The development of a
vitamin D-resistant state in the course of
renal failure may be responsible for reduced intestinal absorption of
calcium and an impaired response of skeletal tissue. Moreover, the kidney has been shown to carry out the conversion of
25-hydroxycholecalciferol (25-OH-CC) to a highly biologically active metabolite,
1,25-dihydroxycholecalciferol (1,25-diOH-CC). In the present studies,
vitamin D-deficient rats, made acutely uremic by either bilateral
nephrectomy or urethral
ligation, received physiological doses of
cholecalciferol (
vitamin D(3)) (CC), 25-OH-CC or 1,25-diOH-CC; 24 hr later intestinal
calcium transport, in vitro, and bone
calcium mobilization, in vivo, were assessed. Whereas CC and 25-OH-CC stimulated
calcium transport in
sham-operated controls, they were without effect in the uremic animals. In contrast, administration of 1,25-diOH-CC stimulated
calcium transport in both groups of uremic animals. Administration of 1,25-diOH-CC also stimulated
calcium mobilization from bone in each group of animals. However, CC and 25-OH-CC were only effective in the
sham controls and the uremic group produced by urethral
ligation and had little or no effect in animals without kidneys. These results indicate that renal conversion of calciferol to a more biologically active form is necessary for the stimulation of intestinal
calcium absorption and
calcium mobilization from bone, and that 1,25-diOH-CC may bypass a possible defect in
vitamin D metabolism in
uremia. From these studies it is likely that
uremia, per se, may also impair intestinal
calcium transport.