Drug Metabolism Considerations in Patients With Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD) is a progressive process leading to end stage renal disease and either dialysis or transplantation. Patients with CKD often have numerous comorbid conditions such as diabetes, hypertension, and acid-base and electrolyte disorders that can lead to alterations in homeostasis. Changes in drug disposition including hepatic metabolism via phase 1 (ie, cytochrome P-450 enzymes) and phase 2 (ie, conjugation) pathways have been reported. Biotransformation of drugs and endogenous substances within the kidney itself may also be compromised in the presence of CKD. Reduced hepatic and renal clearance leads to systemic accumulation of the parent drug as well as active and toxic metabolites. Characterization of specific hepatic cytochrome (CYP) enzyme pathways in patients with CKD is an area of current research and will lead to an understanding of phenotypic and genotypic expression patterns of several key drug-metabolizing enzymes. The evolving knowledge of CYP enzymes and the alterations that can occur in CKD should allow clinicians to predict adverse consequences of drug therapy and thus prevent these events from occurring. The pharmacy practitioner can also provide important pharmacotherapy interventions in this special patient population, including dose individualization, therapeutic drug monitoring, and evaluation of therapeutic outcomes.