DRUG GLUCURONIDATION BY HUMAN RENAL UDP-GLUCURONOSYLTRANSFERASES

The UDP-glucuronosyltransferases catalyse the conjugation of glucuroni c acid to a wide variety of endobiotics and xenobiotics, representing one of the major conjugation reactions in the conversion of both exoge nous (e.g. drugs and pesticides) and endogenous compounds (e.g. biliru bin and steroid hormones). The liver is the major site of glucuronidat ion, however a number of extrahepatic tissues exhibit particular UDP-g lucuronosyltransferase activities. The present study was undertaken to assess the human renal UDP-glucuronosyltransferase system. Enzymatic analysis of human kidney showed that a limited number of UDP-glucurono syltransferase isoforms were expressed in this tissue. However the lev el of renal UGT activity towards the anaesthetic propofol was higher c ompared with human liver. The glucuronidation of propofol is catalysed by UGT1A8/9 suggesting higher levels of this isoform in the kidney. I mmunoblot analysis revealed two major UDP-glucuronosyltransferase immu nopositive bands to be present in human kidney as compared to four maj or bands in human liver. The human kidney was capable of conjugating v arious structurally diverse drugs and xenobiotics. (C) 1998 Elsevier S cience Inc.