Metabolic acidosis reverses the increase in serum 1,25(OH)2D in phosphorus-restricted normal men.
We tested the hypothesis that in humans, metabolic acidosis can disorder the metabolism of 1,25-dihydroxyvitamin D [1,25(OH)2D] by impairing the capacity for a sustained physiological stimulus to increase renal production of this hormone. Specifically, in seven healthy men in whom restriction of dietary phosphorus had doubled their serum concentration of 1,25(OH)2D, we induced metabolic acidosis of moderate severity with oral NH4Cl, administered for 7 days. With induction of acidosis, the serum concentration of 1,25(OH)2D decreased sharply and remained decreased and near constant throughout the period of acidosis, the decrease amounting to one-half of the increment induced by phosphorus restriction alone. The serum concentration of free 1,25(OH)2D also decreased, since the measured free fraction of 1,25(OH)2D was unaffected by NH4Cl. The decrease in serum 1,25(OH)2D was accounted for by a 16% increase in its metabolic clearance rate and by a 19% decrease in its production rate. Metabolic acidosis induced a modest increase in the concentrations of blood ionized calcium and serum phosphorus. Multiple linear regression analysis revealed that serum levels of 1,25(OH)2D varied inversely and significantly with those of plasma hydrogen ion (R = -0.77, P < 0.001), but not with those of blood ionized calcium or serum phosphorus. These data demonstrate in humans that metabolic acidosis can substantially reverse the increase in serum concentration of 1,25(OH)2D induced by phosphorus restriction. The data provide evidence that acidosis can restrict the increase in renal production and serum concentration of 1,25(OH)2D effected by a sustained physiological stimulus.
Portale
A A
AA
Department of Pediatrics, University of California, San Francisco.
Halloran
B P
BP
Harris
S T
ST
Bikle
D D
DD
Morris
R C
RC
D000136:Acid-Base Equilibrium; D000138:Acidosis / Q000097:blood* / Q000139:chemically induced; D000328:Adult; D000643:Ammonium Chloride; D001769:Blood / Q000378:metabolism; D002118:Calcium / Q000097:blood; D004100:Dihydroxycholecalciferols / Q000097:blood*; D006801:Humans; D008274:Magnesium / Q000097:blood; D008297:Male; D010758:Phosphorus / Q000097:blood / Q000172:deficiency*; D012016:Reference Values; D014556:Urine / Q000737:chemistry
D004100:Dihydroxycholecalciferols; D000643:Ammonium Chloride; D010758:Phosphorus; D008274:Magnesium; D002118:Calcium