Peripheral artery disease and risk of kidney outcomes: The Atherosclerosis Risk in Communities (ARIC) study

Abstract

Background and aims: The potential impact of peripheral artery disease (PAD) on kidney outcomes is not well understood. The aim of this study was to explore the association between PAD and end-stage kidney disease (ESKD) and chronic kidney disease (CKD).

Methods: Among 14,051 participants (mean age 54 [SD 6 years]) from the Atherosclerosis Risk in Communities study, we categorized PAD status as symptomatic PAD (intermittent claudication or leg revascularization), asymptomatic PAD (ankle-brachial index [ABI] ≤0.90 without clinical history of symptoms), and ABI 0.91-1.00, 1.01-1.10, 1.11-1.20 (reference), 1.21-1.30, and >1.30. We evaluated their associations with two kidney outcomes: ESKD (the need of renal replacement therapy or death due to kidney disease) and CKD (ESKD cases or an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² with a ≥25 % decline from the baseline) using multivariable Cox proportional hazards models.

Results: Over ∼30 years of follow-up, there were 598 cases of incident ESKD and 4686 cases of incident CKD. After adjusting for potential confounders, both symptomatic PAD and asymptomatic PAD conferred a significantly elevated risk of ESKD (hazard ratio 2.28 [95 % confidence interval 1.23-4.22] and 1.75 [1.19-2.57], respectively). Corresponding estimates for CKD were 1.54 (1.14-2.09) and 1.63 (1.38-1.93). Borderline low ABI 0.91-1.00 also showed elevated risk of adverse kidney outcomes after adjustment for demographic variables. Largely consistent results were observed across demographic and clinical subgroups.

Conclusions: Symptomatic PAD and asymptomatic PAD were independently associated with an elevated risk of ESKD and CKD. These results highlight the importance of monitoring kidney function in persons with PAD, even when symptoms are absent.

Keywords: Ankle-brachial index; Atherosclerosis; Chronic kidney disease; End-stage kidney disease; Peripheral artery disease.

Figure 1:

Cumulative incidence of (A) ESKD and (B) CKD. Figure illustrates the cumulative incidence of ESKD and CKD by symptomatic PAD status and ABI category over 30 years. Participants with PAD, regardless of symptoms, had the highest cumulative incidence over time. Abbreviations: ABI = ankle-brachial index, CKD = chronic kidney disease, ESKD = end-stage kidney disease, PAD = peripheral artery disease

Figure 2:

Adjusted hazard ratio of (A) ESKD and (B) CKD. Using cubic splines, figure shows the association between ABI and both kidney outcomes in participants without symptomatic PAD. There was a dose-response relationship. Hazard ratios in reference to ABI of 1.15 and adjusted for sex, age, race, study site, education level, body mass index, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, diastolic blood pressure, systolic blood pressure, antihypertensive medication, drinking status, smoking status, diabetes, stroke, prevalent coronary heart disease, and prevalent heart failure. Restricted cubic spline created with knots at the 5, 35, 65, and 95 percentiles of ABI. Includes only participants without symptomatic peripheral artery disease Abbreviations same as Figure 1.

Figure 3:

Hazard ratios of (A) ESKD and (B) CKD. Subgroup analyses highlight that the association between PAD status and both ESKD and CKD were largely consistent. However, for CKD there was a stronger association among males compared to females. Adjusted for sex, age, race, study site, education level, body mass index, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, diastolic blood pressure, systolic blood pressure, antihypertensive medication, drinking status, smoking status, diabetes, stroke, prevalent coronary heart disease, and prevalent heart failure, PAD ABI = ankle-brachial index, PAD = peripheral artery disease, CI = confidence interval PAD defined as symptomatic PAD or asymptomatic PAD (ABI ≤ 0.90), No PAD defined as all other ABI values

Figure 4.

Asymptomatic and symptomatic PAD increase the risk of ESKD and CKD. Using data from over 14,000 patients, we found that both asymptomatic and symptomatic peripheral artery disease increased the risk of end-stage kidney disease and chronic kidney disease by approximately 2x and 1.5x, respectively, after adjusting for potentially confounding variables.