DYNAMIC INSIGHTS INTO THERAPEUTIC STRATEGIES AND LONGITUDINAL OUTCOMES: A RETROSPECTIVE ANALYSIS OF NELL1 POSITIVE MEMBRANOUS NEPHROPATHY COHORT

Introduction:

Membranous Nephropathy (MN) is a rare autoimmune disease in which circulating autoantibodies attack podocytes. Until recently, target antigen in almost all secondary MN cases was unknown. Neural epidermal growth factor like 1 (NELL1) is second most common antigen, following phospholipaseA2 receptor (PLA2R).  Emerging evidence suggests role of complementary and alternative medicine (CAM) and malignancies. Currently, very little information is available regarding treatment and clinical outcomes in patients with non–malignancy-related NELL1-MN.

Methods:

This retrospective descriptive study describes patients with biopsy proven NELL1-MN diagnosed in our nephrology department between 1st April 2021 and 31st March 2023. They were traced from hospital records and were profiled in terms of their demographic and histological characteristics. Treatment history along with baseline and last available serum albumin, creatinine, and proteinuria was recorded.

Inclusion Criteria:

a.     Age more than 18 years with biopsy proven NELL1-MN and atleast one year of disease duration

b.    Patient willing to give consent

Exclusion criteria:

a.     MN with any identifiable antigen other than NELL1 on Immunohistochemistry

b.     CKD stage 3 or above at presentation

c.       Patients with lupus nephritis or other connective tissue disorders.

Results:

We had a total of 15 patients with NELL1-MN, but only 10 patients were included in study. There was no sex predilection and mean age of 37.2±15.2 years. The duration of follow up since biopsy was 12 to 33 months. In our study, three(30%) had history of consuming CAM. Another three(30%) had history of prolonged NSAID intake as an over-the-counter pain killer. No patient had any history of skin fairness cream use, any identifiable malignancy or autoimmune disease.

In our study, 100% patients had IgG1 and IgG4 positivity with IgG1 predominance over IgG4 in 20% and IgG1-IgG4 co-dominance in 80%. C3 positivity was seen in 70% and segmental staining in 30%. The mean 24 hr Urine Protein (mg/day) at time of biopsy was 6502.7±4154.4 and last report available after treatment  was 543.7±588.Three cases were managed conservatively and all achieved complete remission(CR) (30%) with mean follow up duration of 23.67±7.76 months. Seven patients required immunosuppression with Calcineurin Inhibitor(CNI) and steroids for 6 to 12 months with mean treatment duration of 9.3±2.5 months. Out of these, two (20%) achieved CR, four (40%) achieved Partial Remission (PR) and one was CNI resistant, requiring cyclical cyclophosphamide-corticosteroid(10%). This patient eventually had decline of renal function.

This study is not without its limitations like retrospective nature, small sample size, brief follow-up duration, dearth of information regarding nature of CAM, non-usage of rituximab and absence of antibody monitoring.

Conclusions:

NELL1-MN demonstrates an association with CAM and NSAID intake, with possible role of heavy metals, and not with malignancy, as previously thought. Some patients may undergo spontaneous or complete remission with elimination of inciting factor or with effective RAAS inhibition respectively. Our study showed, a good response to supportive therapy and oral CNI therapy with CR/PR in 90% cases, thus, pointing to avoidance of cytotoxic agents and biologics as first line, to prevent unnecessary side effects.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.