Disposition of creatinine and urea in bilaterally nephrectomized rats

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 hours following intravenous administration of [carbonyl-14C] creatinine immediately and 24 hours after nephrectomy was 0.54 and 3.24% respectively, and these values were significantly different (p less than 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 that intestinal contents, but 14CO2 was not produced. When the mixture of the metabolites was administered orally or intravenously to chronically creatinine loaded rats, however, about 50% of the total radioactivity was excreted into the expired air in 5 hours. Furthermore, biliary excretion of the radioactivity following intravenous administration of [carbonyl-14] creatinine in the nephrectomized rats was much greater than that in normal rats. These results indicate that expiratory excretion following intravenous administration [carbonyl-14C] creatinine 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 bilaterally nephrectomy was also studied to compare with that for creatinine.