Vitamin D metabolism and vitamin D traditional and nontraditional, target organs: implications for kidney patients

Vitamin D plays an absolute essential role in human physiology. More than 60 types of cells possess vitamin D receptors (VDR) and more than 200 genes represent the target for VDR activation. The principle of the biological effect of vitamin D is gene control. In general, VDR activation inhibits cell differentiation and proliferation while promoting cell maturation and it also participates in the regulation of apoptosis (programmed cell death). Conventionally, vitamin D status is assessed according to the serum 25-hydroxyvitamin D concentration. Values between 30-60 ng/ml (70-150 nmol/l) are optimal. Low vitamin D status is associated with bone and mineral disturbances and also with many other pathological conditions. Studies have described association with susceptibility to some infections; higher risk of autoimmune diseases, association with some malignancies and many other complications. Low vitamin D status is common, but usually underestimated. The native vitamin D undergoes two-step hydroxylation to become biologically active. The second metabolic conversion is dependent on functional renal parenchyma. In advanced stages of chronic kidney disease (CKD) the renal activation of vitamin D sharply decreases regardless of the stores of native vitamin D, resulting in low concentration of active vitamin D. The parathyroid hyperactivity in advanced CKD represents the approved indication for pharmacological VDR activation. The therapeutic window of nonselective VDR activators is narrow. On the contrary, the effect of selective VDR activators (paricalcitol) in the intestine is much lower and therefore the activators are safer in terms of maintaining serum concentration of calcium and phosphate. Several recent observational studies demonstrated survival benefits of selective VDR activation in CKD patients. Theoretically, these drugs may, at least, partly cover the need for the systemic activation of VDR in kidney patients, but this assumption must be carefully examined. At present, the possible cardioprotectivity, renoprotectivity and other benefits of selective VDR activators are being intensively studied.