Use of drugs with Pharmacogenomics (PGx)-Based Dosing Guidelines in a Danish Cohort of Persons with Chronic Kidney Disease, Both on Dialysis and Not on Dialysis: Perspectives for Prescribing Optimization

BACKGROUND-AIM
Chronic kidney disease (CKD) is a significant public health issue, affecting millions of individuals worldwide. Comorbidities and polypharmacy challenge appropriate treatment of patients with CKD. The Cytochrome P450 (CYP450) drug-metabolizing enzymes play a pivotal role in metabolizing a substantial portion of the prescribed drugs in patients with CKD. Genes responsible for encoding the CYP450 enzyme family exhibit high levels of polymorphism, which result in variations in enzyme activity levels, consequently leading to variations in drug responses and potential side effects. The objective of this registry study is to assess the utilization of PGx drugs among patients with CKD and to explore the potential of integrating PGx-based decision-making into clinical practice.
METHODS
This study was a retrospective study of patients affiliated to the Department of Nephrology, Aalborg University Hospital in The North Denmark Region during 2021. Inclusion criteria was a diagnosis of CKD according to the ICD-10. Patients were divided into 1) CKD without dialysis 2) CKD with dialysis. PGx prescription drugs were retrieved from the Patient Administration System (PAS) including demographic data. Actionable dosing guidelines for specific gene-drug pairs for CYP2D6, CYP2C9, CYP2C19 and SLCO1B1were retrieved from the PharmGKB homepage.
RESULTS
Out of 1241 individuals, 25.5% were on dialysis. The median number of medications for each patient was 9 within the non-dialysis group, and 16 within the dialysis group. In total, 31 distinct PGx drugs were prescribed, representing 13 different subgroups at the ATC level 3. Altogether, 76.0% (943 individuals) were prescribed between 1 and 6 PGx drugs and the prevalence of prescriptions of PGx drugs was higher the dialysis group compared to the non-dialysis group. The most frequently prescribed drugs with actionable dosing guidelines were metoprolol, pantoprazole, atorvastatin, simvastatin, warfarin, clopidogrel, and tramadol. The most frequent dyad was the combination of atorvastatin and metoprolol, and the most frequent triad was the combination of pantoprazole, metoprolol, and atorvastatin, both with prevalence of about 4%.
CONCLUSIONS
This study demonstrated that a substantial proportion of patients with CKD are exposed to drugs or drug combinations for which there exists actionable dosing guidelines related to PGx of CYP2D6, CYP2C19, CYP2C9, and SLCO1B1. These findings underscore the clinical potential of assessing and accounting for genotypic variations and drug-drug interactions.