Disposition of creatinine and urea in bilaterally nephrectomized rats.

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Abstract
Bilaterally nephrectomized rats were used to investigate the disposition of creatinine when renal function is acutely decreased. The percentage of radioactivity recovered in the expired air in 11 h following i.v. administration of [carbonyl-14C]creatinine immediately and 24 h after nephrectomy was 0.54 and 3.24%, respectively, and these values were significantly different (P < 0.05). As it was considered that expiratory excretion is one of the major elimination routes in nephrectomized rats, mechanism of expiratory excretion was investigated by incubating [carbonyl-14C]creatinine with the intestinal contents of the rats chronically loaded with creatinine. [carbonyl-14C]Creatinine was completely metabolized in the intestinal contents but 14CO2 was not produced. When the mixture of the metabolites was administered orally or i.v. to chronically creatinine loaded rats, about 50% of the total radioactivity was excreted into the expired air in 5 h. Biliary excretion of the radioactivity following i.v. administration of [carbonyl-14C]creatinine in the nephrectomized rats was much greater than that in normal rats. Expiratory excretion following i.v. [carbonyl-14C]creatinine administration to nephrectomized rats would arise following intestinal absorption of the creatinine metabolites, which seem to be produced by intestinal microflora after biliary excretion of creatinine. The change of disposition for urea by bilateral nephrectomy was also compared with that for creatinine.