Abstract: TH-PO0825
Integrating Pharmacogenomics into Nephrology: Optimizing Drug Therapy and Reducing Adverse Drug Reactions in Kidney Disease and Transplant Care
Session Information
- Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 1900 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Nobakht, Ehsan, Precision Medicine Care, Germantown, Maryland, United States
- Dadgar, Sherry, Precision Medicine Care, Germantown, Maryland, United States
Background
Chronic Kidney Disease (CKD) affects 10–15% of the global population and increases adverse drug reaction (ADR) risk due to impaired renal clearance, altered pharmacokinetics, and polypharmacy; 27–32% of serious ADRs in CKD are potentially preventable. Uremia downregulates hepatic and intestinal drug-metabolizing enzymes via uremic toxins and proinflammatory cytokines. Germline pharmacogenomic (PGx) variants add further variability. Kidney transplant recipients are especially vulnerable, requiring lifelong narrow therapeutic index immunosuppressants, commonly used antiplatelet agents, and analgesics with established PGx associations. The RenaPGx® panel provides actionable PGx guidance for these patients.
Methods
PMC® performed PGx testing on 112 ethnically diverse individuals (Caucasian, African American, Asian). Three drug-gene pairs common in transplant care were examined: tacrolimus/CYP3A5, clopidogrel/CYP2C19, and codeine/CYP2D6. CPIC guidelines, PharmGKB, and FDA labels informed the analysis.
Limitations:
Subjects did not have kidney disease. However, PGx variants are germline and stable; allele frequencies in diverse healthy cohorts are extrapolable to kidney disease populations of similar ancestry.
Results
CYP2C19: 45.9% were poor (10.1%) or intermediate (35.8%) metabolizers; CPIC recommends alternative antiplatelet therapy as loss-of-function alleles impair clopidogrel bioactivation. CYP2D6: 55.4% were intermediate metabolizers with reduced morphine formation, 2.7% poor, and 2.7% ultrarapid metabolizers; CPIC and FDA recommend avoiding codeine in ultrarapid (toxicity from excessive morphine formation) and poor (lack of efficacy) metabolizers. CYP3A5: 21.8% were expressors requiring higher tacrolimus starting doses (1.5–2× standard, ≤0.3 mg/kg/day) per CPIC. A substantial proportion carried non-normal phenotypes across multiple drug-gene pairs.
Conclusion
A substantial proportion of individuals carry actionable PGx variants affecting medications commonly used in transplant popuation. RenaPGx® testing guides drug selection and dosing where complex regimens and narrow therapeutic indices increase ADR risk. Integrating PGx into nephrology may improve efficacy, reduce toxicity, and advance precision medicine.