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预防糖尿病患者的肾脏并发症:替米沙坦与依那普利对糖尿病患者的影响(DETAIL)研究

Preventing renal complications in diabetic patients: the Diabetics Exposed to Telmisartan And enalaprIL (DETAIL) study.

作者信息

Barnett A H

机构信息

Undergraduate Centre, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, West Midlands, UK.

出版信息

Acta Diabetol. 2005 Apr;42 Suppl 1:S42-9. doi: 10.1007/s00592-005-0180-4.

Abstract

Diabetic nephropathy is characterised by hypertension and persistent proteinuria. If ineffectively controlled, a progressive decline in renal function can result in end-stage renal disease. Patients with diabetic nephropathy are also at greatly increased risk of cardiovascular disease. Angiotensin-converting enzyme (ACE) inhibitors display additional renoprotective effects beyond systemic blood pressure lowering, perhaps due to reduction in intraglomerular pressure by inhibition of angiotensin II activity. In type 2 diabetics, ACE inhibitors have variable effects, with some studies showing a reduction in microalbuminuria, prevention of the progression to macroalbuminuria and maintenance of renal function. Randomised studies have demonstrated that angiotensin II receptor blockers (ARBs), as well as controlling systemic blood pressure, delay progression of proteinuria in patients with diabetic nephropathy. Telmisartan has a number of features that may make it particularly suitable for the treatment of diabetic nephropathy. In addition to its long duration of action and almost exclusive faecal excretion, its high lipophilicity should assist in tissue penetration. The Diabetics Exposed to Telmisartan And enalaprIL (DETAIL) study was designed to compare the long-term renal outcome of treatment with telmisartan 40.80 mg versus enalapril 10.20 mg (with titration to the higher dose after 4 weeks) in patients with type 2 diabetes, mild-to-moderate hypertension and albuminuria. The primary endpoint is the change in glomerular filtration rate after 5 years' randomised treatment. Secondary endpoints are annual changes in glomerular filtration rate, serum creatinine and urinary albumin excretion, as well as incidences of end-stage renal disease, cardiovascular events, all-cause mortality and adverse events. The groundbreaking DETAIL study revealed that telmisartan conferred comparable renoprotection to enalapril and was associated with a low incidence of mortality.

摘要

糖尿病肾病的特征是高血压和持续性蛋白尿。如果控制不佳,肾功能的逐渐下降会导致终末期肾病。糖尿病肾病患者患心血管疾病的风险也会大幅增加。血管紧张素转换酶(ACE)抑制剂除了能降低全身血压外,还具有额外的肾脏保护作用,这可能是由于抑制血管紧张素II活性降低了肾小球内压。在2型糖尿病患者中,ACE抑制剂的效果不一,一些研究表明其可减少微量白蛋白尿、预防进展为大量白蛋白尿并维持肾功能。随机研究表明,血管紧张素II受体阻滞剂(ARB)除了能控制全身血压外,还能延缓糖尿病肾病患者蛋白尿的进展。替米沙坦具有许多特性,可能使其特别适合治疗糖尿病肾病。除了作用时间长且几乎完全经粪便排泄外,其高亲脂性有助于组织渗透。替米沙坦与依那普利治疗2型糖尿病、轻度至中度高血压和白蛋白尿患者的长期肾脏结局比较(DETAIL)研究旨在比较40/80mg替米沙坦与10/20mg依那普利(4周后滴定至更高剂量)治疗的长期肾脏结局。主要终点是随机治疗5年后肾小球滤过率的变化。次要终点是肾小球滤过率、血清肌酐和尿白蛋白排泄的年度变化,以及终末期肾病、心血管事件、全因死亡率和不良事件的发生率。开创性的DETAIL研究表明,替米沙坦给予的肾脏保护作用与依那普利相当,且死亡率较低。

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