Abstract
The prevention of phosphate retention in chronic renal disease may reduce both renal osteodystrophy and disease progression. We evaluated the expression of the sodium-dependent phosphate transporter, NaPi-2, and the response to phosphonoformic acid (PFA) in rats with 5/6 nephrectomy-induced renal failure. Partial nephrectomy resulted in a significant proteinuria and reduced renal function. In addition, there was an ∼50% reduction in the expression of NaPi-2 mRNA. Treatment of rats for 48 hr with PFA (0.6% in glucose drinking fluid) had no effect on NaPi-2 mRNA; however, PFA resulted in a significant increase in fractional phosphate excretion in both normal (7 ± 0.5%vs. 3 ± 0.2%) and uremic (60 ± 4%vs. 36 ± 4%) rats. Plasma phosphate concentration was higher in uremic rats (2.5 ± 0.1 mM) compared with normal rats (1.9 ± 0.04 mM) but not in uremic rats treated with PFA (2.1 ± 0.04 mM). These data suggest that PFA can increase renal phosphate excretion independent of changes in phosphate transporter expression and prevent phosphate retention.
Footnotes
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Send reprint requests to: David Brooks, Ph.D., SmithKline Beecham, Department of Renal Pharmacology, UW2521, P.O. Box 1539, King of Prussia, PA 19406-0939.
- Abbreviations:
- PFA
- phosphonoformic acid
- NaPi
- sodium phosphate
- SGT
- sodium glucose cotransporter
- PCR
- polymerase chain reaction
- SDS
- sodium dodecyl sulfate
- GAPDH
- glyceraldehyde-3-phosphate dehydrogenase
- Received August 26, 1996.
- Accepted February 3, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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