A validated multivariable machine learning model to predict cardio-kidney risk in diabetic kidney disease.

Background: Individuals with diabetic kidney disease (DKD) often suffer cardiac and kidney events. We sought to develop an accurate means by which to stratify risk in DKD.

Methods: Clinical variables and biomarkers were evaluated for their ability to predict the adjudicated primary composite endpoint of CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) by 3 years. Using machine learning techniques, a parsimonious risk algorithm was developed.

Results: The final model included age, body-mass index, systolic blood pressure, and concentrations of N-terminal pro-B type natriuretic peptide, high sensitivity cardiac troponin T, insulin-like growth factor binding protein-7 and growth differentiation factor-15. The model had an in-sample C-statistic of 0.80 (95% CI = 0.77-0.83; P < 0.001). Dividing results into low, medium and high risk categories, for each increase in level the hazard ratio increased by 3.43 (95% CI = 2.72-4.32; P < 0.001). Low risk scores had negative predictive value of 94%, while high risk scores had positive predictive value of 58%. Higher values were associated with shorter time to event (log rank P < 0.001). Rising values at 1 year predicted higher risk for subsequent DKD events. Canagliflozin treatment reduced score results by 1 year with consistent event reduction across risk levels. Accuracy of the risk model was validated in separate cohorts from CREDENCE and the generally lower risk Canagliflozin Cardiovascular Assessment Study.

Conclusions: We describe a validated risk algorithm that accurately predicts cardio-kidney outcomes across a broad range of baseline risk.

Trial registration: CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation; NCT02065791) and CANVAS (Canagliflozin Cardiovascular Assessment Study; NCT01032629/NCT01989754).