title: Abnormal tubular adaptation to dietary Pi restriction in X-linked hypophosphatemic mice.
abstract: The renal handling of inorganic phosphate (Pi) is in part under the control of a powerful mechanism that is independent of parathyroid hormone and has the ability to enhance net tubular Pi reabsorption in response to a reduction in the Pi supply. The decreased renal reabsorption of Pi, the salient feature of the human disease X-linked hypophosphatemia, could be due to a loss of this adaptive capability of the tubular Pi transport system. To investigate this hypothesis, mutant hypophosphatemic (HYP) mice were used as a model of the human disease. Male HYP mice and normal littermates were subjected to high (0.75 g/100 g), low (0.25 g/100 g), or very low (0.03 g/100 g) phosphorus diets for periods varying between 1 and 20 days. Then the overall tubular Pi transport capacity was assessed by determining the maximal net Pi reabsorption per unit volume of glomerular filtrate (max TRPi/ml GF). The results indicate that the marked enhancement of max TRPi/ml GF, which is observed in normal mice after the first day of Pi restriction, is completely absent in HYP mice. In chronically thyroparathyroidectomized animals, 10 days of low phosphorus diet stimulated conspicuous max TRPi/ml GF in normal mice, whereas the same regimen did not significantly change the Pi reabsorptive capacity of HYP counterparts. The results of this study suggest that X-linked hypophosphatemia is a disease with a defect in the mechanism responsible for the adaptation of the tubular Pi transport system to Pi restriction.
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000494:pharmacology; D004032:Diet; D005260:Female; D005919:Glomerular Filtration Rate; D006579:Heterozygote; D007015:Hypophosphatemia, Familial / Q000503:physiopathology*; D007684:Kidney Tubules / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010280:Parathyroid Glands / Q000503:physiopathology; D010710:Phosphates / Q000378:metabolism*; D012730:Sex Chromosomes; D013965:Thyroidectomy; D014960:X Chromosome
chemical_list: D010710:Phosphates; D002117:Calcitriol