Atherosclerosis in Chronic Kidney Disease

Abstract

Patients with chronic kidney disease (CKD) are at an increased risk of premature mortality, mainly from cardiovascular causes. The association between CKD on hemodialysis and accelerated atherosclerosis was described >40 years ago. However, more recently, it has been suggested that the increase in atherosclerosis risk is actually observed in early CKD stages, remaining stable thereafter. In this regard, interventions targeting the pathogenesis of atherosclerosis, such as statins, successful in the general population, have failed to benefit patients with very advanced CKD. This raises the issue of the relative contribution of atherosclerosis versus other forms of cardiovascular injury such as arteriosclerosis or myocardial injury to the increased cardiovascular risk in CKD. In this review, the pathophysiogical contributors to atherosclerosis in CKD that are shared with the general population, or specific to CKD, are discussed. The NEFRONA study (Observatorio Nacional de Atherosclerosis en NEFrologia) prospectively assessed the prevalence and progression of subclinical atherosclerosis (plaque in vascular ultrasound), confirming an increased prevalence of atherosclerosis in patients with moderate CKD. However, the adjusted odds ratio for subclinical atherosclerosis increased with CKD stage, suggesting a contribution of CKD itself to subclinical atherosclerosis. Progression of atherosclerosis was closely related to CKD progression as well as to the baseline presence of atheroma plaque, and to higher phosphate, uric acid, and ferritin and lower 25(OH) vitamin D levels. These insights may help design future clinical trials of stratified personalized medicine targeting atherosclerosis in patients with CKD. Future primary prevention trials should enroll patients with evidence of subclinical atherosclerosis and should provide a comprehensive control of all known risk factors in addition to testing any additional intervention or placebo.

Should We Consider the Cardiovascular System While Evaluating CKD-MBD?

“…It is suggested that fluid overload and increased arterial stiffness play a role in LVH even before the start of dialysis therapy [15]. Arteriosclerosis, being a hallmark of arterial remodeling in ESRD, is characterized by diffuse calcification in combination with dilatation, and an increased wall thickness of the medial layer of the aorta and its main branches which drives increased arterial stiffness [11,16,17]. Here, LVH happens regardless of the effective control of hypertension.…”

Pathophysiological and Genetic Aspects of Vascular Calcification

“…Recent evidence shows that there is a high prevalence of vascular calcification (VC) in atherosclerosis, diabetes, and chronic kidney disease, standing out as an independent CRF of morbidity and mortality [2,3]. Data from the MESA study show that the calcium score (CAC), the main marker of CV, was associated with a gradual increase in risk events.…”

<p>Factors Associated with the Change in Carotid Maximum Intima-Media Thickness in Patients with Moderate-to-Advanced Stage Chronic Kidney Disease</p>

“…1 Various factors including uremic toxins, oxidative stress, diabetes mellitus, hypertension, and dyslipidemia have been considered to be responsible for progression of atherosclerosis in CKD patients. 2 Atherosclerosis contributes to the development of cardiovascular diseases including coronary artery disease and stroke, which are common causes of death in CKD patients. 3 Therefore, assessment of subclinical atherosclerosis is important for preventing the development and progression of cardiovascular disease.…”