Barnett Anthony
Undergraduate Centre, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, UK.
J Am Soc Nephrol. 2006 Apr;17(4 Suppl 2):S132-5. doi: 10.1681/ASN.2005121326.
Patients with type 2 diabetes are prone to hypertension and persistent protein leakage from the kidney (microalbuminuria or macroalbuminuria). A progressive decline in renal function can lead to overt diabetic nephropathy and ESRD. The likelihood of cardiovascular disease also is increased. Control of hypertension is paramount to prevent these life-threatening complications. Agents that target the renin-angiotensin system--angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers--have been shown to be renoprotective. The groundbreaking Diabetics Exposed to Telmisartan And enalaprIL (DETAIL) trial was designed to address the absence of comparative data on the long-term effects of an angiotensin II receptor blocker versus an angiotensin-converting enzyme inhibitor on renoprotection and survival in 250 patients with hypertension and early type 2 diabetic nephropathy. The primary purpose of the 5-yr double-blind, double-dummy, randomized study was to establish whether 40 to 80 mg of telmisartan conferred similar (i.e., noninferior) renoprotection to 10 to 20 mg of enalapril as determined by the change from baseline in GFR, measured by the plasma clearance of iohexol. Secondary end points included the emergence of ESRD and all-cause mortality. Telmisartan was not inferior to enalapril in reducing the decline in GFR: Mean annual declines in GFR were 3.7 and 3.3 ml/min per 1.73 m(2) with telmisartan and enalapril, respectively. During the 5-yr study period, no patient developed a serum creatinine >200 micromol/L, and none required dialysis. There were only six deaths in each treatment group during the study, with half being due to cardiovascular events.
2型糖尿病患者容易出现高血压和持续性肾脏蛋白渗漏(微量白蛋白尿或大量白蛋白尿)。肾功能的逐渐下降可导致显性糖尿病肾病和终末期肾病。心血管疾病的发生风险也会增加。控制高血压对于预防这些危及生命的并发症至关重要。已证明,作用于肾素-血管紧张素系统的药物——血管紧张素转换酶抑制剂和血管紧张素II受体阻滞剂——具有肾脏保护作用。开创性的替米沙坦与依那普利治疗糖尿病患者(DETAIL)试验旨在解决缺乏关于血管紧张素II受体阻滞剂与血管紧张素转换酶抑制剂对250例高血压合并早期2型糖尿病肾病患者肾脏保护作用和生存的长期影响的比较数据这一问题。这项为期5年的双盲、双模拟、随机研究的主要目的是确定40至80毫克替米沙坦是否能像10至20毫克依那普利一样,通过碘海醇血浆清除率测量的肾小球滤过率(GFR)自基线的变化来提供相似(即非劣效)的肾脏保护作用。次要终点包括终末期肾病的出现和全因死亡率。在降低GFR下降方面,替米沙坦不劣于依那普利:替米沙坦和依那普利治疗组的GFR平均每年下降分别为每1.73平方米3.7和3.3毫升/分钟。在5年的研究期间,没有患者的血清肌酐>200微摩尔/升,也没有人需要透析。研究期间,每个治疗组仅有6例死亡,其中一半死于心血管事件。