别嘌醇能改善高尿酸血症患者的内皮细胞功能和肾小球滤过率

译者：张文静 校对：马丹 审核：张莉芸

Abstract: Endothelial dysfunction is an early manifestation of vascular injury and contributes to the development of atherosclerotic cardiovascular disease. Recent studies have implicated hyperuricemia as a risk factor for cardiovascular disease. We hypothesized that lowering uric acid in subjects with asymptomatic hyperuricemia with allopurinol might improve endothelial dysfunction, BP, estimated GFR (eGFR), and inflammatory markers. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Subjects with asymptomatic hyperuricemia and no history of gout and 30 normouricemic control subjects were enrolled in this 4-month randomized prospective study. Thirty hyperuricemic patients received 300 mg/d allopurinol and were compared with 37 hyperuricemic patients and 30 normouricemic subjects in matched control groups. Flow-mediated dilation (FMD), eGFR, ambulatory BP monitoring, spot urine protein-creatine ratio, and highly sensitive C-reactive protein were measured at -line and at 4 months. RESULTS: Age, gender, lipid profile, eGFR, hemoglobin, glucose, and level of proteinuria were similar in hyperuricemic subjects and controls at -line. As expected, hyperuricemic patients had higher levels of highly sensitive C-reactive protein and lower FMD compared with normouricemic patients. Allopurinol treatment resulted in a decrease in serum uric acid, a decrease in systolic BP, an increase in FMD, and an increase in eGFR compared with -line. No significant difference was observed in the control hyperuricemic and normouricemic groups. In a multiple regression analysis, FMD levels were independently related to uric acid both before (beta = -0.55) and after (beta =-0.40) treatment. CONCLUSIONS: Treatment of hyperuricemia with allopurinol improves endothelial dysfunction and eGFR in subjects with asymptomatic hyperuricemia.

摘要：内皮细胞功能障碍是血管损伤的早期表现，可导致动脉粥样硬化性心血管疾病的发生。最近的研究显示，高尿酸血症是发生心血管疾病的危险因素。我们推测无症状性高尿酸血症患者使用别嘌醇降低尿酸的同时，可改善内皮细胞功能、血压、估测肾小球滤过率(eGFR)及炎性标志物。方法：纳入无痛风病史的无症状性高尿酸血症患者和30例血尿酸正常对照者，进行一项为期4个月的随机前瞻性研究。30例高尿酸血症患者接受别嘌醇治疗(300 mg/d)，将37例高尿酸血症患者和30例血尿酸正常者作为对照组。在基线和4个月时测定血流介导血管舒张(FMD)、eGFR、动态血压、尿蛋白-肌酐比值和超敏C反应蛋白。结果：基线时高尿酸血症组和对照组在年龄、性别、脂质、eGFR、血红蛋白、血糖和尿蛋白水平是相似的。与正常血尿酸组比较，高尿酸血症患者有较高的超敏C反应蛋白和较低的FMD。与基线相比，使用别嘌醇治疗的高尿酸血症组患者血尿酸降低、收缩压降低、FMD增高以及eGFR增高。而高尿酸血症组和正常血尿酸组之间比较无显著差异。多元回归分析证实FMD水平与血尿酸水平在治疗前后均是独立相关的(治疗前beta= -0.55，治疗后 beta= -0.40)。结论:别嘌醇可改善无症状性高尿酸血症患者的内皮细胞功能和eGFR。

引自：Kanbay M, Huddam B, Azak A, Solak Y, Kadioglu GK, Kirbas I, Duranay M, Covic A, Johnson RJA randomized study of allopurinol on endothelial function and estimated glomular filtration rate in asymptomatic hyperuricemic subjects with normal renal function. Clin Am Soc Nephrol. 2011 Aug;6(8):1887-1894.