Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, Indiana.
Kidney360. 2022 Feb;3(2):307-316. doi: 10.34067/kid.0005362021. Epub 2022 Feb 24.
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.
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).
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). -reduced metabolism genotypes were associated with losartan response and uncontrolled hypertension (odds ratio [OR], 5.2; 95% CI, 1.9 to 14.7). -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.
There is a potential role for the addition of pharmacogenomic testing to optimize antihypertensive regimens in patients with CKD.
尽管采用了多种药物治疗，慢性肾脏病（CKD）患者的高血压仍常常得不到控制。药物基因组学药物-基因相互作用（DGIs）可能会影响降压药物的代谢或疗效。我们报告了在提供一组 11 种预测降压反应的药物基因组学预测因子后，高血压控制情况的变化。
前瞻性队列研究纳入 CKD 和高血压患者，以评估药物基因组检测实施的可行性、自我报告的提供者利用情况和血压控制情况。分析人群包括 382 例高血压患者，他们进行了横断面评估 DGIs 的基因分型，335 例患者进行了 1 年随访，以评估收缩压（SBP）和舒张压（DBP）。
大多数（58%）血压控制不佳的高血压患者存在一种或多种降压药物疗效降低的药物基因组学相互作用。与无药物基因组学相互作用的患者相比，有药物基因组学相互作用的患者发生血压控制不佳的可能性高 1.85 倍（95%CI，1.2-2.8 倍），调整种族、医疗体系（安全网医院与其他地点）和晚期 CKD（eGFR <30 ml/min）因素后仍如此。-降低代谢的基因型与氯沙坦的反应和血压控制不佳相关（比值比[OR]，5.2；95%CI，1.9 至 14.7）。与正常代谢者相比，中效或低效代谢者服用美托洛尔或卡维地洛时，血压控制不佳的频率较低（OR，0.55；95%CI，0.3 至 0.95）。在完成 1 年随访的 335 例患者中，SBP（-4.0mmHg；95%CI，1.6 至 6.5mmHg）和 DBP（-3.3mmHg；95%CI，2.0 至 4.6mmHg）均有所改善。有和无药物基因组学相互作用的患者的 SBP 或 DBP 变化无显著差异。
在 CKD 患者中，添加药物基因组学检测以优化降压方案可能具有一定作用。
