ADA Scientific Sessions 2025 Abstract · Jun 13, 2025
Baseline Risk and Longitudinal Changes in KidneyIntelX Scores and Their Association with Kidney Outcomes in the CANVAS and CREDENCE Trials
By MOEDT E, COCA S, FLEMING F et al.
Introduction and Objective: KidneyIntelX is a composite risk score incorporating biomarkers and clinical variables at baseline for diabetic kidney disease (DKD) progression. We sought to determine the clinical relevance of KidneyIntelX and thresholds in a large cohort of patients with type 2 diabetes and a broad range of CKD. Methods: We measured tumor necrosis factor receptor (TNFR)-1), TNFR-2, and kidney injury molecule (KIM-1) on banked plasma samples from CANVAS and CREDENCE participants, and executed kidneyintelX.dkd at baseline and year 1. We assessed the association of baseline and changes in kidneyintelX.dkd with a composite kidney outcome of 40% decline in eGFR or kidney failure. Hazard ratios were estimated using multivariate Cox regression. Results: There were 4677 participants (mean eGFR 69.4 mL/min/1.73m2; median UACR 77.0 mg/g) with available plasma samples. At baseline, kidneyintelX.dkd scored 867 (18.5%) as high, 1520 (32.5%) as moderate, and 2290 (49.0%) as low risk. The adjusted HR per doubling in predicted probability was 2.26 (95% CI 1.80-2.84). At year 1, the median change in KidneyIntelX predicted probabilities was 0.0%, with >10% reduction in 25.6% of canagliflozin- vs. 17.0% of placebo-treated patients. The adjusted HR for the change in predicted probability from baseline to year 1 was 2.24 (95% CI 1.65-3.04). Canagliflozin led to more patients shifting to lower risk at year 1 (32.1% vs. 16.2% moderate to low; 38.9% vs 19.7% high to moderate or low). Low risk at year 1 was associated with very low kidney outcome risk of 0.3 events per 100 person-years, while staying at moderate had 1.4, moving from high to moderate had 2.2, and high risk at year 1 had 8.9. Conclusion: Baseline and year 1 KidneyIntelX risk assessments in patients with type 2 diabetes and CKD robustly stratified patients for DKD progression independently of classic predictors and should be considered for enriching clinical trials and assessing treatment response. Disclosure: E. Moedt: None. S. Coca: Consultant; Renalytix, Bayer Pharmaceuticals, Inc, Alexion Pharmaceuticals, Inc, Vera Therapeutics, Mylan. F. Fleming: Employee; Renalytix. H.L. Heerspink: Consultant; Alnylam Pharmaceuticals, Inc, Alexion Pharmaceuticals, Inc, AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Eli Lilly and Company, Janssen Pharmaceuticals, Inc, Novartis AG, Novo Nordisk A/S, Roche Pharmaceuticals, Traveere Pharmaceuticals, Menarini.