Relationship between kidney disease and endothelial function in peripheral artery disease

Abstract

Objective We have previously shown that peripheral artery disease (PAD) is associated with marked impairment of endothelial function (EF). Given that poor EF is associated with functional status of PAD patients as well as increased morbidity and mortality in patients undergoing vascular procedures, determining factors associated with poor EF in a PAD cohort is important. We hypothesized that decreased kidney function is associated with impaired endothelial function (EF) in patients with PAD. Methods This was a cross-sectional study of PAD patients presenting to a vascular surgery outpatient clinic at the San Francisco Veterans Affairs Medical Center including patients enrolled into the OMEGA-PAD I trial (NCT01310270) and the OMEGA-PAD Cohort. Brachial artery flow-mediated vasodilation (FMD) was performed to assess EF. Kidney function was characterized by eGFR using the abbreviated Modification of Diet in Renal Disease formula. Linear regression was performed to assess the relationship between EF and kidney function in claudicants. Results 97 patients with intermittent claudication participated in this study. Mean age was 69 ± 8 years, 97% were male, and 77% were Caucasian. Comorbidities included hypertension (91%), dyslipidemia (87%), coronary artery disease (42%) and diabetes mellitus (38%). Mean ABI was 0.73 ± 0.14 and mean FMD was 7.0% ± 3.8, indicating impaired EF. Linear regression showed an association between kidney function and EF (by 10 ml/min/1.73m2, β: 0.12; CI: 0.05, 0.20; P = .001). After multivariable regression adjusting for age, race, log TNF-α, hypertension, dyslipidemia, and diabetes, eGFR remained significantly associated with EF (P = .033). Conclusions In patients with PAD, decreased kidney function is associated with endothelial dysfunction. Further longitudinal studies are needed to better understand the impact of kidney function on PAD progression and the role of endothelial dysfunction in this process.

Relationship Between Asymmetric Dimethylarginine (ADMA) and Atherosclerosis in Chronic Renal Failure Patients

“…Albuminuria leads to a reduction in the endothelium-dependent vascular relaxation response in glomerular endothelial cells [18]. Potential mediators between kidney function and endothelial function included ADMA and TNF-α [19]. Similar results were found by Recio-Mayoral et al [20] and Shukla et al [21] who observed that hemodialysis and CKD stage 4patients had reduced FMD values as compared to controls.…”

“…Similar results were found by Recio-Mayoral et al [20] and Shukla et al [21] who observed that hemodialysis and CKD stage 4patients had reduced FMD values as compared to controls. Chong et al [19] found an inverse relationship between renal function and FMD in symptomatic peripheral arterial disease.…”

One-Year Results of First-Line Treatment Strategies in Patients With Critical Limb Ischemia (CRITISCH Registry)

“…[24][25][26] Although CKD is an important determinant of cardiovascular morbidity and mortality, its role in PAD remains imprecisely defined. [26][27][28][29][30] Of note, in the BASIL trial the presence of ESRD was an exclusion criterion. 5 Patients with CKD and especially ESRD represent unique subgroups with special needs, and the treating physicians should be aware of the negative impact of CKD on the prognosis of CLI.…”

In‐hospital outcome of peripheral vascular intervention in dialysis‐dependent end‐stage renal disease patients

“…The most important risk factors for the development of PAD are similar to those for other atherosclerotic vascular diseases which include diabetes, smoking, hypetension, and hyperlipidemia . Impaired endothelial function and increased vascular calcification are other factors that may contribute to the development of PAD and adverse outcomes in ESRD patients . Kidney disease is known to produce a state of oxidative stress and inflammation, both of which are strong depressors of endothelial function.…”