EFFECT OF VITAMIN-D METABOLITES ON CALCITRIOL DEGRADATIVE ENZYMES IN RENAL-FAILURE

We have demonstrated that in renal failure calcitriol degradation is d ecreased and that administration of vitamin D metabolites increases th e degradation. In this study, we measured intestinal 24- and 26-hydrox ylase activities and the effects of chronic infusion (7 days) of vitam in D metabolites on these enzymes' activities in rats with experimenta l 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 n g/day) significantly increased 24-hydroxylase activity by 17% in rats with renal failure (P < 0.01), although the activity remained 15% lowe r than the controls (P < 0.01). Intestinal 26-hydroxylase activity was not lower in renal failure; however, calcitriol treatment increased t he activity beyond that of normal controls. In contrast, administratio n of 25(OH)D3 (600 ng/day) and 24,25(OH)2D3 (1 mug/day) reduced the co nversion 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 enzym atic activities of both 24- and 26-hydroxylase. However, the mechanism s of increased calcitriol degradation by 25(OH)D3 and 24,25(OH)2D3 in renal failure remain unknown.