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Renal adaptation to phosphate deprivation: lessons from the X-linkedHyp mouse

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Abstract

The X-linkedHyp 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 mutantHyp mice differs from that of normal littermates. WhileHyp mice fed a low phosphate diet retain the capacity to exhibit a significant increase in renal brush-border membrane sodiumphosphate 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 inHyp mice is also apparent in X-linkedGy 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.

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  1. MRC Genetics Group, Department of Pediatrics, Centre for Human Genetics, Department of Biology, McGill University-Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada

    Harriet S. Tenenhouse & Josée Martel

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  1. Harriet S. Tenenhouse
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Tenenhouse, H.S., Martel, J. Renal adaptation to phosphate deprivation: lessons from the X-linkedHyp mouse. Pediatr Nephrol 7, 312–318 (1993). https://doi.org/10.1007/BF00853232

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