Vitamin D metabolism in chronic renal failure

The great potency of 1,25 (OH)(2)D-3 in increasing intestinal calcium absorption and eventually serum calcium requires a strict regulation of vitamin D metabolism: 1,25(OH)(2)D-3 concentrations are several hundred times lower than those of 25(OH)(2)D-3 and normally are not affected by changes in precursor levels. This is obtained by the presence of a complex system of interrelated factors that affect the synthesis and degradation of 1,25(OH)(2)D-3. The most important regulators of calcitriol levels are PTH, serum phosphorus, serum ionized calcium, and 1,25(OH)(2)D-3 itself. Recent studies also suggest the presence of a new hormone, phosphatonin, which apparently inhibits the renal 1 alpha-hydroxylase and the renal phosphate transport. In advanced renal failure, the ability of the kidney to synthesize calcitriol is greatly reduced, and many patients are treated with active vitamin D metabolites. Vitamin D metabolism in dialysis patients could therefore be considered a secondary issue, but it has been shown that extrarenal synthesis of calcitriol takes place in uremia. Although 25(OH)D-3 levels are normal in uremia, uremic patients - after 25(OH)D-3 therapy - show a correlation between serum levels of 25(OH)D-3 and 1,25(OH)(2)D-3, which was confirmed in the absence of renal mass. The low basal levels of serum calcitriol in anephric patients suggest a minor contribution of extrarenal sources in the presence of physiological concentrations of 25(OH)D-3. However, these sources have the potential to normalize serum 1,25(OH)(2)D-3 when the concentration of substrate is raised to supranormal levels, indicating that substrate availability to extrarenal la-hydroxylase plays an important role in the contribution of extrarenal sources to systemic calcitriol concentrations in chronic uremia, It is now an accepted fact that 1,25(OH)(2)D-3 belongs in the family of steroid hormones. Indeed, its actions go far beyond the regulation of calcium-phosphate metabolism: the involvement of vitamin D in cell differentiation and proliferation is the most recent frontier added to the vitamin D endocrine system. The patient affected by chronic renal failure, both in the pre-dialysis period and when developing end stage renal failure, shows great abnormalities in vitamin D metabolism and will definitely benefit from further re-search aimed at defining the physiologic and physiopathologic mechanisms of vitamin D regulation.