Raymond A. Lorenz, PharmD, BCPP & Zachary S. Brooks, PhD
Pharmacogenomics in Chronic Kidney Disease. What do the genetics of a patient with chronic kidney disease (CKD) have to do with which medications they may respond to? As it turns out, quite a lot! Patients with CKD will eventually require dialysis or a kidney transplant. In both cases, pharmacogenomics (PGx) offers valuable insights on drug-drug interactions, drug-gene interactions, and precision dosing guidelines (Swen et al., 2023).
76% of CKD patients take at least one medication with PGx dosing guidelines. Polypharmacy is defined as taking five or more medications on a regular basis. It is extremely common in CKD due to comorbidities that almost always accompany it. This puts patients at high risk of both drug-disease and drug-drug interactions (van Oosten et al. 2021). Not only does CKD produce complications of its own (anemia, bone disorders, hyperkalemia), but it typically manifests from pre-existing health issues (diabetes, autoimmune disease, heart failure) as well. A recent retrospective study showed that 76% of all CKD patients were receiving at least one medication with PGx dosing guidelines and that this number was higher in dialysis patients (Westergaard 2024).
Majority of PGx variations occur in cytochrome P-450 enzymes. For anyone dealing with CKD and trying to manage their treatment, PGx can be a game changer. The majority of PGx variations occur in metabolic enzymes of the cytochrome P-450 system, which is located in the liver. These enzymes are especially important in patients with CKD because clinicians may avoid medications cleared by the renal system in order to reduce toxicity risk and monitoring requirements (Kerskes CHM et al. 2023). The reliance on hepatic metabolism means that understanding a patient’s genetic makeup is crucial to tailoring drug therapy according to PGx data.
Precision dosing of immunosuppressants to prevent kidney transplant rejection. For kidney transplant patients, immunosuppressant treatment with drugs like tacrolimus is necessary to prevent organ rejection. Tacrolimus is metabolized in the liver by CYP3A4 and 3A5 enzymes, which cause about 40-50% of all inter-individual variability in the medication’s pharmacokinetics. Thus, precision dosing is paramount to minimizing the likelihood of organ rejection while preventing dug toxicity in this vulnerable patient population. While therapeutic drug monitoring will always be needed, using PGx testing to guide initial dosing of tacrolimus can set clinicians up for success early on in immunosuppressive therapy (Turolo et al. 2023).
Learn more about UGenome’s Personalized Medication Service, ProPEx, or contact UGenome. You can also find case studies for UGenome’s bioinformatics services Metabolite Identification, Bone Metastasis Risk Analysis in Breast Cancer, Survival Analysis with gene signatures in cancer
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