Use of phosphonoformic acid to induce phosphaturia in chronic renal failure in rats.
In chronic renal failure (CRF), phosphate (Pi) retention may lead to secondary hyperparathyroidism and progression to end-stage renal disease (ESRD). Dietary phosphorus restriction or phosphate binders can slow progression in experimental CRF. Conversely, diets high in phosphorus can accelerate the progression toward ESRD. Phosphate binders reduce intestinal Pi absorption but have no effect on its renal excretion. Phosphonoformic acid (PFA, foscarnet) is a specific inhibitor of both intestinal and renal brush border Na(+)-Pi cotransport. It causes phosphaturia when administered parenterally or orally to rats. To determine the effect of oral PFA on renal function and on phosphate excretion in renal insufficiency, PFA was administered in drinking water to rats with CRF produced by 5/6th nephrectomy. Blood and 24-h urine collections were performed every 2 weeks for determination of plasma Pi and creatinine concentrations, urinary protein excretion, and urinary creatinine and Pi clearances. PFA, administered for 8 weeks, did not exert any adverse effects on any of the measured parameters. The slopes of the reciprocal of plasma creatinine versus time were not different between control and PFA-treated rats. Although PFA increased Pi excretion over the baseline, it had no persistent effect on plasma Pi concentrations under these experimental conditions.
Loghman-Adham
M
M
Department of Pediatrics, University of Utah School of Medicine, Salt Lake City 84132, USA.
Motock
G T
GT
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D017245:Foscarnet / Q000008:administration & dosage / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000473:pathology; D007677:Kidney Function Tests; D010710:Phosphates / Q000097:blood / Q000378:metabolism* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D016482:Urinalysis
D010710:Phosphates; D018894:Reverse Transcriptase Inhibitors; D017245:Foscarnet