Pauci-immune glomerulonephritis: Does negativity of anti-neutrophilic cytoplasmic antibodies matters?

Abstract

Aim: A significant proportion of pauci-immune glomerulonephritis (PIGN) patients are reported to have absence of anti-neutrophilic cytoplasmic antibodies (ANCA). However, studies are controversial regarding their significance and there is limited data after the new prognostic classification of PIGN. Methods: Renal biopsy-proven cases of PIGN were included and their clinical details, ANCA status by immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA), Birmingham Vasculitis Activity Score (BVAS) and treatment outcomes at 6months were noted. The renal biopsies were classified according to the proposed histopathological classification. Scoring was done from 0-3 for interstitial edema, interstitial fibrosis and tubular atrophy (IFTA), interstitial inflammation and arteriosclerosis. The percentage of glomeruli with sclerosis, cellular and fibrous crescents, and percentage of subjects with glomerulitis, tuft necrosis, interstitial granuloma and vasculitis were noted. Results: Out of the 84 subjects included in the study, 33 (39.3%) were negative for ANCA by both IIF and ELISA. These subjects had significantly higher renal involvement, less extra-renal manifestations and lower BVAS. On histology, they had significantly higher proportion of crescentic class (66.7% vs. 41.2%, P=0.039), higher number of cellular crescents (66.12% vs. 53.3%, P=0.00008), higher IFTA (1.53 vs. 1.02, P=0.009) and less interstitial edema (1.44 vs. 1.96, P=0.003). The treatment outcomes were worse in ANCA-negative PIGN subjects, with significantly less improvement (37.2% vs. 62.8%, P=0.02), more deterioration (40.7% vs. 14%, P=0.006), and reduced probability of becoming dialysis free (31.6% vs. 69.6% P=0.009). Conclusions: A negative ANCA in PIGN is associated with crescentic class, more IFTA and poor treatment outcomes.