Altered renal cellular
phosphate (Pi) homeostasis may be involved in disturbed regulation of 1 alpha, 25-dihydroxyvitamin D3 [
1,25(OH)2D3] production in
chronic renal failure. To assess cytoplasmic concentrations of P(i) and other
phosphate metabolites in
uremia,
phosphorus-magnetic resonance spectroscopy (31P-MRS) studies were carried out in vivo in rat remnant kidney. Five-sixths-nephrectomized animals (Nx, n = 8, serum
creatinine 1.28 +/- 0.18 mg/ dl) and
sham-operated control animals (n = 8) were pair-fed a high-
phosphate diet (1.6%
phosphate, 1.0%
calcium) for 19 days. In both remnant and intact kidneys, 31P-magnetic resonance spectra displayed six major peaks: phosphomonoesters (PME), P(i), phosphodiesters, and
adenosine triphosphate (
ATP)-gamma, -alpha, and -beta.
Phosphocreatine was absent. The relative intensity of the renal gamma
ATP signal was comparable between the remnant kidney in Nx and the
sham-operated kidney in control animals and was, therefore, used as the internal standard to assess the P(i)/gamma
ATP ratio. The P(i)/gamma
ATP ratio was significantly (p < 0.05) increased in the remnant kidney as compared to the
sham-operated control kidney (0.97 +/- 0.24 in Nx vs. 0.75 +/- 0.12 in
sham-operated controls; means +/- SE). Similarly, the PME/gamma
ATP ratio was significantly increased in Nx (p < 0.01), whereas the relative intensities of other
phosphate metabolite signals were not altered in Nx. Mean serum
1,25(OH)2D3 concentrations were 62 pg/ml for Nx and 93 for
sham-operated controls (p < 0.05); mean serum
phosphate levels were 4.35 mmol/l for Nx and 2.61 for
sham-operated controls (p < 0.01). The pH in the remnant kidneys was 7.20 +/- 0.06 (mean +/- SE, n = 8), whereas the pH in intact kidneys was 7.29 +/- 0.05 (n = 8, p < 0.05). To examine the contribution of blood cells to 31P-magnetic resonance spectra, an exchange transfusion with a fluorocarbonated
oxygen carrier (to a final hematocrit of 8%) was carried out, while animals (n = 5) were monitored by MRS. This did not significantly change the relative intensities of
phosphate metabolite peaks, indicating that blood
phosphorus did not measurably contribute to the renal P(i) signal. The data suggest that intrarenal P(i) concentration is elevated in
renal failure. This could inhibit 25-hydroxyvitamin D3-1 alpha-
hydroxylase activity and thus have some relevance for pathogenesis of renal
hyperparathyroidism.