Effects of Chronic Renal Failure and Hemodialysis on the Monoethylglycinexylidide Liver Function Test

Abstract

Monoethylglycinexylidide (MEGX), the primary metabolite of lidocaine, is produced via oxidative N-deethylation catalyzed by cytochrome P450 (CYP) 3A4 (1). The MEGX test, a new dynamic test of liver function that assesses the rate of MEGX formation after a standard intravenous dose of lidocaine, is a highly sensitive indicator of hepatic dysfunction and has gained the widest acceptance among dynamic liver function tests, especially in the field of liver transplantation (2). Although various observations have provided evidence of impaired drug metabolism in patients with renal insufficiency (3), the effect of renal function on MEGX formation rate has received limited attention. The only study comparing uremic patients with healthy subjects found no statistically significant differences in MEGX values between the two study groups (4). However, in this investigation, only patients with moderate kidney dysfunction were examined and MEGX was measured only 15 min after lidocaine injection. Although this was the sampling time originally suggested by Oellerich et al. (5), these authors later observed a lesser variability in MEGX concentrations at 30 min and proposed that blood be sampled at this time for MEGX determination (6). We have shown that the intersubject variability in MEGX decreases up to 1 h in both healthy individuals and cirrhotic patients; consequently, the efficiency of the test becomes maximal when blood is sampled 60 min after lidocaine injection (7). This result was confirmed in subsequent studies (8)(9)(10). The aim of the present study was to reassess the effect of chronic renal failure on the results of the MEGX test. We studied 48 Caucasian men with informed written consent. The study protocol was approved by the local Ethics Committee. The subjects were divided into four groups on the basis of creatinine clearance (CLCR) values: Group 1, with CLCR >80 mL/min per 1.73 …