96 Clinical and ACE Genetic Predictors of Incident Chronic Kidney Disease in Non-Diabetic Hypertensive Veterans

Abstract

Chronic kidney disease (CKD; an MDRD estimated GFR <60 ml/min/1.73 m2) is common and is associated with increased morbidity and mortality. The ACE gene has been associated with kidney diseases. We performed a prospective study in non-diabetic hypertensive veterans without CKD recruited from San Diego VA primary care clinics. We used an electronic medical record (EMR) and evaluated functional ACE genetic variants to determine clinical and genetic predictors of incident CKD. Adjusted hazard ratios and concordance statistics for progression to incident CKD (by the MDRD equation) using Cox regression were performed, censoring for death and loss to follow-up, over a mean follow-up of 3.2 years in the entire cohort, and in white and African American subgroups. 768 non-diabetic hypertensive veterans without CKD were included in this study, predominantly male (96.6%) and Caucasian (67.2%). After a mean of 3.2 years, 2.7% died and 35.2% developed incident CKD. We validated that well accepted CKD risk factors, eGFR, hemoglobin, history of cancer and coronary artery disease at the start of the study, and increased number of blood pressure lowering agents were predictors of incident CKD. Additionally, a polymorphism in theACE gene (G2350A; rs4343) was strongly predictive of incident CKD in univariate and multivariate models in the entire sample and in the ethnic specific analyses. In hypertensive non-diabetic veterans, incident CKD was predicted by age, baseline renal function and anemia, and comorbid conditions such as coronary artery disease. Genetic variation within the reninangiotensin system may also play an influential role.