title: Phosphate excretion and phosphate transporter messenger RNA in uremic rats treated with phosphonoformic acid.
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 approximately 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.
authors.affiliation: Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Brooks
authors.forename: S M
authors.initials: SM
authors.lastname: Ali
authors.forename: L C
authors.initials: LC
authors.lastname: Contino
authors.forename: E
authors.initials: E
authors.lastname: Stack
authors.forename: T A
authors.initials: TA
authors.lastname: Fredrickson
authors.forename: J
authors.initials: J
authors.lastname: Feild
authors.forename: R M
authors.initials: RM
authors.lastname: Edwards
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D017245:Foscarnet / Q000494:pharmacology*; D007674:Kidney Diseases / Q000378:metabolism*; D008297:Male; D009392:Nephrectomy; D028044:Phosphate-Binding Proteins; D010710:Phosphates / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002352:Carrier Proteins; D028044:Phosphate-Binding Proteins; D010710:Phosphates; D012333:RNA, Messenger; D017245:Foscarnet