Renal UDP-glucuronosyltransferases and the glucuronidation of xenobiotics and endogenous mediators

Abstract

The role of the kidney in drug and chemical disposition has traditionally focused on the excretion of polar xenobiotics and metabolites. However, there is increasing evidence demonstrating that renal UGTs are integral to the “local” intrarenal, and, possibly, systemic, metabolic clearance of numerous drugs and nondrug xenobiotics, as well as to the maintenance of renal homeostasis through limiting the biological activity of endogenous renal mediators that control electrolyte balance and renal blood flow. The common involvement of UGT1A9 and UGT2B7 in the metabolism of both endogenous and exogenous compounds in kidney predicates significant renal drug-endobiotic interactions that may explain, in part, the adverse renal effects of some drugs.

Keywords::

• Human kidney
• renal drug metabolism
• UDP-glucuronosyltransferase
• glucuronidation

Acknowledgments

The authors acknowledge funding by Flinders University and the National Health and Medical Research Council of Australia.