Chronic Kidney Disease

Abstract

Abstract-Accelerated cardiovascular disease is a frequent complication of renal disease. Chronic kidney disease promotes hypertension and dyslipidemia, which in turn can contribute to the progression of renal failure. Furthermore, diabetic nephropathy is the leading cause of renal failure in developed countries. Together, hypertension, dyslipidemia, and diabetes are major risk factors for the development of endothelial dysfunction and progression of atherosclerosis. Inflammatory mediators are often elevated and the renin-angiotensin system is frequently activated in chronic kidney disease, which likely contributes through enhanced production of reactive oxygen species to the accelerated atherosclerosis observed in chronic kidney disease. Promoters of calcification are increased and inhibitors of calcification are reduced, which favors metastatic vascular calcification, an important participant in vascular injury associated with end-stage renal disease. Accelerated atherosclerosis will then lead to increased prevalence of coronary artery disease, heart failure, stroke, and peripheral arterial disease. Consequently, subjects with chronic renal failure are exposed to increased morbidity and mortality as a result of cardiovascular events. Prevention and treatment of cardiovascular disease are major considerations in the management of individuals with chronic kidney disease. Key Words: atherosclerosis Ⅲ hypertension Ⅲ kidney Ⅲ vasculature I t is increasingly apparent that individuals with chronic kidney disease (CKD) are more likely to die of cardiovascular (CV) disease (CVD) than to develop kidney failure. 1,2 A large cohort study comprising Ͼ130 000 elderly subjects showed that increased incidence of CV events could be in part related to the fact that persons with renal insufficiency are less likely to receive appropriate cardioprotective treatments. 3 However, beyond the effects of lack of appropriate therapy, it is clear that accelerated CVD is prevalent in subjects with CKD. The first part of the present review will therefore focus on the epidemiological links between impairment of renal function and adverse CV events, between albuminuria and CV events, and between serum cystatin C and CVD. The second part of the present review will address the mechanisms that lead to the association of renal and CVD, which include hypertension, dyslipidemia, activation of the renin-angiotensin system, endothelial dysfunction and the role of asymmetric dimethyl arginine (ADMA), oxidative stress, and inflammation. Finally, mechanisms that are involved in vascular calcification often found in CKD and end-stage renal disease (ESRD) will be described. Additionally, ESRD is associated with several specific complications caused by the uremic state per se, which can contribute to the development and progression of CVD through volume overload with consequent hypertension, anemia, uremic pericarditis, and cardiomyopathy. However, these issues will not be addressed because the emphasis will be on CKD before ESRD is reached. In addition, t...

Reduced blood pressure after smooth muscle EFNB2 deletion and the potential association of EFNB2 mutation with human hypertension risk

“…Considering the conservative nature of Bonferroni correction, and the high LD link of rs7328882 with the other four SNPs, it is reasonable to assume that the functional mutation related to this LD block is still significantly associated with hypertension even after CKD was used a covariate. (2) Although CKD could cause hypertension, 45 the reverse is also true, ie, hypertension frequently leads to the development of CKD. 46 In our case, the introduction of CKD as a covariate in the statistical analysis reduces somewhat significance of the association between some EFNB2 SNPs and hypertension, but this does not necessarily mean that CKD is causative for the hypertension.…”

Reduced Kidney Function Is Associated With Cardiometabolic Risk Factors, Prevalent and Predicted Risk of Cardiovascular Disease in Chinese Adults: Results From the REACTION Study

“…Atherosclerosis could be another important factor linking impaired kidney function and the risk of incident CVD. Elevated asymmetric dimethyl arginine, reduced nitric oxide bioavailability, and endothelial dysfunction in renal disease, which are associated with atherosclerosis, could also contribute to incident CVD 27, 28. Experimental studies suggest that the renin‐angiotensin system (RAS) and its primary effector peptide, angiotensin II, are involved in the pathophysiology of cardiac hypertrophy and failure 29, 30.…”

Extracellular Fluid Excess Is Significantly Associated With Coronary Artery Calcification in Patients With Chronic Kidney Disease

“…The increased incidence of cardiovascular events in patients with CKD is related to both traditional and nontraditional cardiovascular risk factors 2. Nontraditional cardiovascular risk factors include uremia‐related factors, inflammation, and abnormal metabolism of calcium and phosphate 3, 4…”