Vitamin D receptor polymorphism in chronic kidney disease patients with complicated cardiovascular disease.

Several studies indicate a relationship between vitamin D and cardiovascular disease. Pleiotropic actions of vitamin D and its analogs are mediated by vitamin D receptor (VDR). VDRs have been identified in almost all tissues, including vascular smooth muscle cells, cardiomyocytes, and endothelial cells. The FokI and BsmI polymorphisms of the VDR gene are regarded as strong markers of disturbed vitamin D signaling pathway. Studies investigating the relationship between VDR genotypes and left ventricular hypertrophy revealed a highly significant association with the BsmI Bb heterozygous genotype. There are conflicting data on the action of vitamin D in left ventricular hypertrophy. Experimental as well as observational studies and small clinical trials have suggested that vitamin D administration may favorably influence left ventricular hypertrophy, whereas large randomized clinical trials have shown negative results. However, a beneficial effect on the left atrial volume index and the duration of hospitalization were observed in patients treated with vitamin D analogs. Larger clinical trials with robust clinical end points are needed to confirm that vitamin D is effective in preventing cardiovascular disease in chronic kidney disease patients and in general population.

Vitamin D receptor gene polymorphism and left ventricular hypertrophy in chronic kidney disease.

FokI and BsmI polymorphisms of vitamin D receptor (VDR) gene are regarded as reliable markers of disturbed vitamin D signaling pathway. Left ventricular hypertrophy (LVH) is a strong cardiovascular risk marker in end stage renal disease (ESRD) patients. Since BsmI polymorphism has been associated with LVH in ESRD patients, we addressed this study in patients with chronic kidney disease (CKD) not yet on dialysis. One hundred and forty five patients with CKD stage 3 were genotyped for FokI and BsmI VDR polymorphisms, in order to assess the relationships between these VDR polymorphisms, some markers of mineral bone disorders, and LVH measured by echocardiography. Patients bearing either the Ff heterozygous or FF homozygous genotype had significantly higher PTH values than those bearing the ff genotype. The relationships between VDR genotypes and LVH revealed a highly significant association of the BsmI Bb heterozygous genotype with LVH. In patients with CKD stage 3 BsmI B allele was independently related to LVH. Since LVH is a frequent finding in dialysis population due to several mechanisms, the presence of the same relationship in patients with CKD strengthens the hypothesis that alterations of vitamin D signaling are implicated in LVH development in patients with renal diseases.

Vitamin D metabolism and activity as well as genetic variants of the vitamin D receptor (VDR) in chronic kidney disease patients.

For a long time, the role of vitamin D in chronic kidney disease (CKD) received less attention than treating vitamin D metabolism disorders. Low active vitamin D levels represent one of the most important factors in the pathophysiology of secondary hyperparathyroidism. For this reason, the administration of active vitamin D compounds is commenced during the course of CKD treatment. Moreover, patients with CKD exhibit a high prevalence of hypovitaminosis of 25-hydroxyvitamin D (25[OH]D) unrelated to vitamin D intake. However, several studies have recently advanced our knowledge about the effects of both the 25(OH)D and 1,25(OH)2D forms of endogenous vitamin D and the possible beneficial effects of vitamin D treatment. These studies add to the already well-known effects of vitamin D on mineral metabolism. Several studies have hypothesized a link between reduced levels of 25-OH D and a greater cardiovascular risk in the general population. Another important aspect of vitamin D metabolism is the existence of polymorphic genetic variants of the vitamin D receptors (VDRs). Most studies have aimed to determine whether VDR polymorphisms are involved in the development of secondary hyperparathyroidism (sHPT).