Maleic acid-induced impaired conversion of 25(OH)D3 to 1,25(OH)2D3: implications for Fanconi's syndrome.
Conversion of 25-hydroxyvitamin D3 [25(OH)D3] to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] occurs exclusively in the renal cortex. To determine whether a disorder of the renal cortical tubule capable of causing Fanconi's syndrome can also impair the synthesis of 1,25(OH)2D3, we investigated whether conversion of 25(OH)D3 to 1,25(OH)2D3 was reduced by maleic acid. In vitamin D-deficient rats, maleic acid was administered i.v. over two hours. Thirty minutes after its initiation, when the complex renal tubule dysfunction had occurred, 3H-25(OH)D3 was administered i.v. as a bolus. Five hours afterwards, the amount of 3H-1,25(OH)2D3 recovered in the kidney, small intestine mucosa, and blood was one-third to one-half that in tissues of control rats that received acetazolamide or only saline or were subjected only to the surgical procedure. The glomerular filtration rate, as measured by inulin clearance, did not decrease significantly with maleic acid. In intact vitamin D-deficient chicks, 24 and 22 hr after i.p. administration of maleic acid and 14C-vitamin D3, respectively, the amount of 14C-1,25(OH)2D3 recovered in small intestine mucosa was reduced by one-half when compared to saline-treated controls. In kidney homogenates and isolated renal tubules of vitamin D-deficient chicks, activity of 25-hydroxyvitamin D3-1-hydroxylase was diminished immediately after maleic acid was administered in vivo or added in vitro to the incubation medium, respectively. These data provide the first demonstration that the renal capacity to convert 25(OH)D3 to 1,25(OH)2D3 can be substantially impaired in vivo by a renal disorder in which the glomerular filtration rate is not reduced.
D000086:Acetazolamide / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D004100:Dihydroxycholecalciferols / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D005198:Fanconi Syndrome / Q000209:etiology* / Q000378:metabolism; D005919:Glomerular Filtration Rate; D006887:Hydroxycholecalciferols / Q000096:biosynthesis* / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D008298:Maleates / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D008298:Maleates; D000086:Acetazolamide