499-P: Clinical Validation of an AI-Enabled Prognostic Test (KidneyintelX) to Accurately Predict Rapid Kidney Function Decline in Patients with Type 2 Diabetic Kidney Disease

The ability to predict rapid kidney function decline (RKFD) in patients with early stages of type 2 diabetic kidney disease (T2DKD) can improve long-term health outcomes through earlier intervention. Our objective was to develop a robust risk score for patients with early stages of T2DKD. We obtained EHR and plasma from patients with T2DKD (Kidney Disease Improving Global Outcomes [KDIGO] G1-G2, A2-A3 or G3a-G3b, A1-A3) from the Mount Sinai BioMe Biobank and the Penn Medicine Biobank and measured soluble tumor necrosis factor receptor (sTNFR1, sTNFR2) and kidney injury molecule-1 (KIM-1) via a validated quantitative electrochemiluminescent assay. A machine learning model was trained using the EHR/biomarker data to predict RKFD, defined as eGFR decline of ≥5 ml/min/year or ≥40% sustained decline in eGFR or kidney failure within 5 years, and performance was compared to a clinical model and KDIGO risk-matrix. A total of 1146 subjects with a mean age of 63, baseline eGFR 54 ml/min, and median UACR 61 mg/g were randomly divided into 60% training (n=686) and 40% validation (n=460) sets. The median follow-up was 4.3 years and 241 (21%) experienced RKFD. The AUC of KidneyIntelX for RFKD was 0.85 (95% CI 0.84-0.86) in training and 0.77 (95% CI 0.76-0.79) in the validation set vs. AUC of 0.67 (95% CI 0.64-0.70) for a clinical model. Using pre-specified cutoffs from the training set, KidneyIntelX stratified 47%, 37% and 16% of the validation set into low-, intermediate- and high-risk strata, with a PPV of 62% (vs. 41% for KDIGO) in the high-risk group (p <0.001), a net reclassification improvement for events of 41% (p <0.05), and a NPV of 91% in the low-risk group (vs. 85% for KDIGO). KidneyIntelX, a machine learning model combining biomarkers and EHR data, improved prediction of RKFD over standard clinical metrics in patients with T2DKD. Future studies will prospectively evaluate KidneyIntelX in clinical decision-making and impact.