Renal 31-phosphorus-magnetic resonance spectral changes in experimental uremia

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.