Lee Fei Yee, Islahudin Farida, Abdul Gafor Abdul Halim, Wong Hin-Seng, Bavanandan Sunita, Mohd Saffian Shamin, Md Redzuan Adyani, Makmor-Bakry Mohd
Centre for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Clinical Research Centre, Hospital Selayang, Ministry of Health Malaysia, Batu Caves, Malaysia.
Front Pharmacol. 2022 Mar 14;13:848804. doi: 10.3389/fphar.2022.848804. eCollection 2022.
Chronic kidney disease (CKD) patients may be more susceptible to adverse drug reactions (ADRs), given their complex medication regimen and altered physiological state driven by a decline in kidney function. This study aimed to describe the relationship between polymorphism and the ADR of antihypertensive drugs in CKD patients. This retrospective, multi-center, observational cohort study was performed among adult CKD patients with a follow-up period of up to 3 years. ADRs were detected through medical records. genotyping was performed using the direct sequencing method. From the 200 patients recruited in this study, 33 (16.5%) were found to have ADRs related to antihypertensive drugs, with 40 ADRs reported. The most frequent ADR recorded was hyperkalemia (n = 8, 20.0%), followed by bradycardia, hypotension, and dizziness, with 6 cases (15.0%) each. The most common suspected agents were angiotensin II receptor blockers (n = 11, 27.5%), followed by angiotensin-converting enzyme inhibitors (n = 9, 22.5%). The polymorphism was not found to be associated with antihypertensive-related ADR across the genetic models tested, despite adjustment for other possible factors through multiple logistic regression ( > 0.05). After adjusting for possible confounding factors, the factors associated with antihypertensive-related ADR were anemia (adjusted odds ratio [aOR] 5.438, 95% confidence interval [CI]: 2.002, 14.288) and poor medication adherence (aOR 3.512, 95% CI: 1.470, 8.388). In conclusion, the polymorphism was not found to be associated with ADRs related to antihypertensives in CKD patients, which requires further verification by larger studies.
慢性肾脏病（CKD）患者由于其复杂的用药方案以及肾功能下降导致的生理状态改变，可能更容易发生药物不良反应（ADR）。本研究旨在描述CKD患者中基因多态性与抗高血压药物ADR之间的关系。本研究为回顾性、多中心、观察性队列研究，在成年CKD患者中进行，随访期长达3年。通过病历检测ADR。使用直接测序法进行基因分型。在本研究招募的200例患者中，发现33例（16.5%）发生了与抗高血压药物相关的ADR，共报告了40例ADR。记录到的最常见ADR是高钾血症（n = 8，20.0%），其次是心动过缓、低血压和头晕，各有6例（15.0%）。最常见的可疑药物是血管紧张素II受体阻滞剂（n = 11，27.5%），其次是血管紧张素转换酶抑制剂（n = 9，22.5%）。尽管通过多因素logistic回归对其他可能因素进行了校正（P>0.05），但在所测试的遗传模型中，未发现该基因多态性与抗高血压相关ADR有关。在调整了可能的混杂因素后，与抗高血压相关ADR相关的因素是贫血（校正比值比[aOR] 5.438，95%置信区间[CI]：2.002，14.288）和用药依从性差（aOR 3.512，95%CI：1.470，8.388）。总之，未发现该基因多态性与CKD患者抗高血压药物相关的ADR有关，这需要更大规模的研究进一步验证。
