Avosentan Reduces Albumin Excretion in Diabetics with Macroalbuminuria
Avosentan Reduces Albumin Excretion in Diabetics with Macroalbuminuria
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DOI：
10.1681/asn.2008050482
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发表时间：
2009-03-01
影响因子：
13.6
通讯作者：
Mitchell, Anna
中科院分区：
文献类型：
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作者：
Wenzel, Rene R.;Littke, Thomas;Mitchell, Anna
尽管一线使用血管紧张素转换酶抑制剂（ACEIs）和血管紧张素受体阻滞剂（ARBs），但仍有很大的需要来改善糖尿病肾病及其相关心血管事件的预防和进展。内皮素拮抗剂在实验研究中显示出抗炎、抗纤维化和抗蛋白尿的作用。本研究是一项随机、安慰剂对照、双盲、平行设计、剂量范围研究，研究内皮素- a拮抗剂阿沃森坦（SPP301）对糖尿病肾病患者尿白蛋白排泄率（UAER）的影响。我们随机分配286例糖尿病肾病、大量蛋白尿（UAER 0.2 - 5.6 mg/min）和血压< 180/110 mmHg的患者，在标准ACEI/ARB治疗的基础上，给予阿伏生坦（5、10、25和50 mg）或安慰剂12周。与基线相比，与安慰剂（35.5%）相比，所有阿伏替坦剂量均降低了平均相对UAER（- 16.3%至-29.9%）。与安慰剂（12.1%）相比，所有阿伏生坦剂量的中位相对UAER均下降（28.7%至-44.8%）。12周时肌酐清除率和血压不变。主要不良事件为外周水肿（12%），主要为高剂量阿伏生坦（>= 25 mg）；肝酶没有显著升高。21例（7.3%）患者出现不良事件导致停药。总之，在标准ACEI/ARB治疗之外给予内皮素- a拮抗剂阿伏生坦可降低糖尿病肾病和巨量白蛋白尿患者的UAER。
Despite the first-line use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), there is still a large need to improve the prevention and progression of diabetic nephropathy and its associated cardiovascular events. Endothelin antagonists have shown anti-inflammatory, antifibrotic, and antiproteinuric effects in experimental studies. This study was a randomized, placebo-controlled, double-blind, parallel-design, dosage-range study of the effect of the endothelin-A antagonist avosentan (SPP301) on urinary albumin excretion rate (UAER) in patients with diabetic nephropathy. We randomly assigned 286 patients with diabetic nephropathy, macroalbuminuria (UAER 0.2 to 5.6 mg/min), and BP < 180/110 mmHg to 12 wk of avosentan (5, 10, 25, and 50 mg) or placebo, in addition to standard ACEI/ARB therapy. Relative to baseline, all avosentan dosages decreased mean relative UAER (-16.3 to -29.9%) compared with placebo (35.5%). Median relative UAER decreased with all avosentan dosages (28.7 to -44.8%) compared with placebo (12.1%). Creatinine clearance and BP were unchanged at 12 wk. The main adverse events were peripheral edema (12%), mainly with high (>= 25 mg) dosages of avosentan; significant increases in liver enzymes did not occur. Twenty-one (7.3%) patients experienced adverse events that led to withdrawal from study medication. In summary, the endothelin-A antagonist avosentan given in addition to standard ACEI/ARB treatment decreases UAER in patients with diabetic nephropathy and macroalbuminuria.