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 threshold 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 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 < 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.