A Randomized Controlled Trial of the Effects of Febuxostat Therapy on Adipokines and Markers of Kidney Fibrosis in Asymptomatic Hyperuricemic Patients With Diabetic Nephropathy.
A Randomized Controlled Trial of the Effects of Febuxostat Therapy on Adipokines and Markers of Kidney Fibrosis in Asymptomatic Hyperuricemic Patients With Diabetic Nephropathy.
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DOI：
10.1177/2054358116675343
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发表时间：
2016
影响因子：
1.7
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Beddhu S;Filipowicz R;Wang B;Wei G;Chen X;Roy AC;DuVall SL;Farrukh H;Habib AN;Bjordahl T;Simmons DL;Munger M;Stoddard G;Kohan DE;Greene T;Huang Y
在观察性研究中，较高的尿酸水平与代谢综合征、糖尿病和肾脏疾病有关。这项研究的目的是研究黄嘌呤氧化还原酶抑制剂非布索他汀降低血浆尿酸是否影响脂肪组织氧化应激、脂肪因子和全身炎症或肾脏纤维化的标志物。这是一项双盲随机对照试验。使用了学术大学的背景。超重或肥胖的成人高尿酸血症和2型糖尿病肾病包括在内。主要终点为脂肪组织硫代巴比妥酸还原物质、脂联素浓度和尿转化生长因子-β(转化生长因子-β)。血浆C-反应蛋白、高分子脂联素、白介素6、肿瘤坏死因子-α、总胆红素和蛋白尿是预先确定的次要终点。参与者被随机分配到非布索他汀组(n=40)或匹配的安慰剂组(n=40)，并跟踪观察24周。基线血浆尿酸水平为426±83微克分子/L；95%完成研究。估计肾小球滤过率(EGFR)从基线时的54±17毫升/分钟/1.73平方米下降到24周时的51±17毫升/分钟/1.73平方米(P=0.05)。在不同的混合效应模型中，与安慰剂相比，非布司坦降低了50%的尿酸(P<；.001)，但对皮下脂肪组织总胆红素(−7.4%，95%可信区间[CI]，57.4%-101.4%)或脂联素(6.7%，95%CI，26.0%-53.8%)水平或尿转化生长因子-β/肌酐比率(18.0%，95%CI，10.0%-54.8%)或次要终点没有显著影响。样本量相对适中，随访持续时间较短。在进展性糖尿病肾病患者中，非布索他可有效降低血尿酸。然而，对于预先指定的主要或次要终点没有观察到可检测到的影响。这项研究已在临床试验网站上注册(NCT01350388)。
In observational studies, higher uric acid levels are associated with metabolic syndrome, diabetes, and kidney disease. The objective of this study is to examine whether reduction of plasma uric acid with febuxostat, a xanthine oxido reductase inhibitor, impacts adipose tissue oxidative stress, adipokines, and markers of systemic inflammation or kidney fibrosis. This was a double-blinded randomized controlled trial. Academic university setting was used. Overweight or obese adults with hyperuricemia and type 2 diabetic nephropathy were included. Adipose tissue thiobarbituric acid reducing substances (TBARS) and adiponectin concentrations and urinary transforming growth factor–β (TGF-β) were primary endpoints. Plasma C-reactive protein, high molecular weight–adiponectin, interleukin–6, tumor necrosis factor–α, and TBARS and albuminuria were among predefined secondary endpoints. Participants were randomly assigned to febuxostat (n = 40) or matching placebo (n = 40) and followed for 24 weeks. Baseline plasma uric acid levels were 426 ± 83 µmol/L; 95% completed the study. Estimated glomerular filtration rate (eGFR) declined from 54 ± 17 mL/min/1.73 m2 at baseline to 51 ± 17 mL/min/1.73 m2 at 24 weeks (P = .05). In separate mixed-effects models, compared with placebo, febuxostat reduced uric acid by 50% (P < .001) but had no significant effects on subcutaneous adipose tissue TBARS (−7.4%, 95% confidence interval [CI], 57.4%-101.4%) or adiponectin (6.7%, 95% CI, 26.0%-53.8%) levels or urinary TGF-β/creatinine ratio (18.0%, 95% CI, 10.0%-54.8%) or secondary endpoints. Relatively modest sample size and short duration of follow-up. In this population with progressive diabetic nephropathy, febuxostat effectively reduced plasma uric acid. However, no detectable effects were observed for the prespecified primary or secondary endpoints. The study was registered in clinicaltrials.gov (NCT01350388).