Creatinine Metabolism in Humans with Decreased Renal Function: Creatinine Deficit

Abstract

This study was designed to test the hypothesis that, in a patient with decreased renal function and an increased plasma creatinine concentration, a significant quantity of creatinine is excreted into the gut, as is true of urea and uric acid, and is metabolized by gut flora. [Methyl-¹⁴C] creatinine was given intravenously to five patients and [methyl-¹⁴C] creatinine or [carbonyl-¹⁴C] creatinine was given orally to five patients. Extracts of excreta, plasma, and urine were subjected to ion-exchange chromatography, with monitoring for ¹⁴C and for ninhydrin-positive material. Respiratory gases, collected in acid and base, were assayed for radioactivity. Blood specimens were obtained at intervals to furnish data on decay of labeled creatinine in the body pool. The data show that there is a true creatinine deficit (15.9 to 65.7% of the creatinine formed is metabolized or excreted via extrarenal routes) in patients with decreased renal function. In these patients, creatinine is metabolized to CO₂ and methylamine, presumably by the microflora of the gut. A significant portion of the carbonyllabeled creatinine appeared in plasma in an unidentified compound.