Avosentan Reduces Albumin Excretion in Diabetics with Macroalbuminuria

被引:202
作者
Wenzel, Rene R. [1 ]
Littke, Thomas [2 ]
Kuranoff, Susan [2 ]
Juergens, Christiania [3 ]
Bruck, Heike [3 ]
Ritz, Eberhard [4 ]
Philipp, Thomas [3 ]
Mitchell, Anna [3 ]
机构
[1] Paracelsus Univ Salzburg Austria, Acad Teaching Hosp, AO Krankenhaus Zell See, Dept Internal Med, A-5700 Zell Am See, Austria
[2] SPEEDEL Pharma AG, Basel, Switzerland
[3] Univ Hosp Essen, Dept Hypertens & Nephrol, Essen, Germany
[4] Heidelberg Univ, Dept Nephrol, Heidelberg, Germany
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2009年 / 20卷 / 03期
关键词
ENDOTHELIN RECEPTOR ANTAGONISTS; BLOOD-PRESSURE; SODIUM-INTAKE; TYPE-2; NEPHROPATHY; ANGIOTENSIN; PROGRESSION; MELLITUS; PROTEINURIA; INHIBITION;
D O I
10.1681/ASN.2008050482
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:655 / 664
页数:10
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