Abstract
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 CYP3A5*3 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. CYP3A5*3 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 CYP3A5*3 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 (p > 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 CYP3A5*3 polymorphism was not found to be associated with ADRs related to antihypertensives in CKD patients, which requires further verification by larger studies.
Highlights
An adverse drug reaction (ADR) is defined as a noxious and unintended reaction to a drug at doses normally used in humans (World Health Organization, 2002)
This study provides a novel, pharmacogenomics-driven approach to assess ADRs related to antihypertensives in Chronic kidney disease (CKD)
CKD patients might be more susceptible to ADRs given the need for multiple medications, in addition to physiological differences contributed by kidney function decline
Summary
An adverse drug reaction (ADR) is defined as a noxious and unintended reaction to a drug at doses normally used in humans (World Health Organization, 2002). Among patients with chronic illness, chronic kidney disease (CKD) patients frequently report ADR. ADRs could be potentially difficult to be predicted, given the multifactorial nature of ADRs, especially among CKD patients. Due to different physiological factors as a result of kidney function decline, it is difficult to extrapolate findings on the propensity of ADRs from existing studies among the general population to CKD patients. The unpredictable interindividual drug responses in the form of ADR might be driven by genetic polymorphisms that affect drug metabolism pathways and drug metabolism activity (Zanger and Schwab, 2013). Genetic polymorphisms that affect the drug metabolism pathways, such as the cytochrome P (CYP) 450 system, are of clinical prominence, as CYP450 metabolizes more than 80% of drugs (Zanger and Schwab, 2013). CYP450 pharmacogenomics might be a promising approach to mitigate ADRs, especially in CKD patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
