Renal 31-Phosphorus-Magnetic Resonance Spectral Changes in Experimental Uremia

Abstract

Altered renal cellular phosphate (P_i) homeostasis may be involved in disturbed regulation of lα,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: phospho-monoesters (PME), P_i, phosphodiesters, and adenosine triphosphate (ATP)-γ -α, and -β. Phosphocreatine was absent. The relative intensity of the renal γATP 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/γATP ratio. The P_i/γATP 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/γATP 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 α-hydroxylase activity and thus have some relevance for pathogenesis of renal hyperparathyroidism.