Pharmacogenomics of Hypertension in CKD: The CKD-PGX Study
Michael T. Eadon, Judith Maddatu, Sharon M. Moe, Arjun Sinha, Ricardo Melo Ferreira, Brent W. Miller, S. Jawad Sher, Jing Su, Victoria M. Pratt, Arlene B. Chapman, Todd C. Skaar, Ranjani N. Moorthi
Abstract
Key Points The CKD-PGX study assessed the feasibility of pharmacogenomic testing for a panel of antihypertensive agent efficacy predictors. Most patients with uncontrolled hypertension had one or more drug-gene interactions predicting reduced efficacy of their medications. In 36% of cases, practitioners used genetic data to change BP management in their patients with CKD. Background Patients with CKD often have uncontrolled hypertension despite polypharmacy. Pharmacogenomic drug-gene interactions (DGIs) may affect the metabolism or efficacy of antihypertensive agents. We report changes in hypertension control after providing a panel of 11 pharmacogenomic predictors of antihypertensive response. Methods A prospective cohort with CKD and hypertension was followed to assess feasibility of pharmacogenomic testing implementation, self-reported provider utilization, and BP control. The analysis population included 382 subjects with hypertension who were genotyped for cross-sectional assessment of DGIs, and 335 subjects followed for 1 year to assess systolic BP (SBP) and diastolic BP (DBP). Results Most participants (58%) with uncontrolled hypertension had a DGI reducing the efficacy of one or more antihypertensive agents. Subjects with a DGI had 1.85-fold (95% CI, 1.2- to 2.8-fold) higher odds of uncontrolled hypertension, as compared with those without a DGI, adjusted for race, health system (safety-net hospital versus other locations), and advanced CKD (eGFR <30 ml/min). CYP2C9 -reduced metabolism genotypes were associated with losartan response and uncontrolled hypertension (odds ratio [OR], 5.2; 95% CI, 1.9 to 14.7). CYP2D6 -intermediate or -poor metabolizers had less frequent uncontrolled hypertension compared with normal metabolizers taking metoprolol or carvedilol (OR, 0.55; 95% CI, 0.3 to 0.95). In 335 subjects completing 1-year follow-up, SBP (−4.0 mm Hg; 95% CI, 1.6 to 6.5 mm Hg) and DBP (−3.3 mm Hg; 95% CI, 2.0 to 4.6 mm Hg) were improved. No significant difference in SBP or DBP change were found between individuals with and without a DGI. Conclusions There is a potential role for the addition of pharmacogenomic testing to optimize antihypertensive regimens in patients with CKD.