Marlon T. Makwara & Jayden Lee, PharmD
- APOL1 risk variants predict rapid CKD progression and drug response in patients of African ancestry
- CYP3A5 genotyping guides optimal immunosuppressant dosing in kidney transplant recipients
- Genetic biomarkers are potential sources of diagnostic, prognostic, and therapeutic information that can impact the clinical management of people with CKD
Chronic kidney disease (CKD) affects an estimated 850 million people globally as of 2021 (Halder et al., 2024). Conventional treatment of CKD is typically limited to managing comorbidities (hypertension, diabetes, etc.) and complications (anemia, hyperkalemia, transplant, etc). Pharmacogenomics (PGx) now enables precision kidney care through comprehensive gene panels, variant risk stratifications, and genotype-guided dosing.
Kidney impairment raises drug exposure, significantly increasing the risk of toxicity. Even when accounted for, dose adjustments often ignore underlying genetic pharmacokinetic differences. A 2022 Mayo Clinic study analyzed 15 genes in 1,200 CKD patients. Those receiving genotype-guided prescriptions experienced 52% fewer adverse drug events and 35% lower hospitalization rates compared to those receiving standard care (Sanchez-Rodriguez et al., 2021). The widespread adoption of comprehensive PGx panels promises substantial benefits for both patients and the healthcare system.
APOL1 variants are the strongest predictors of CKD development and progression, especially among patients of African ancestry (KDIGO, 2024). High-risk genotypes are associated with up to 40% faster decline in glomerular filtration rate and altered responses to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aliskiren. 13 additional genetic biomarkers have been identified in the 2024 KDIGO guidelines that may establish the cause of CKD and potential drug targets.
For kidney transplant recipients, CYP3A5 genotyping can reduce the risk of rejections. Rapid and ultrarapid metabolizers require 2-4× higher initial doses of tacrolimus to achieve therapeutic ranges. In a 2023 Johns Hopkins cohort, implementing preemptive testing reduced acute kidney rejection by 31% and drug-induced nephrotoxicity by 44% (Birdwell et al., 2015). For patients and healthcare professionals, this genetic revolution promises longer-lasting grafts and fewer complications, one transplant at a time.
1. Birdwell KA, Decker B, Barbarino JM, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP3A5 genotype and tacrolimus dosing. Clin Pharmacol Ther. 2015;98(1):19-24. doi:10.1002/cpt.113
2. Halder, R.K., Uddin, M.N., Uddin, M.A., Aryal, S., Saha, S., Hossen, R., Ahmed, S., Rony, M.A.T. and Akter, M.F. (2024) ‘ML-CKDP: Machine learning-based chronic kidney disease prediction with smart web application’, Journal of Pathology Informatics, 15, p. 100371
3. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2024) ‘KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease’, Kidney International, 105(4S), pp. S117–S314.4. Sanchez-Rodriguez E, Kalim S, Wilcox J, et al. Pharmacogenomics in kidney disease: report of a symposium. Clin J Am Soc Nephrol. 2021;16(1):140-146. doi:10.2215/CJN.15040820