Vol. 281, Issue 3, 1440-1445, 1997

Phosphate Excretion and Phosphate Transporter Messenger RNA in Uremic Rats Treated with Phosphonoformic Acid

David P. Brooks, Shujath M. Ali, Lisa C. Contino, Elwood Stack, Todd A. Fredrickson, John Feild and Richard M. Edwards

Departments of Renal Pharmacology (D.P.B., S.M.A., L.C.C., E.S., T.A.F., R.M.E.) and Molecular Genetics (J.F.), SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania

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.