Pharmacogenomics of Hypertension in CKD: The CKD-PGX Study.

Abstract

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.