Multicentre comparative study of neural epidermal growth factor-like 1 protein vs M-type phospholipase A2 receptor-associated membranous nephropathy

BACKGROUND The understanding of membranous nephropathy (MN) has significantly evolved with the discovery of novel antigenic targets. M-type phospholipase A2 receptor-associated MN (PLA2R-MN) is the most common antigenic variant, followed by neural epidermal growth factor-like 1 protein-associated MN (NELL1-MN). Few studies have directly compared the outcomes of these two variants. AIM To compare the outcomes of NELL1-MN with PLA2R-MN. METHODS In this retrospective cohort study, we compared the outcomes of NELL1-MN and PLA2R-MN using time-to-event analysis. Rate of remission - complete or partial - was the primary outcome of interest. RESULTS The 17 patients diagnosed with NELL1-MN during the study period were compared with 24 patients with PLA2R-MN diagnosed during the same month. Antecedent exposure to traditional indigenous medicines was more common in NELL1-MN than PLA2R-MN (70.6% vs 13%, P < 0.001). 11.8% with NELL1-MN had rheumatoid arthritis while none with PLA2R-MN had the same (P = 0.08). NELL1-MN showed a significantly higher remission-rate than PLA2R-MN (11.7 per 100-patient-months vs 5 per 100-patient-months, P = 0.01) and a shorter time-to-remission than PLA2R-MN (median: 7 months vs 13 months, P = 0.001). In multivariate Cox-regression, NELL1-MN was independently associated with a higher likelihood of remission compared with PLA2R-MN (hazard ratio = 2.65; 95% confidence interval: 1.25-5.64; P = 0.01). Spontaneous remission-rate was higher for NELL1-MN than PLA2R-MN (3.4 per 100-patient-months vs 0.3 per 100-patient-months, P = 0.01). Resistant nephrotic syndrome was more common among PLA2R-MN than NELL1-MN (2.5 per 100-patient-months vs 0 per 100-patient-months, P = 0.04). CONCLUSION NELL1-MN has a favourable prognosis compared to PLA2R-MN. Antigen-specific outcomes research could inform prognosis and guide treatment strategies in MN.