CKD patients have increased peripheral arterial disease risk

Individuals With Chronic Kidney Disease Have Increased PAD Risk CME

News Author: Marlene Busko
CME Author: Charles Vega, MD, FAAFP

January 17, 2007 — An analysis from the Atherosclerosis Risk in Communities (ARIC) study confirms that patients with chronic kidney disease (CKD) have an increased risk of developing peripheral arterial disease (PAD). Because early PAD detection is critical to prevent leg revascularization and amputation, further studies are needed to see whether PAD screening strategies in CKD patients are effective, researchers conclude.

"The findings of our study call for an increased awareness and early detection of PAD in the CKD population," the group, with lead author Keattiyoat Wattanakit, MD, from the University of Minnesota in Minneapolis, writes. They add that "Recognition of an increased risk for PAD in this population, particularly in individuals with no typical ischemic symptoms, potentially could avert adverse limb as well as cardiovascular disease (CVD) events if modification of risk factors were intensified."

The article is published in the January 10 JASN Express issue of the Journal of the American Society of Nephrology.

The ARIC study cohort comprised 15,792 participants, aged 45 to 64 years at baseline in 1987 to 1989, who were recruited in 4 communities in the United States. The current study included 14,280 participants who had no PAD, defined as an ankle-brachial index of 0.9 or higher, or intermittent claudication at baseline.

Study Highlights

• Participants were between the ages of 45 and 64 years and were of white or black race. No subject had PAD, defined by an ankle-brachial index of 0.9 or higher, at baseline.
• GFR was estimated by applying serum creatinine levels to the Modification of Diet in Renal Disease formula. Subjects were divided into 3 groups, according to GFR: more than 90 mL/minute per 1.73 m² (normal kidney function), 60 to 89 mL/minute per 1.73 m² (mildly decreased kidney function), and 15 to 59 mL/minute per 1.73 m² (chronic kidney disease).
• The main study outcome was the relationship between kidney function and the risk for PAD, which was diagnosed by a finding of ankle-brachial index less than 0.9; new intermittent claudication symptoms; or a hospital discharge diagnosis of PAD, leg amputation, or leg revascularization procedure. Only a random subgroup of participants had ankle-brachial measurements performed during the course of the study. The main study result was adjusted for the presence of existing cardiovascular risk factors, as well as glucose and lipid levels.
• 14,280 individuals comprised the study cohort. Mean age of the subjects was 54 years, and 55% of the cohort was women.
• The mean follow-up time was 13.1 years. During this period, 1016 subjects developed PAD. Nearly half of cases were found because of a low ankle-brachial index. Patients with PAD were more likely to be older and have diabetes and other cardiovascular risk factors.
• After adjustment for age, sex, race, and study center, the rates of incident PAD were 4.7, 4.9, and 8.6 per 1000 person-years among subjects with normal kidney function, mildly decreased kidney function, and CKD, respectively. The adjusted risk for PAD began to increase in linear fashion after eGFR fell below 75 mL/minute per 1.73 m².
• Compared with normal kidney function, mildly decreased kidney function did not significantly and independently increase the risk for PAD.
• Conversely, compared with normal kidney function, CKD was associated with a multivariate-adjusted relative risk of 1.56 for PAD.
• Examining subgroups of patients based on age and chronic disease failed to significantly alter the study's main findings. Reduced GFR was a particularly strong risk factor for PAD among men vs women.
• In a separate analysis, kidney disease was not related to the risk for asymptomatic PAD diagnosed by reduced ankle-brachial index scores alone. CKD remained a significant risk factor for symptomatic PAD.

Pearls for Practice

• Previous research has demonstrated that reduced renal function is an independent risk factor for cardiovascular disease, although the precise mechanisms of this association are unclear. Reduced renal function might also increase the risk for PAD among postmenopausal women.
• The current study found that an eGFR between 15 and 59 mL/minute per 1.73 m² (chronic kidney disease) is an independent risk factor for incident PAD, but that an eGFR between 60 and 89 mL/minute per 1.73 m² (mildly decreased kidney function) was not a risk factor for PAD.