<![CDATA[This study aims to synthesize scientific evidence on pharmacogenomic interactions in antihypertensive polypharmacy and their association with intradialytic complications among chronic kidney disease (CKD) patients undergoing hemodialysis using a Systematic Literature Review (SLR) approach. A systematic literature search was conducted across PubMed, Scopus, Google Scholar, and Wiley Online Library for publications from 2017 to 2025, following the PRISMA guidelines and the PICO framework. A total of 30 articles met the inclusion criteria and were synthesized narratively. The findings indicate that antihypertensive polypharmacy is highly prevalent in the hemodialysis population, with an average use of ≥5–10 medications. The most frequently reported pharmacogenomic interactions involved phase I metabolic genes, particularly CYP2D6 and CYP2C9, influencing responses to beta-blockers and angiotensin receptor blockers (ARBs). Drug–drug–gene interactions in intensive polypharmacy conditions were associated with increased risks of intradialytic hypotension, intradialytic hypertension, bradycardia, electrolyte disturbances, and reduced quality of life. This synthesis highlights that intradialytic complications are influenced not only by drug class or dosing time but also by a combination of genetic factors, renal function, and medication burden. The integration of pharmacogenomic approaches, comprehensive polypharmacy evaluation, and clinical pharmacist involvement holds potential to improve patient safety and hemodynamic stability in hemodialysis patients.]]>
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