Sustained remission of NELL-1-positive membranous nephropathy after lung adenocarcinoma resection and during subsequent atezolizumab therapy in a 68-year-old man: a case report

Background: Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults and may occur secondary to malignancy, with lung cancer representing one of the most frequently associated malignancies. Neural epidermal growth factor-like 1 (NELL-1), identified as a target antigen in MN in 2019, has been associated with malignancy, although reported frequencies vary across cohorts. Clinical data regarding the course of NELL-1-positive MN during cancer recurrence and immune checkpoint inhibitors (ICIs) therapy remain limited.

Case Description: A 68-year-old man with no significant past medical history, a 33-pack-year smoking history, and previous occupational concrete dust exposure presented with bilateral lower extremity edema. Laboratory testing revealed nephrotic syndrome [serum albumin: 1.3 g/dL, urine protein-to-creatinine ratio (UPCR): 8.0 g/gCr, serum creatinine: 1.12 mg/dL]. Renal biopsy showed diffuse glomerular basement membrane (GBM) thickening with holes, subepithelial electron-dense deposits, relative immunoglobulin G (IgG) 1 predominance, and strong NELL-1 positivity, establishing NELL-1-positive MN. Subsequent malignancy screening identified a 15-mm pulmonary nodule, which was histopathologically diagnosed as stage IIIA (pT1bN2M0) lung adenocarcinoma following surgical resection. Without corticosteroids or immunosuppressive therapy, proteinuria declined after resection; at 4 months, serum albumin was 2.4 g/dL, UPCR 2.3 g/gCr, and serum creatinine 1.1 mg/dL. Renal parameters subsequently continued to improve, without nephrotic relapse. Eight months after surgery, multiple pulmonary metastases developed, and carboplatin, nab-paclitaxel, and atezolizumab were initiated. Before ICI initiation, renal remission had been established, with serum albumin of 3.6–3.8 g/dL, serum creatinine of approximately 1.1 mg/dL, and negative proteinuria. This remission was maintained throughout approximately 15 months of atezolizumab therapy, with persistently negative proteinuria, stable renal function, a sustained partial tumor response, and no nephrotic relapse. Immunohistochemical staining of the resected primary lung tumor showed no NELL-1 expression.

Conclusions: Resolution of nephrotic syndrome following tumor resection suggests a possible paraneoplastic relationship in this case of NELL-1-positive MN, despite absent NELL-1 expression in the primary tumor. Sustained renal remission during cancer recurrence and atezolizumab therapy suggests that ICI therapy may be feasible in selected patients with resolved paraneoplastic MN under close renal monitoring. This case highlights the importance of malignancy screening in patients with NELL-1-positive MN.