Vitamin D metabolism in chronic renal failure

The great potency of 1,25 (OH)2D3 in increasing intestinal calcium absorption and eventually serum calcium requires a strict regulation of vitamin D metabolism: 1,25(OH)2D3 concentrations are several hundred times lower than those of 25(OH)2D3 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)2D3. The most important regulators of calcitriol levels are PTH, serum phosphorus, serum ionized calcium, and 1,25(OH)2D3 itself. Recent studies also suggest the presence of a new hormone, phosphatonin, which apparently inhibits the renal 1\u3b1-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)D3 levels are normal in uremia, uremic patients - after 25(OH)D3 therapy - show a correlation between serum levels of 25(OH)D3 and 1,25(OH)2D3, 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)D3. However, these sources have the potential to normalize serum 1,25(OH)2D3 when the concentration of substrate is raised to supranormal levels, indicating that substrate availability to extrarenal 1\u3b1-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)2D3 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 research aimed at defining the physiologic and physiopathologic mechanisms of vitamin D regulation