Clinical and pathological characteristics of NELL-1-positive membranous nephropathy: a case series study

This study aimed to comprehensively characterize the clinical and pathological features, treatment strategies, and outcomes of patients with neural epidermal growth factor-like 1 protein (NELL-1)-positive membranous nephropathy (MN).

We retrospectively analyzed non-systemic lupus erythematosus (SLE) MN patients diagnosed between January 2010 and August 2021 at Cangzhou Central Hospital, China. Inclusion required negative PLA2R and THSD7A staining and available paraffin-embedded renal tissue. Clinical, laboratory, pathological, treatment, and outcome data were collected and analyzed descriptively.

Among 531 non-SLE MN cases screened, 23 patients (13 males, 10 females; mean age 49.4 ± 12.0 years) were identified as NELL-1(+), PLA2R(-), and THSD7A(-). Hypertension was present in 26.1%, and nephrotic syndrome in 60.9% of patients. Bright granular NELL-1 deposits along glomerular capillary loops were observed in all cases, with segmental or incomplete global distribution seen in 65.2%. IgG4 and IgG1 were the predominant immunoglobulin subclasses (82.6 and 78.2%, respectively). Over a median follow-up of 56 months, 73.9% received immunosuppressive therapy, while 26.1% were managed with supportive treatment alone. The overall remission rate was 87.0% (73.9% complete, 13.0% partial), with only two patients experiencing transient renal function decline and none progressing to end-stage renal disease. Notably, 26.1% of patients developed malignancies, most commonly lung cancer. In patients with malignancy, tumor resection and supportive therapy alone frequently led to remission of MN.

NELL-1-positive MN is characterized by high rates of IgG1 and IgG4 deposition and generally favorable responses to therapy. A substantial proportion of patients were diagnosed with malignancy, highlighting the importance of cancer screening in this population. Timely identification and management of underlying malignancy may contribute to improved renal outcomes.