Chronic kidney disease (CKD) modulates the nonrenal clearance of drugs by altering
their metabolism and/or transport. While the effects of CKD on pathways of oxidative and conjugative
metabolism in the liver are generally understood, the impact of CKD on hepatic reduction
is not. Reduction is a critically important pathway for the metabolism of several drugs and
endogenous compounds. Multiple clinical pharmacokinetic studies have reported changes in the
disposition of hepatic reductase drug substrates in patients with CKD. More recently, data from
experimental studies have shown that kidney disease alters the functional expression of hepatic
reductases. Together, these data suggest that kidney disease may impair the nonrenal clearance
of drugs mediated by reductive pathways. This review synthesizes the current evidence available
regarding the effect of CKD on hepatic reduction. Areas for future investigations are also highlighted.
The growing knowledge of the impact of impaired kidney function on nonrenal drug
clearance may facilitate optimal drug therapy in this patient population.
Keywords: chronic kidney disease, drug disposition, endogenous substrates, metabolism, non-renal clearance, reductase enzymes.
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