It has been demonstrated that many chains in the vitamin D pathway are affected by uremia. Uremic solute retention is responsible for changes in calcitriol production, resulting in a net decrease of blood calcitriol levels. This effect contributes to the calcitriol deficiency currently observed in renal failure. Next to the altered production and metabolization of calcitriol, altered expression of the vitamin D receptor (VDR) and altered binding properties of the hormone receptor complex to the DNA could also contribute to the relative status of calcitriol resistance in renal failure. These alterations could finally result in an impairment of the end biological action of calcitriol.