Sarhan Neven, Schaalan Mona F, El-Sheikh Azza A K, Zarif Bassem
Clinical Pharmacy Department, Faculty of Pharmacy, Misr International University, Cairo 11314, Egypt.
Basic Health Sciences Department, College of Medicine, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
Pharmaceutics. 2025 Jul 24;17(8):959. doi: 10.3390/pharmaceutics17080959.
: Heart failure with reduced ejection fraction (HFrEF) is associated with significant renal complications, affecting disease progression and patient outcomes. Sodium-glucose co-transporter-2 (SGLT2) inhibitors have emerged as a key therapeutic strategy, offering cardiovascular and renal benefits in these patients. However, interindividual variability in response to dapagliflozin underscores the role of pharmacogenetics in optimizing treatment efficacy. This study investigates the influence of genetic polymorphisms on renal outcomes in HFrEF patients treated with dapagliflozin, focusing on variations in genes such as , , , and . : This prospective, observational cohort study was conducted at the National Heart Institute, Cairo, Egypt, enrolling 200 patients with HFrEF. Genotyping of selected single nucleotide polymorphisms (SNPs) was performed using TaqMan™ assays. Renal function, including estimated glomerular filtration rate (eGFR), Kidney Injury Molecule-1 (KIM-1), and Neutrophil Gelatinase-Associated Lipocalin (NGAL) levels, was assessed at baseline and after six months of dapagliflozin therapy. : Significant associations were found between genetic variants and renal outcomes. Patients with AA genotype of rs3813008 () exhibited the greatest improvement in eGFR (+7.2 mL ± 6.5, = 0.004) and reductions in KIM-1 (-0.13 pg/mL ± 0.49, < 0.0001) and NGAL (-6.1 pg/mL ± 15.4, < 0.0001). Similarly, rs12917707 () TT genotypes showed improved renal function. However, rs5219 () showed no significant impact on renal outcomes. : Pharmacogenetic variations influenced renal response to dapagliflozin in HFrEF patients, particularly in and genes. These findings highlighted the potential of personalized medicine in optimizing therapy for HFrEF patients with renal complications.
射血分数降低的心力衰竭（HFrEF）与严重的肾脏并发症相关，影响疾病进展和患者预后。钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂已成为一种关键的治疗策略，为这些患者带来心血管和肾脏益处。然而，达格列净治疗反应的个体差异凸显了药物遗传学在优化治疗效果中的作用。本研究调查基因多态性对接受达格列净治疗的HFrEF患者肾脏预后的影响，重点关注 、 、 和 等基因的变异。：这项前瞻性观察性队列研究在埃及开罗国家心脏研究所进行，纳入200例HFrEF患者。使用TaqMan™ 分析法对选定的单核苷酸多态性（SNP）进行基因分型。在基线和达格列净治疗6个月后评估肾功能，包括估计肾小球滤过率（eGFR）、肾损伤分子1（KIM-1）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）水平。：发现基因变异与肾脏预后之间存在显著关联。rs3813008（）AA基因型患者的eGFR改善最大（+7.2 mL ± 6.5， = 0.004），KIM-1降低（-0.13 pg/mL ± 0.49， < 0.0001），NGAL降低（-6.1 pg/mL ± 15.4， < 0.0001）。同样，rs12917707（）TT基因型显示肾功能改善。然而，rs5219（）对肾脏预后无显著影响。：药物遗传学变异影响HFrEF患者对达格列净的肾脏反应，特别是在 和 基因中。这些发现凸显了个性化医疗在优化有肾脏并发症的HFrEF患者治疗方面的潜力。
