Neural Epidermal Growth Factor-Like 1 (NELL-1)-Associated Membranous Nephropathy: A Clinical and Outcome-Based Study From a Tertiary Care Center

TL;DR

This study examines NELL-1-associated membranous nephropathy, finding that many patients achieve remission with treatment or removal of underlying causes like mercury exposure or cancer.

Contribution

The study provides new clinical insights into the heterogeneous nature and treatment outcomes of NELL-1-associated membranous nephropathy.

Findings

18.5% of membranous nephropathy cases were associated with NELL-1, with half being idiopathic.

Proteinuria and serum albumin significantly improved over a 23-month follow-up period.

66.7% of patients achieved complete remission, highlighting the effectiveness of supportive care and immunosuppression.

Abstract

Introduction: Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults, with neural epidermal growth factor-like 1 (NELL-1) identified as a novel target antigen in a subset of cases. This study aimed to evaluate the clinical profile, secondary associations, treatment, and outcomes of NELL-1-associated MN in a single-center cohort.

Methods: We conducted a retrospective observational study at a tertiary care center, reviewing all patients diagnosed with MN between January 2022 and April 2024. Patients with NELL-1-positive MN on renal biopsy immunohistochemistry were included. Clinical data, secondary causes (autoimmune diseases, toxic exposures, malignancies), treatments, and outcomes (remission status, proteinuria, serum albumin) were analyzed.

Results: Among 65 MN patients, 12 (18.5%) had NELL-1-associated MN (66.7% female; median age 34 years). Secondary associations included exposure to mercury-containing skin-whitening cream in three patients (25%), malignancy in two (16.7%), and psoriasis in one (8.3%), while six patients (50%) had primary (idiopathic) NELL-1-associated MN. Initial therapy was conservative (renin-angiotensin system blockade and supportive care) in most; seven patients ultimately required immunosuppressive therapy due to persistent nephrotic syndrome or secondary causes. Over a mean follow-up of 22.9 ± 10.6 months, proteinuria significantly decreased (from 5.7 ± 4.3 g/day to 0.5 ± 0.7 g/day; p = 0.002), and serum albumin improved (2.7 ± 1.0 g/dL to 4.0 ± 0.5 g/dL; p = 0.006). By the last follow-up, eight patients (66.7%) achieved complete remission and three (25%) partial remission; one patient died during follow-up.

Conclusion: NELL-1-associated MN encompasses a heterogeneous spectrum of primary and secondary cases. Identifying inciting factors such as toxic exposures or malignancies is crucial, as withdrawal or treatment of the underlying cause can lead to remission. A majority of patients achieved remission with supportive care and/or immunosuppression, but relapses can occur. Long-term follow-up and patient education are essential. Larger studies are needed to inform optimal management strategies for NELL-1-associated MN.