A Rare Case of Neural Epidermal Growth Factor-Like 1 Protein (NELL-1) Antigen-Associated Membranous Nephropathy

Abstract

Membranous nephropathy (MN) is an autoimmune disease resulting in nephrotic syndrome. Neural epidermal growth factor-like 1 protein (NELL-1) has been shown to cause a rare form of MN that is more likely to be associated with malignancy. We present a case of a 73-year-old female who was found to have a NELL-1-associated segmental MN. She presented complaining of generalized weakness, chills, and poor appetite, worsening over a one-week duration. Her kidney functions were noted to be markedly deranged, with a computed tomography scan of the abdomen showing evidence of chronic kidney disease. Further testing confirmed heavy proteinuria, although the etiology was still uncertain. A kidney biopsy revealed granular subepithelial immunoglobulin G deposits with subsequent immunohistochemical staining for NELL-1 antigen being positive. She improved with supportive care over the next few days. Despite an extensive workup, no underlying malignancy was found. NELL-1 is a rare yet recognized antigen target for the development of MN. Up to a third of patients with NELL-1-associated MN have associated cancer, thus requiring evaluation for underlying malignancy in this cohort.

A Case of NELL-1-Positive Membranous Nephropathy With Acute Kidney Injury Due to Bilateral Renal Vein Thrombosis

“…In 2019, a study of 210 PLA2R-negative MN biopsies found 16% positivity for NELL-1. This exceeded twice the number of THSD7A-positive cases (15 out of 154 PLA2R-negative cases, 10%) [ 9 ]. In 2021, Caza et al [ 10 ] found that 3.8% of MN cases negative for THSD7A and PLA2R were NELL-1 positive.…”