Implications of Kidney Disease on Metabolic Reduction

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.