ABSTRACT: BACKGROUND:Low ankle-brachial index (ABI) is associated with increases in serum creatinine level. Whether low ABI is associated with the development of rapid estimated glomerular filtration rate (eGFR) decline, stage 3 chronic kidney disease (CKD), or microalbuminuria is uncertain. STUDY DESIGN:Prospective cohort study. SETTING & PARTICIPANTS:Framingham Offspring cohort participants who attended the sixth (1995-1998) and eighth (2005-2008) examinations. PREDICTOR:ABI, categorized as normal (>1.1 to <1.4), low-normal (>0.9 to 1.1), and low (?0.9). OUTCOMES:Rapid eGFR decline (eGFR decline ?3 mL/min/1.73 m(2) per year), incident stage 3 CKD (eGFR <60 mL/min/1.73 m(2)), incident microalbuminuria. MEASUREMENTS:GFR was estimated using the serum creatinine-based CKD-EPI (CKD Epidemiology Collaboration) equation. Urinary albumin-creatinine ratio (UACR) was determined based on spot urine samples. RESULTS:During 9.5 years, 9.0% (232 of 2,592) experienced rapid eGFR decline and 11.1% (270 of 2,426) developed stage 3 CKD. Compared to normal ABI, low ABI was associated with 5.73-fold increased odds of rapid eGFR decline (95% CI, 2.77-11.85; P<0.001) after age, sex, and baseline eGFR adjustment; this persisted after multivariable adjustment for standard CKD risk factors (OR, 3.60; 95% CI, 1.65-7.87; P = 0.001). After adjustment for age, sex, and baseline eGFR, low ABI was associated with a 2.51-fold increased odds of stage 3 CKD (OR, 2.51; 95% CI, 1.16-5.44; P = 0.02), although this was attenuated after multivariable adjustment (OR, 1.68; 95% CI, 0.75-3.76; P = 0.2). In 1,902 free of baseline microalbuminuria, low ABI was associated with increased odds of microalbuminuria after adjustment for age, sex, and baseline UACR (OR, 2.81; 95% CI, 1.07-7.37; P = 0.04), with attenuation upon further adjustment (OR, 1.88; P = 0.1). LIMITATIONS:Limited number of events with low ABI. Outcomes based on single serum creatinine and UACR measurements at each examination. CONCLUSIONS:Low ABI is associated with an increased risk of rapid eGFR decline, suggesting that systemic atherosclerosis predicts a decrease in kidney function.
