Combined Effect of Chronic Kidney Disease and Peripheral Arterial Disease on All-Cause Mortality in a High-Risk Population

Background and objectives: Chronic kidney disease (estimated glomerular filtration rate <60 ml/min per 1.73 m²) and peripheral arterial disease (ankle-brachial index <0.9) independently predict mortality. It was hypothesized that the risk for death is higher in patients with both chronic kidney disease and peripheral arterial disease compared with those with chronic kidney disease or peripheral arterial disease alone.Design, setting, participants, & measurements: A total of 1079 patients who had an ankle-brachial index and serum creatinine recorded within 90 d of each other in 1999 were studied retrospectively. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease equation. Patients were categorized into four groups: Chronic kidney disease and peripheral arterial disease, chronic kidney disease alone, peripheral arterial disease alone, or no chronic kidney disease or peripheral arterial disease.Results: The overall 6-yr mortality rate was 28% (n = 284). Patients with both chronic kidney disease and peripheral arterial disease had the highest mortality rate (45%) compared with patients with chronic kidney disease alone (28%), peripheral arterial disease alone (26%), and neither condition (18%). After adjustment for clinical and demographic variables, the chronic kidney disease and peripheral arterial disease group had an increased odds for death when compared with the no chronic kidney disease or peripheral arterial disease group or the single disease groups.Conclusions: These findings indicate that patients with both chronic kidney disease and peripheral arterial disease have a significantly higher risk for death than patients with either disease alone.Both peripheral arterial disease (PAD) and chronic kidney disease (CKD) are prevalent in the general population, especially in patients who are older than 65 yr and have other cardiovascular risk factors. The data from the Third National Health and Nutrition Examination Survey (NHANES III) suggest that there are more than 8 million people in the United States with reduced kidney function (defined by a GFR <60 ml/min per 1.73 m²) (1). PAD is a common disease with a prevalence rate of 14.5% among those aged ≥70 yr and affects approximately 5 million adults aged ≥40 yr in the United States (2).According to recent reports, even mild to moderate CKD is a powerful independent predictor of cardiovascular mortality and all-cause mortality (3–9). Despite the current recommendation for regular laboratory testing for serum creatinine in patients who are at increased risk for CKD (elderly, those with diabetes, and those with cardiovascular disease [CVD] or other CVD risk factors), the frequency of testing is still significantly low and therefore results in underdetection (10). Moreover, patients with CKD are at an increased risk for cardiovascular events and mortality yet often receive inadequate disease prevention and management (11–13).Like CKD, PAD is underdiagnosed and undertreated in the general population (14,15). An ankle-brachial index (ABI) cutoff of <0.9 not only has been shown to be a good screening tool for PAD (90% sensitivity and 98% specificity) (14,16) but is also associated with increased cardiovascular and all-cause mortality (17–20).PAD is very common in the CKD population (GFR <60 ml/min) with prevalence rates of 24 to 37% (21–23). Both CKD and PAD share the same cardiovascular risk factors and are clinical manifestations of diffuse atherosclerosis. Patients with PAD and ESRD have increased mortality and morbidity. These individuals may present with critical limb ischemia, which is associated with lower successful revascularization rates and higher mortality (24–27); however, the mortality data on PAD in the earlier stages of CKD is still limited. One recent study by O''Hare et al. (28) reported that moderate to severe predialysis CKD significantly increases mortality in patients with advanced PAD; however, that study was limited by its short follow-up (1 yr) and that the PAD population contained only those with advanced PAD (rest pain, ischemic ulceration, or gangrene). In this study, we hypothesized that the risk for death is higher in patients with both CKD and PAD than in those with CKD or PAD alone.