Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Monazamet El-Wehda El-Afriqeya St., Abbassia, Cairo, Egypt.
Department of Nephrology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Int Urol Nephrol. 2019 Sep;51(9):1649-1657. doi: 10.1007/s11255-019-02243-w. Epub 2019 Aug 1.
Oxidative stress, which is most likely a key mediator in the development of cardiovascular disease, is implicated in the progression and deterioration of chronic kidney disease. Patients on hemodialysis exhibit the excessive generation of oxidative stressors, which may also be responsible for the endothelial dysfunction prevalent in these patients. Febuxostat, an inhibitor of xanthine oxidase enzyme, is emerging as a novel drug in the amelioration of oxidative stress status. However, studies regarding its effect among hemodialysis patients are still lacking.
This prospective, block-randomized, double-blinded, placebo-controlled study was carried out to assess the effect of oral 40 mg febuxostat on oxidative stress in hemodialysis patients. In total, fifty-seven eligible patients were randomly assigned to either a drug group or a placebo group for the 2-month study period. Serum malondialdehyde (MDA) and serum superoxide dismutase (SOD) were assessed at baseline and at the end of the study. A correlation analysis between previously reported serum asymmetric dimethylarginine (ADMA), serum MDA and serum SOD was performed.
Febuxostat significantly decreased the serum MDA and significantly increased the serum SOD, while no significant results were observed in the placebo group. A highly positive correlation between the MDA levels and ADMA levels at baseline was noticed in both groups, while there was a highly negative correlation between the SOD levels and ADMA levels at baseline in both groups. A positive correlation between the change in ADMA levels and MDA levels from baseline was observed only in the drug group.
Febuxostat appears to have a direct ameliorating effect on oxidative stress in hemodialysis patients with endothelial dysfunction.
氧化应激很可能是心血管疾病发展的关键介质，它与慢性肾病的进展和恶化有关。接受血液透析的患者表现出氧化应激物的过度产生，这也可能是这些患者普遍存在的内皮功能障碍的原因。黄嘌呤氧化酶抑制剂非布司他作为一种改善氧化应激状态的新型药物正在出现。然而，关于其在血液透析患者中的作用的研究仍然缺乏。
本前瞻性、分块随机、双盲、安慰剂对照研究旨在评估口服 40mg 非布司他对血液透析患者氧化应激的影响。共有 57 名符合条件的患者被随机分配到药物组或安慰剂组，进行为期 2 个月的研究。在基线和研究结束时评估血清丙二醛 (MDA) 和血清超氧化物歧化酶 (SOD)。对先前报道的血清不对称二甲基精氨酸 (ADMA)、血清 MDA 和血清 SOD 之间进行了相关性分析。
非布司他显著降低了血清 MDA，显著增加了血清 SOD，而安慰剂组则没有显著效果。两组在基线时均发现 MDA 水平与 ADMA 水平之间存在高度正相关，而两组在基线时均发现 SOD 水平与 ADMA 水平之间存在高度负相关。仅在药物组中观察到 ADMA 水平从基线的变化与 MDA 水平之间存在正相关。
非布司他似乎对伴有内皮功能障碍的血液透析患者的氧化应激具有直接改善作用。
