Clinicopathological features of ANCA-associated glomerulonephritis with membranous nephropathy lesions: A single-center cohort study in Japan

ANCA-associated glomerulonephritis (AAGN) is generally characterized by pauci-immune necrotizing crescentic glomerulonephritis without glomerular immune complex deposition. However, electron microscopy may reveal immune deposits in the mesangial and subepithelial areas, presenting as partial membranous nephropathy (MN) lesions, with granular IgG deposition along the glomerular basement membrane (GBM) observed by immunofluorescence. Reported antigens associated with AAGN presenting with MN lesions include PLA2R and MPO. Because of its rarity, AAGN with MN lesions has been limited to small case series and reports, leaving its clinical and histopathological features unclear. This study aims to clarify the clinicopathological characteristics of MPO-associated cases among patients with AAGN accompanied by MN lesions in our single-center cohort.

This retrospective observational study involved data collection and analysis based on medical records and kidney biopsy reports. The subjects were 7,017 patients who underwent kidney biopsy in our single-center cohort between January 1999 and July 2025. Among these, cases of AAGN with MN lesions were extracted. Renal tissues were immunohistochemically stained with an anti-MPO antibody. Statistical analysis was performed to compare clinical and pathological findings between two groups: an MPO-positive group (granular MPO deposition on GBM) and an MPO-negative group (without it). Univariate analysis was performed using the Wilcoxon rank-sum test for continuous variables and Pearson's chi-square test for categorical variables.

Of the 7,017 cases, 28 (0.4%) were identified as AAGN with MN lesions. Among these 28 cases, 5 (17.9%) showed granular deposition of MPO along the GBM. Regarding clinical features (n=28), the median age was 71.0 years (IQR, 66.3-78.5), 17 (60.7%) were female, the median estimated glomerular filtration rate (eGFR) was 26.8 mL/min/1.73m2 (IQR, 9.8-67.9), and the median C-reactive protein (CRP) was 0.49 mg/dL (IQR, 0.11-3.52). Regarding pathological findings (n=28), the median percentage of cellular crescents was 14.8% (IQR, 0.0-29.4), and the median percentage of globally sclerotic glomeruli was 18.3% (IQR, 11.2-35.0). Comparing MPO-positive (n=5) and MPO-negative (n=23) groups, no significant differences were observed in eGFR (49.2 vs 18.4 mL/min/1.73m2, p=0.215) or CRP (0.32 vs. 0.80 mg/dL, p=0.380). However, a statistically significant difference was observed in the percentage of cellular crescents (50.0 vs 4.5%, p=0.033). No significant differences were found in the percentage of globally sclerotic glomeruli, Interstitial Fibrosis and Tubular Atrophy (IFTA), or inflammatory cell infiltration.

In this study, granular deposition of MPO along the GBM was observed in approximately 18% of patients with AAGN with MN lesions. Furthermore, a significant difference in the percentage of cellular crescents was noted among pathological features, suggesting severe glomerular inflammation in MPO-positive group. This finding suggests that the severity of glomerular injury in AAGN with MN lesions may differ depending on the type of antigen deposited on the GBM. Consequently, heightened clinical vigilance is warranted, particularly in cases where MPO is the antigen.