TRANSEPITHELIAL FATE OF BILIRUBIN IN THE ISOLATED RAT-KIDNEY

The renal handling of bilirubin in the rat was studied using an isolat ed kidney preparation by means of the determination of total pigment c oncentration decay in the perfusion medium and its renal clearance. Un conjugated bilirubin was incorporated in the perfusate at a concentrat ion of about 4 mu g/ml. In order to establish the potential role of se cretion in renal handling of the pigment, experiments were also perfor med incorporating in the perfusate different doses of nicotinic acid ( NA) (0.1 and 1.0 mM final concentration), which is considered an alter native substrate for the organic anion transport system, or probenecid (Prob) (0.1 and 1.0 mM final concentration), the classical inhibitor of organic anion transport process. The magnitude of pigment uptake fr om the perfusion medium, estimated by a first order exponential decay constant, was decreased in a dose-dependent way by NA (40 and 76% decr ease for 0.1 and 1.0 mM of NA, respectively) and Prob (57 and 88% decr ease for 0.1 and 1.0 mM of Prob, respectively). NA and Prob also induc ed a diminution in the ratio of pigment renal clearance to glomerular filtration rate (24 and 48% decrease for 0.1 and 1.0 mM of NA and 52 a nd 55% decrease for 0.1 and 1.0 mM of Prob). Based on these findings, it can be proposed that tubular secretion through the proximal cells c ontributes significantly to renal pigment depuration. In order to esta blish the possible contribution of cellular metabolism to the secretor y process, a different set of experiments was conducted. The content o f bilirubin mono and diconjugates (BMC and BDC) were determined in uri ne, in arterial and venous samples and in renal cortex. Studies perfor med using either an open or a closed circulating system, revealed that after conjugation in the renal cell, pigment derivatives can be secre ted into both the tubule and the venous compartments. Total bilirubin concentration as well as the relative content of BMC and BDC in urine increased over time, representing the sum of both conjugates about 50% of the total pigment excreted by the end of experiments. Consequently , our results support the existence of a tubular transepithelial trans port of bilirubin, playing the metabolism of the pigment an important role in this process. (C) 1997 Elsevier Science B.V.