Modulation of vitamin D signaling is a potential therapeutic target to lower cardiovascular risk in chronic kidney disease

While it is true that many traditional cardiovascular risk factors are amenable to intervention in chronic kidney disease (CKD), the results of intervention may not be as efficacious as those obtained in the general population. Thus, there may also be a unique milieu established in CKD, which causes excess cardiovascular disease (CVD) burden by mechanisms that are as yet not fully recognized. Recently, vitamin D has sparked widespread interest because of its potential favorable benefits on CVD. However, the mechanisms for how vitamin D may improve CVD risk markers and outcomes have not been fully elucidated. Furthermore, hypovitaminosis D is highly prevalent in the CKD cohort. Given this background, we hypothesize that low vitamin D status may act as a new CVD risk marker, and modulation of vitamin D signaling may be a potential therapeutic target to lower cardiovascular risk in CKD. The data presented in this review support that the low vitamin D status may be linked with the high cardiovascular risk in CKD, based on both the biological effects of vitamin D itself on the cardiovascular system, and the cross-actions between vitamin D signaling and the multiple metabolic pathways. Considering the high prevalence of hypovitaminosis D, limited natural vitamin D food sources, and reduced sun exposure in CKD patients, recommendations for treatment of hypovitaminosis D mainly focus on exogenous supplementation with vitamin D and its analogues. Although promising, when to start therapy, the route of administration, the dose, and the duration remain need to be discussed.