The percentage of normal glomeruli (“Normal glomerular score”) predicts kidney outcome in ANCA vasculitis

Background In the management of Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, accurate prognostication of renal outcome is critical. However, the clinical utility of highly precise multi-variable models, such as the ANCA Kidney Risk Score (AKRiS), is often hampered by their complexity. This study aimed to validate a simple alternative: the “Normal” Glomerular Score (NGS), defined as the percentage of normal glomeruli. Methods We retrospectively analyzed 188 consecutive patients with biopsy-proven AAV-GN from a single European center (2001–2024). Patients were categorized by NGS: high (>50%), moderate (26-50%), low (10-25%), and very low (<10%). We assessed concordance between NGS, Berden classification, and AKRiS to determine if NGS serves as a valid proxy for complex systems. The primary endpoint was death-censored progression to end-stage renal disease (ESKD). Results The NGS strongly indicated presentation renal function; median eGFR was 31.4 ml/min in the high NGS group vs. 10.8 ml/min in the low cohort (p<0.001). It correlated moderately-to-strongly with AKRiS (Rho=-0.714, p<0.001). Over a 46.6-month median follow-up, dialysis rates were 12.8%, 23.7%, 42.9%, and 42.6% in the high-, moderate-, low-, and very low-NGS groups (p=0.003). There was no statistical difference in dialysis rates (p=0.98) or long-term eGFR (28 vs. 30 ml/min, p=0.51) between the low and very low groups, indicating a prognostic plateau below 25% normal glomeruli. Cox regression showed a significant hazard ratio for dialysis of 1.432 with each worsening category (95% CI: 1.144-1.792). The NGS achieved a C-index of 0.812, statistically inferior to AKRiS (0.831). Sub-analysis of post-2015 patients confirmed NGS’s prognostic validity with modern Rituximab-based induction. Conclusion NGS predicts long-term renal survival in AAV-GN. While not replacing multi-variable models like AKRiS for precise risk assessment in clinical trials, it offers a rapid, accessible estimation of functional nephron mass for bedside stratification.