Liver Function and Anesthetic Metabolism in Rats with Chronic Renal Impairment

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Abstract
Male Fischer 344 rats with surgically induced CRI [chronic renal impairment] were studied to determine the effect of severe renal impairment: 1st, on in vivo hepatic function as measured by a serum liver enzyme profile, and 2nd, on in vitro hepatic metabolism as indicated by microsomal anesthetic defluorination rates and cytochrome P-450 levels. Rats were operated on in 2 stages, 1 wk apart, and assigned to 1 of 3 groups. Group 1 rats had a capsule stripping of each kidney. Group 2 rats had a capsule stripping of 1 kidney and then a nephrectomy of the other. Group 3 rats had the upper and lower poles of 1 kidney excised and then a nephrectomy of the other. There was no change in renal function in rats from Group 1 and 2. Chronic renal insufficiency in Group 3 rats was manifested by 3-fold elevations in serum creatinine and urea nitrogen levels and reciprocal decreases in clearances. After 89-98 days, blood was obtained for a serum liver enzyme profile and rats were killed for determination of in vitro hepatic metabolism. There were no changes suggestive of hepatic damage. Although there was an approximate 25% decrease in hepatic cytochrome P-450 content in the Group 3 rats, there was no evidence of altered drug metabolism as indicated by the rates of defluorination of methoxyflurane, enflurane, isoflurane or sevoflurane. Lack of unusually high fluoride levels and subsequent nephrotoxicity in subjects with CRI anesthetized with enflurane is apparently not due to decreased hepatic defluorination of the anesthetic.