Abstract
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: 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: = 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.