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.

AIM: The objective of this registry study is to assess the utilization of pharmacogenomic (PGx) drugs among patients with chronic kidney disease (CKD). METHODS: This study was a retrospective study of patients affiliated with the Department of Nephrology, Aalborg University Hospital, Denmark in 2021. Patients diagnosed with CKD were divided into CKD without dialysis and CKD with dialysis. PGx prescription drugs were retrieved from the Patient Administration System. Actionable dosing guidelines (AG) for specific drug-gene pairs for CYP2D6, CYP2C9, CYP2C19 and SLCO1B1 were 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. Thirty-one distinct PGx drugs were prescribed. Altogether, 76.0% (943 individuals) were prescribed at least one PGx drug and the prevalence of prescriptions of PGx drugs was higher in the dialysis group compared to the non-dialysis group. The most frequently prescribed drugs with AG were metoprolol, pantoprazole, atorvastatin, simvastatin and warfarin. CONCLUSION: This study demonstrated that a substantial proportion of patients with CKD are exposed to drugs or drug combinations for which there exists AG related to PGx of CYP2D6, CYP2C19, CYP2C9 and SLCO1B1.

Incidence of hospital contacts with acute kidney injury after initiation of second-generation antipsychotics in older adults: a Danish population-based cohort study.

PURPOSE: To investigate the association between acute kidney injury (AKI) and use of second-generation antipsychotics (SGA) in older adults. METHODS: In a population-based cohort study using Danish national registries, new users of SGAs (aged ≥ 65) were identified during 2005-2015. Each SGA user was matched to 10 population controls on age, sex, and the SGA initiation date. The outcome was incident AKI within 90 days after the index date. Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for potential confounders. RESULTS: In the study, 36,581 new SGA users and 365,810 controls were included. The 90-day incidence rate of AKI was 4.38 and 1.70 per 1000 person-years among SGA users and controls, respectively, corresponding to a crude HR of 2.57 (1.79-3.68). The fully adjusted HR (aHR) was 1.43 (0.89-2.27) for all SGAs. The risk differed among individual drugs with aHRs for olanzapine 3.50 (1.20-10.23), quetiapine 1.62 (0.81-3.26), and risperidone 0.68 (0.28-1.64). In sensitivity analyses, the aHR declined to 1.24 (0.95-1.61) at 1-year follow-up. CONCLUSIONS: Olanzapine use was associated with a significantly increased 90-day AKI risk. For quetiapine, the risk was elevated but not significant, and risperidone had no association. CIs were wide and confounder adjustment largely impacted the estimates. Main limitations included residual confounding and incomplete recording of AKI diagnoses.