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 µ mol/L=0, K1: 250-450 µ mol/L=4, K2: >450 µ mol/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.

1st Faculty of Medicine Charles University Prague Czechia

Centre for Inflammatory Disease Department of Immunology and Inflammation Imperial College London London United Kingdom

Department of Internal Medicine and IRCCS Ospedale Policlinico San Martino Genova Italy

Department of Medicine University of Cambridge Cambridge United Kingdom

Department of Nephrology General University Hospital Prague Czechia

Department of Pathology and Laboratory Medicine University of North Carolina at Chapel Hill Chapel Hill North Carolina

Department of Pathology Groningen University Medical Center Groningen The Netherlands

Department of Pathology Institute for Clinical and Experimental Medicine Prague Czechia

Department of Pathology Johns Hopkins University School of Medicine Baltimore Maryland

Department of Renal Medicine Vasculitis Clinic Addenbrooke's Hospital Cambridge United Kingdom

Departments of Immunology and Rheumatology Nephrology and Mineral Metabolism Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico City Mexico

Division of Cardiovascular Sciences University of Manchester Manchester United Kingdom

Division of Cell Matrix Biology and Regenerative Medicine University of Manchester Manchester United Kingdom

Division of Nephrology Bursa Uludağ University School of Medicine Bursa Turkey

Division of Nephrology Dialysis and Transplantation University of Genova Genova Italy

Division of Nephrology Johns Hopkins University School of Medicine Baltimore Maryland

Division of Population Health Health Services Research and Primary Care Centre for Biostatistics University of Manchester Manchester United Kingdom

Glasgow Renal and Transplant Unit Queen Elizabeth University Hospital Glasgow United Kingdom

Imperial College Renal and Transplant Centre Hammersmith Hospital Imperial College Healthcare NHS Trust London United Kingdom

Manchester Academic Health Science Centre Manchester University NHS Foundation Trust Manchester United Kingdom

Renal Department Royal Preston Hospital Lancashire Teaching Hospitals NHS Foundation Trust Preston United Kingdom

Renal Department Salford Royal Hospital Northern Care Alliance NHS Foundation Trust Salford United Kingdom

Renal Transplantation and Urology Unit Manchester University NHS Foundation Trust Manchester United Kingdom

Renal Unit Northern Health Victoria Australia

School of Cardiovascular and Metabolic Health University of Glasgow Glasgow United Kingdom

Service de Néphrologie Dialyse Transplantation CHU d'Angers Angers France

Trinity Kidney Centre Trinity College Dublin Dublin Ireland

University BHF Centre for Cardiovascular Science University of Edinburgh and Department of Renal Medicine Royal Infirmary of Edinburgh Edinburgh United Kingdom

University Medical Center Hamburg Eppendorf Institute of Pathology Hamburg Germany

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