Effect of vitamin D metabolites on calcitriol degradative enzymes in renal failure

Abstract

We have demonstrated that in renal failure calcitriol degradation is decreased and that administration of vitamin D metabolites increases the degradation. In this study, we measured intestinal 24- and 26-hydroxylase activities and the effects of chronic infusion (7 days) of vitamin D metabolites on these enzymes' activities in rats with experimental renal failure. The enzymatic activity of intestinal 24-hydroxylase, but not 26-hydroxylase, was significantly lower in renal failure rats compared to control sham operated rats. Replacement of calcitriol (3 ng/day) significantly increased 24-hydroxylase activity by 17% in rats with renal failure (P < 0.01), although the activity remained 15% lower than the controls (P < 0.01). Intestinal 26-hydroxylase activity was not lower in renal failure; however, calcitriol treatment increased the activity beyond that of normal controls. In contrast, administration of 25(OH)D3 (600 ng/day) and 24,25(OH)2D3 (1 microgram/day) reduced the conversion of calcitriol to 1,24,25(OH)3D3 by more than 50% and to 1,25,26(OH)3D3 by more than 38%, respectively. We conclude that calcitriol increased its own degradation in renal failure by increasing the enzymatic activities of both 24- and 26-hydroxylase. However, the mechanisms of increased calcitriol degradation by 25(OH)D3 and 24,25(OH)2D3 in renal failure remain unknown.