Nephrol Dial Transplant. 2019 Apr 8. pii: gfz055.
Most exposed: the endothelium in chronic kidney disease. Vila Cuenca M1, Hordijk PL2, Vervloet MG1. Author information 1Department of Nephrology, Amsterdam Cardiovascular Sciences, VU University Medical Center, Amsterdam, The Netherlands.2Department of Physiology, Amsterdam Cardiovascular Sciences, VU University Medical Center, Amsterdam, The Netherlands. Abstract Accumulating evidence indicates that the pathological changes of the endothelium may contribute to the development of cardiovascular complications in chronic kidney disease (CKD). Non-traditional risk factors related to CKD are associated with the incidence of cardiovascular disease, but their role in uraemic endothelial dysfunction has often been disregarded. In this context, soluble α-Klotho and vitamin D are of importance to maintain endothelial integrity, but their concentrations decline in CKD, thereby contributing to the dysfunction of the endotheliallining. These hormonal disturbances are accompanied by an increment of circulating fibroblast growth factor-23 and phosphate, both exacerbating endothelial toxicities. Furthermore, impaired renal function leads to an increment of inflammatory mediators, reactive oxygen species and uraemic toxins that further aggravate the endothelial abnormalities and in turn also inhibit the regeneration of disrupted endothelial lining. Here, we highlight the distinct endothelial alterations mediated by the abovementioned non-traditional risk factors as demonstrated in experimental studies and connect these to pathological changes in CKD patients, which are driven by endothelialdisturbances, other than atherosclerosis. In addition, we describe therapeutic strategies that may promote restoration of endothelialabnormalities by modulating imbalanced mineral homoeostasis and attenuate the impact of uraemic retention molecules, inflammatory mediators and reactive oxygen species. A clinical perspective on endothelial dysfunction in CKD may translate into reduced structural and functional abnormalities of the vessel wall in CKD, and ultimately improved cardiovascular disease. © The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. KEYWORDS: CKD; cardiovascular; endothelial dysfunction; mineral metabolism; uraemic toxins