Crosstransplantation of kidneys in normal and Hyp mice. Evidence that the Hyp mouse phenotype is unrelated to an intrinsic renal defect.
Although deranged phosphate transport is the fundamental abnormality in X-linked hypophosphatemic (XLH) rickets, it remains unknown if this defect is the consequence of an intrinsic kidney abnormality or aberrant production of a humoral factor. To discriminate between these possibilities, we examined phosphate homeostasis in normal and Hyp mice, subjected to renal crosstransplantation. We initially evaluated the effects of uninephrectomy on the indices of phosphate metabolism that identify the mutant biochemical phenotype. No differences were found in the serum phosphorus concentration, fractional excretion of phosphate (FEP), or tubular reabsorption of phosphate per milliliter of glomerular filtrate (TRP) in uninephrectomized normal and Hyp mice, compared with sham-operated controls. Subsequently, single kidneys from normal or Hyp mice were transplanted into normal and Hyp mouse recipients. Normal mice transplanted with normal kidneys and Hyp mice engrafted with mutant kidneys exhibited serum phosphorus, FEP, and TRP no different from those of uninephrectomized normal and Hyp mice, respectively. However, engraftment of normal kidneys in Hyp mice and mutant kidneys in normal mice affected neither serum phosphorus (4.69 +/- 0.31 and 8.25 +/- 0.52 mg/dl, respectively) nor FEP and TRP of the recipients. These data indicate that the Hyp mouse phenotype is neither corrected nor transferred by renal transplantation. Further, they suggest that the phosphate transport defect in Hyp mice, and likely X-linked hypophosphatemia, is the result of a humoral factor, and is not an intrinsic renal abnormality.
Nesbitt
T
T
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Coffman
T M
TM
Griffiths
R
R
Drezner
M K
MK
D000818:Animals; D005919:Glomerular Filtration Rate; D006706:Homeostasis; D007015:Hypophosphatemia, Familial / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D016030:Kidney Transplantation; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D010710:Phosphates / Q000378:metabolism; D014960:X Chromosome
D010710:Phosphates