Evidence for bidirectional net movement of creatinine in the rat kidney

Although the clearance of endogenous creatinine is used in many physiologic and metabolic studies in the rat as an index of glomerular filtration rate, there is no evidence that creatinine is a reliable test substance. Studies were therefore performed in anesthetized and conscious rats to determine the creatinine-to-inulin clearance ratio (CCr/CIn). In anesthetized animals the CCr/CIn ratio was 0.5 and in conscious rats it was 0.7 at normal basal plasma creatinine levels. After an increase in plasma creatinine to 1.9 mg/dl induced by the intravenous infusion of creatinine, the CCr/CIn ratio was 1.2. Accordingly, these data indicate that net creatinine transport across the renal tubule is bidirectional and that transport is influenced by the plasma creatinine level. At normal plasma levels creatinine is extensively reabsorbed along the nephron, whereas net secretion is associated with elevated plasma creatinine. The results demonstrate that creatinine is not a reliable marker of glomerular filtration rate in the rat.