Metabolic Enzyme System and Transport Pathways in Chronic Kidney Diseases.

Abstract

Chronic Kidney Disease (CKD), a global public health problem, affects numerous people worldwide, and the prevalence is rising. Results from animal experiments and clinical investigations have demonstrated that drug metabolic enzymes and transporters-mediated non-renal clearance are dramatically impaired in CKD, co-respondent with alterations in the elimination of metabolized drugs. Accumulated uremic toxins may downregulate or directly inhibit the activity and/or the expression of drug metabolic enzymes and transporters, which may result in unintended alterations of drug exposure and response in cases when drugs dose are not adjusted for the renal dysfunction. The aim of this review is to highlight the impact of CKD on non-renal drug clearance involving metabolism enzyme system and transport pathways, and to provide insight into the impact of non-renal drug clearance on drug metabolism and distribution in CKD patients. Metabolic enzyme system and transport pathways are dysregulated in both rats and humans with renal failure. The alterations of drug metabolic enzymes and transporters in the kidney, liver, and intestine play an important role in their pharmacokinetic changes, and thus, the metabolism and transportation of many medications used to treat CKD patients may be affected.