Endothelial dysfunction and cardiovascular disease in early-stage chronic kidney disease: Cause or association?

Cardiovascular and Respiratory Sciences, School of Clinical & Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, UK.
Atherosclerosis (Impact Factor: 3.99). 02/2012; 223(1):86-94. DOI: 10.1016/j.atherosclerosis.2012.01.043
Source: PubMed


Chronic kidney disease (CKD) is strongly associated with cardiovascular disease (CVD); a graded inverse relationship between estimated glomerular filtration rate (eGFR) and cardiovascular event rates has emerged from large-scale observational studies. Chronic kidney disease is also associated with endothelial dysfunction (ED) although the precise relationship with GFR and the "threshold" at which ED begins are contentious. Abnormal endothelial function is certainly present in late-stage CKD but data in early-stage CKD appear confounded by disease states such as diabetes and hypertension which themselves promote ED. Thus, the direct effect of a reduction in GFR on endothelial function and, therefore, cardiovascular (CV) risk is far from completely established. In human studies, the precise duration of kidney impairment is seldom known and the onset of CVD often insidious, making it difficult to determine exactly when CVD first appears in the context of CKD. Kidney donors provide a near-ideal experimental model of CKD; subjects undergo an acute change from normal to modestly impaired renal function at the time of nephrectomy and lack the confounding co-morbidity that has made observational studies of CKD patients so challenging to interpret. By examining changes in endothelial function in living kidney donors before and after nephrectomy, useful insight might be gained into the pathophysiology of CVD in CKD and help determine whether targeting ED or the renal disease itself has the potential to reduce CV risk.

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    • "In addition to the conventional CV risk factors (that is, hypertension, hypercholesterolaemia and smoking), other risk factors including activation of the renin-angiotensin-aldosterone system (RAAS), increased oxidative stress or inflammation, proteinuria and mineral bone disorder are also believed to be vital in contributing to the high CV burden in the CKD population [14,15]. Cardiovascular disease in CKD differs from that of the general population [14,15]. "
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