血管紧张素II受体阻滞剂对1型糖尿病肾病患者的肾脏保护作用。

Renoprotective effects of angiotensin II receptor blockade in type 1 diabetic patients with diabetic nephropathy.

作者信息

Andersen S, Tarnow L, Rossing P, Hansen B V, Parving H H

机构信息

Steno Diabetes Center, Copenhagen, Denmark.

出版信息

Kidney Int. 2000 Feb;57(2):601-6. doi: 10.1046/j.1523-1755.2000.00880.x.

DOI:10.1046/j.1523-1755.2000.00880.x

PMID:10652037

Abstract

BACKGROUND

Angiotensin I-converting enzyme (ACE) inhibitors reduce angiotensin II formation and induce bradykinin accumulation. Animal studies suggest that bradykinin may play a role for the effects of ACE inhibition on blood pressure and kidney function. Therefore, we compared the renal and hemodynamic effects of specific intervention in the renin-angiotensin system by blockade of the angiotensin II subtype-1 receptor to the effect of ACE inhibition.

METHODS

A randomized, double-blind, cross-over trial was performed in 16 type 1 diabetic patients (10 men), age 42 +/- 2 years (mean +/- SEM). The study consisted of five periods, each lasting two months. The patients received losartan 50 mg, losartan 100 mg, enalapril 10 mg, enalapril 20 mg, and placebo in random order. At the end of each period, albuminuria, 24-hour blood pressure, and glomerular filtration rate (GFR) were determined.

RESULTS

Both doses of losartan and enalapril reduced albuminuria (P < 0.05) and mean arterial blood pressure (MABP; P < 0.05), whereas GFR remained stable. Albuminuria was reduced by 33% (95% CI, 12 to 51) on losartan 50 mg, 44% (95% CI, 26 to 57) on losartan 100 mg, 45% (95% CI, 23 to 61) on enalapril 10 mg, and 59% (95% CI, 39 to 72) on enalapril 20 mg, and MABP fell by 9 +/- 2, 8 +/- 2, 6 +/- 3, and 11 +/- 3 mm Hg (mean +/- SEM), respectively. No significant differences were found between the effects of losartan 100 mg and enalapril 20 mg. HbA1C and sodium intake remained unchanged throughout the study, whereas a significant rise in serum potassium occurred during ACE inhibition.

CONCLUSION

The angiotensin II subtype 1 receptor antagonist, losartan, reduces albuminuria and MABP similar to the effect of ACE inhibition. These results indicate that the reduction in albuminuria and blood pressure during ACE inhibition is primarily caused by interference in the renin-angiotensin system. Our study suggest that losartan represents a valuable new drug in the treatment of hypertension and proteinuria in type 1 diabetic patients with diabetic nephropathy.

摘要

背景

血管紧张素I转换酶（ACE）抑制剂可减少血管紧张素II的形成并促使缓激肽蓄积。动物研究表明，缓激肽可能在ACE抑制对血压和肾功能的作用中发挥作用。因此，我们比较了通过阻断血管紧张素II 1型受体对肾素-血管紧张素系统进行特异性干预与ACE抑制的肾脏和血流动力学效应。

方法

对16例1型糖尿病患者（10例男性）进行了一项随机、双盲、交叉试验，患者年龄为42±2岁（均值±标准误）。该研究包括五个阶段，每个阶段持续两个月。患者随机接受氯沙坦50 mg、氯沙坦100 mg、依那普利10 mg、依那普利20 mg和安慰剂治疗。在每个阶段结束时，测定蛋白尿、24小时血压和肾小球滤过率（GFR）。

结果

氯沙坦和依那普利的两种剂量均降低了蛋白尿（P<0.05）和平均动脉压（MABP；P<0.05），而GFR保持稳定。氯沙坦50 mg使蛋白尿降低33%（95%CI，12%至51%），氯沙坦100 mg使蛋白尿降低44%（95%CI，26%至57%），依那普利10 mg使蛋白尿降低45%（95%CI，23%至61%），依那普利20 mg使蛋白尿降低59%（95%CI，39%至72%），MABP分别下降9±2、8±2、6±3和11±3 mmHg（均值±标准误）。氯沙坦100 mg与依那普利20 mg的效应之间未发现显著差异。在整个研究过程中，糖化血红蛋白（HbA1C）和钠摄入量保持不变，而在ACE抑制期间血清钾显著升高。