Abstract
The cardiorenal syndrome relates to the detrimental interplay between the vascular system and the kidney. The uremic milieu induced by reduced kidney function alters the phenotype of vascular smooth muscle cells (VSMC) and promotes vascular calcification, a condition which is strongly linked to cardiovascular morbidity and mortality. Biological mechanisms involved include generation of reactive oxygen species, inflammation and accelerated senescence. A better understanding of the vasotoxic effects of uremic retention molecules may reveal novel avenues to reduce vascular calcification in CKD. The present review aims to present a state of the art on the role of uremic toxins in pathogenesis of vascular calcification. Evidence, so far, is fragmentary and limited with only a few uremic toxins being investigated, often by a single group of investigators. Experimental heterogeneity furthermore hampers comparison. There is a clear need for a concerted action harmonizing and standardizing experimental protocols and combining efforts of basic and clinical researchers to solve the complex puzzle of uremic vascular calcification.
Highlights
The cardiorenal syndrome relates to the detrimental interplay between the vascular system and the kidney
We present a state of the art on the effects of uremic retention molecules on vascular smooth muscle cells (VSMC) with relevance for early vascular ageing (EVA) and vascular calcification (VC) related cardiovascular disease (CVD)
VC as consequence of EVA can occur at two distinct sites: in the intimal layer of vessels where it is associated with atherosclerosis and in the medial layer, where it is referred to as Mönckeberg sclerosis
Summary
Chronic kidney disease (CKD) is recognized as a major non-communicable disease of growing epidemic dimension worldwide. The risk for cardiovascular disease (CVD) related hospitalization or death has been shown to increase with progression of CKD [5]. CRS type 4, the chronic renocardiac syndrome, describes CKD leading to CVD [7]. While traditional Framingham risk factors like dyslipidaemia and diabetes contribute to CVD, they cannot fully explain the excessive mortality observed in patients with CRS type 4. Non-traditional risk factors including inflammation, oxidative stress or abnormal calcium-phosphate metabolism, have been found to account, at least partly, for the excessively high cardiovascular morbidity and mortality in these patients [8]. VC affects up to 60% of CKD patients and is even more prevalent in dialysis patients [11] It has been independently associated with CV morbidity and mortality [11,12]. In depth analysis of translational cohort studies investigating extreme EVA, such as CKD, provides valuable insights in factors that drive vascular ageing, and which may be present in the older general population but take considerable longer time to evolve
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