# 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.

## Key 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.