Disposition of L-carnitine and acetyl-L-carnitine in the isolated perfused rat kidney

The isolated perfused rat kidney was used to investigate the regulation, specificity and concentration-dependence of the renal tubular disposition of L-carnitine (LC) and its ester, acetyl-L-carnitine (ALC). Tritiated markers were used to study the renal disposition of LC and ALC and HPLC was used to purify 3H-LC and 3H-ALC before radiochemical analysis. At perfusate concentrations comparable to those found in plasma in vivo (50 microM for LC and 5 microM for ALC), the renal clearance of both analogues was substantially less than GFR (P < .05) which, in view of their negligible binding to perfusate proteins, is indicative of extensive reabsorption. During the first 20 min of perfusion, the percent tubular reabsorption (%TR) of LC and ALC was 94 +/- (SD) 2.6% and 97 +/- 0.6%, respectively. The extent of 3H-ALC and 3H-LC enrichment of perfusate in experiments with 3H-LC and 3H-ALC, respectively, provided evidence for the capability of the rat kidney to acetylate LC and deacetylate ALC. In addition, a portion of renally generated 3H-ALC and 3H-LC was found to undergo leakage into renal tubules and escape subsequent reabsorption. It was also found that the %TR of both compounds decreased substantially when the perfusate concentration was increased above endogenous levels; each compound was capable of decreasing the %TR of the other; and trimethylamine-N-oxide, a metabolite of LC, had no significant effect on the renal handling of the carnitine derivatives.