BACKGROUND: Exostosin 1/2 (EXT1/2) and neural cell adhesion molecule 1 (NCAM1) associated membranous lupus nephritis (MLN) may represent distinct disease phenotypes with prognostic significance. METHODS: We searched our archives for patients with systemic lupus erythematous (SLE) and at least two kidney biopsies demonstrating MLN. Each biopsy was stained for EXT1 and NCAM1 and scored as positive or negative. Histopathologic and clinical data were reviewed. RESULTS: We identified 31 patients with a clinical diagnosis of SLE and at least two kidney biopsies with MLN. A total of 28 patients (90%) showed concordant staining for EXT1 and NCAM1 in both biopsies; 8 patients (26%) were EXT1 positive and NCAM1 negative, 18 patients (58%) were EXT1 negative and NCAM1 negative and 2 patients (7%) were EXT1 negative and NCAM1 positive. A total of three patients (10%) had discordant EXT1 staining between their first and last biopsies; two patients (7%) were EXT1 positive in their first biopsy and EXT1 negative in the last biopsy and one patient (3%) was EXT1 negative in his first biopsy and EXT1 positive in the last biopsy. Compared with the EXT1-negative cohort at the time of the first biopsy, the EXT1-positive cohort had a higher average estimated glomerular filtration rate (eGFR; 141 versus 108 mL/min/1.73 m2; P = 0.04), lower average percent global glomerulosclerosis (0.5 versus 12%; P = 0.05), lower average interstitial fibrosis and tubular atrophy (2.5 versus 11.7%; P = 0.06) and lower average total National Institutes of Health (NH) chronicity scores (0.75 versus 2.33; P = 0.05). On long-term follow-up, the rate of change in eGFR did not significantly differ between the two groups (P = 0.24). One EXT1-positive patient (12.5%) developed stage 4 chronic kidney disease (CKD) or end-stage kidney disease (ESKD) compared with four patients (20%) in the EXT-negative group and two of the three EXT1-discordant patients (P = 0.38). CONCLUSIONS: We performed the largest retrospective repeat-biopsy study to evaluate EXT1 and NCAM1 autoantigens in MLN. Our data demonstrate that EXT1 positivity is associated with better kidney function at the time of diagnosis and raises the possibility that EXT1 status may change throughout the disease course of MLN.