The vitamin D system: a crosstalk between the heart and kidney.
Chronic kidney disease (CKD) independently increases the rates of cardiovascular disease, whereas the severity of kidney disease correlates with increased cardiovascular morbidity and death. Vitamin D is modified in the liver and the kidney to its active form (1,25-dihydroxyvitamin D) by the 25-hydroxy vitamin D 1-hydroxylase enzyme (CYP27B1). The activated vitamin D brings about its actions through the vitamin D receptor (VDR). The VDRs and CYP27B1 have recently been shown to be expressed in several tissues, not directly involved in mineral homeostasis, including the cardiovascular, immune, and epithelial systems. The action of vitamin D in these tissues is implicated in the regulation of endothelial, vascular smooth muscle, and cardiac cell function, the renin-angiotensin system, inflammatory and fibrotic pathways, and immune response. Impaired VDR activation and signalling results in cellular dysfunction in several organs and biological systems, which leads to reduced bone health, an increased risk for epithelial cancers, metabolic disease, and uncontrolled inflammatory responses. Failure of cardiovascular VDR activation results in hypertension, accelerated atherosclerosis and vascular calcification, cardiac hypertrophy with vascular rarification and fibrosis, and progressive renal dysfunction. An emerging body of evidence has prompted attention to the relationship between CKD, mineral bone disorder (CKD-MBD), and cardiovascular disease in the new guidelines from Kidney Disease: Improving Global Outcomes. Vitamin D receptor activators, commonly used to treat CKD-MBD, and an appropriate treatment of vitamin D hormonal system failure in patients with CKD, may help to reduce cardiovascular morbidity and mortality in these patients.
Cozzolino
Mario
M
Renal Division, S. Paolo Hospital, University of Milan, Via A. di Rudin'ı, 8-20142 Milan, Italy. mariocozzolino@hotmail.com
Ketteler
Markus
M
Zehnder
Daniel
D
D016001:Confidence Intervals; D005919:Glomerular Filtration Rate; D006321:Heart / Q000502:physiology*; D006331:Heart Diseases / Q000401:mortality / Q000503:physiopathology*; D006801:Humans; D017379:Hypertrophy, Left Ventricular; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000502:physiology*; D007674:Kidney Diseases / Q000401:mortality / Q000503:physiopathology*; D015999:Multivariate Analysis; D012307:Risk Factors; D014807:Vitamin D / Q000502:physiology*
D014807:Vitamin D