Prevention of phosphate-induced progression of uremia in rats by 3-phosphocitric acid.
Male Sprague-Dawley rats were rendered uremic by surgical removal of 70% of functioning renal mass. This produced a rapid threefold rise in serum creatinine to 0.87 +/- 0.067 (SEM) mg/dl at 2 weeks postoperatively which declined subsequently to a value of 0.64 +/- 0.06 (SEM) and remained stable thereafter for an additional 4 weeks in animals maintained on a diet with normal phosphate content. Increase of dietary phosphate content to 2.2% at 2 weeks after surgery produced a significant and progressive increase in serum creatinine to values fourfold higher than the mean values in comparable partially nephrectomized control animals maintained on a diet with normal phosphate content (P less than 0.001). This deterioration in renal function was associated with extensive nephrocalcinosis, tubular dilatation, cellular necrosis, and marked interstitial inflammation. 3-phosphocitric acid, a compound which has been shown to prevent calcium phosphate crystal growth as well as to prevent in vivo nephrocalcinosis, was very effective in preventing this phosphate-induced deterioration of renal function and in preventing any significant increase in renal calcium content in animals fed a high phosphate diet. This compound was also effective in preventing the renal histologic changes associated with phosphate-induced uremia.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002951:Citrates / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D004032:Diet; D007668:Kidney / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D009392:Nephrectomy; D010710:Phosphates / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014511:Uremia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
D002951:Citrates; D010710:Phosphates; C014148:phosphocitrate; D003404:Creatinine; D002118:Calcium