The Improved Kidney Risk Score in ANCA-Associated Vasculitis for Clinical Practice and Trials
Authors: Bate Sebastian , McGovern Dominic , Costigliolo Francesca , Tan Pek Ghe , Kratky Vojtech , Scott Jennifer , Chapman Gavin B. , Brown Nina , Floyd Lauren , Brilland Benoit , Martín-Nares Eduardo , Aydın Mehmet Fethullah , Ilyas Duha , Butt Arslan , Nic an Riogh Eithne , Kollar Marek , Lees Jennifer S. , Yildiz Abdülmecit , Hinojosa-Azaola Andrea , Dhaygude Ajay , Roberts Stephen A. , Rosenberg Avi , Wiech Thorsten , Pusey Charles D. , Jones Rachel B. , Jayne David R.W. , Bajema Ingeborg , Jennette J. Charles , Stevens Kate I. , Augusto Jean Francois , Mejía-Vilet Juan Manuel , Dhaun Neeraj , McAdoo Stephen P. , Tesar Vladimir , Little Mark A. , Geetha Duruvu , Brix Silke R. 
Published: December 2023

Significance Statement
Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. More than 1500 patients were collated in an international longitudinal study to revise the ANCA kidney risk score. The score showed satisfactory performance, mimicking the original study (Harrell's C=0.779). In the development cohort of 959 patients, no additional parameters aiding the tool were detected, but replacing the GFR with creatinine identified an additional cutoff. The parameter interstitial fibrosis and tubular atrophy was modified to allow wider access, risk points were reweighted, and a fourth risk group was created, improving predictive ability (C=0.831). In the validation, the new model performed similarly well with excellent calibration and discrimination (n=480, C=0.821). The revised score optimizes prognostication for clinical practice and trials.

Background
Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. A retrospective international longitudinal cohort was collated to revise the ANCA renal risk score.

Methods
The primary end point was ESKD with patients censored at last follow-up. Cox proportional hazards were used to reweight risk factors. Kaplan–Meier curves, Harrell's C statistic, receiver operating characteristics, and calibration plots were used to assess model performance.

Results
Of 1591 patients, 1439 were included in the final analyses, 2:1 randomly allocated per center to development and validation cohorts (52% male, median age 64 years). In the development cohort (n=959), the ANCA renal risk score was validated and calibrated, and parameters were reinvestigated modifying interstitial fibrosis and tubular atrophy allowing semiquantitative reporting. An additional cutoff for kidney function (K) was identified, and serum creatinine replaced GFR (K0: <250 µmol/L=0, K1: 250–450 µmol/L=4, K2: >450 µmol/L=11 points). The risk points for the percentage of normal glomeruli (N) and interstitial fibrosis and tubular atrophy (T) were reweighted (N0: >25%=0, N1: 10%–25%=4, N2: <10%=7, T0: none/mild or <25%=0, T1: ≥ mild-moderate or ≥25%=3 points), and four risk groups created: low (0–4 points), moderate (5–11), high (12–18), and very high (21). Discrimination was C=0.831, and the 3-year kidney survival was 96%, 79%, 54%, and 19%, respectively. The revised score performed similarly well in the validation cohort with excellent calibration and discrimination (n=480, C=0.821).

Conclusions
The updated score optimizes clinicopathologic prognostication for clinical practice and trials.