Renal adaptation to phosphate deprivation: lessons from the X-linked Hyp mouse.
The X-linked Hyp mutation, a murine homologue of X-linked hypophosphatemia in humans, is characterized by renal defects in phosphate reabsorption and vitamin D metabolism. In addition, the renal adaptive response to phosphate deprivation in mutant Hyp mice differs from that of normal littermates. While Hyp mice fed a low phosphate diet retain the capacity to exhibit a significant increase in renal brush-border membrane sodium-phosphate cotransport in vitro, the mutants fail to show an adaptive increase in maximal tubular reabsorption of phosphate per volume of glomerular filtrate (TmP/GFR) in vivo. Moreover, unlike their normal counterparts, Hyp mice respond to phosphate restriction with a fall in the serum concentration of 1,25-dihydroxyvitamin D [1,25(OH)2D] that can be ascribed to increased renal 1,25(OH)2D catabolism. The dissociation between the adaptive brush-border membrane phosphate transport response and the TmP/GFR and vitamin D responses observed in Hyp mice is also apparent in X-linked Gy mice and hypophysectomized rats. Based on these findings and the notion that transport across the brush-border membrane reflects proximal tubular function, we suggest that the adaptive TmP/GFR response requires the participation of 1,25(OH)2D or a related metabolite and that a more distal segment of the nephron is the likely target for the 1,25(OH)2D-dependent increase in overall tubular phosphate conservation.
Department of Pediatrics, McGill University-Montreal Children's Hospital Research Institute, Quebec, Canada.
H S
HS
Tenenhouse
J
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Martel
D000222:Adaptation, Physiological; D000818:Animals; D004195:Disease Models, Animal; D008040:Genetic Linkage; D007014:Hypophosphatasia / Q000235:genetics* / Q000503:physiopathology*; D007668:Kidney / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D014807:Vitamin D / Q000378:metabolism; D014960:X Chromosome
D010710:Phosphates; D014807:Vitamin D