieve remission. Making general public aware about the adverse effects of unregulatred fairness creams or alternative medicines is necessary to reduce the risk of NELL-1 associated PMN.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.