Abstract MP09: Indices of Kidney Tubular Health Improve Cardiovascular Disease Risk Prediction in Adults With Hypertension and Chronic Kidney Disease in SPRINT

Abstract

Introduction: While chronic kidney disease (CKD) is a strong risk factor for cardiovascular disease (CVD), traditional metrics of kidney function (eGFR and albuminuria) have not improved CVD risk prediction equations. We hypothesize that new measures of kidney tubular function and injury can improve CVD risk prediction. Methods: Of 1971 SPRINT participants with eGFR <60mL/min/1.73m 2 and without CVD at baseline, we analyzed 1858 with urine and serum biomarkers. We conducted factor analysis on 10 kidney tubule biomarkers using principal-component factor estimation and promax rotation. To examine the association between the factor scores and risk of subsequent cardiovascular events, we used adjusted Cox models. Using Harrell’s C-statistic, we compared a standard CVD risk prediction model to models adding 1) factor scores of kidney tubular health, 2) eGFR and albumin-to-creatinine ratio (ACR), and 3) factor scores, eGFR and ACR. We also conducted these comparisons using ASCVD predicted risk in place of CVD risk factors among those <80 years. Results: Mean age was 73, 44% female, 29% black, and mean±SD eGFR was 45±12 mL/min/1.73m 2 . Factor analysis identified 4 unique dimensions of kidney tubular health that correspond to hypothesized physiologic processes ( Table ). Three of four factors were associated with CVD in demographic models, and Factors 3 and 4 remained associated in the full model. The C-statistic of the base CVD risk equation was 0.670, and with inclusion of the four kidney tubule factors the C-statistic improved to 0.727 (p for difference <0.0001), a larger increase than addition of eGFR and ACR to the base model (c=0.711, p for difference=0.0007). Addition of eGFR and ACR to the kidney tubule model did not improve discrimination (c=0.730, p for difference=0.17). Results were similar with ASCVD predicted risk. Conclusion: Indices of kidney tubular health based on urine and serum biomarkers may improve CVD risk prediction in adults with hypertensive CKD. Further studies are needed in the general, non-CKD population.