Background: 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
Method: 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.
Results: Metabolic enzyme system and transport pathways are dysregulated in both rats and humans with renal
Conclusion: 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.