Department of Medicine, Misato Junshin General Hospital, 745 Kobo, Misato-shi, Saitama 341-0026, Japan Tel. +81-489-53-1321; Fax +81-489-52-7279, JP.
Clin Exp Nephrol. 2002 Sep;6(3):135-9. doi: 10.1007/s101570200023.
Background. Angiotensin (AT)-converting enzyme inhibitors (ACEIs) and AT1-receptor blockers (ARBs) are widely used to reduce urinary albumin excretion (UAE) and slow the progression of diabetic nephropathy. The aim of the present study was to determine whether treatment with trandolapril (an ACEI) and candesartan cilexetil (an ARB) in combination has more effect on UAE and urinary endothelin (ET)-1 excretion than treatment with trandolapril or candesartan cilexetil alone in patients with type 2 diabetes. Methods. Sixty normotensive type 2 diabetes patients with microalbuminuria were randomly assigned to four treatment groups: (A) treatreatment with trandolapril at 2 mg/day (n = 15), (B) treatment with candesartan cilexetil at 8 mg/day (n = 15), (C) treatment with trandolapril at 2 mg/day and candesartan cilexetil at 8 mg/day (n = 15), and (D) treatment with placebo (n = 15). The study period was 18 months. UAE, urinary ET-1, and plasma ET-1 levels were measured in the patients before treatment and after 12 and 18 months of treatment. Results. Before treatment, UAE, urinary ET-1, and plasma ET-1 levels differed little between the four groups. Trandolapril and candesartan cilexetil administered alone reduced UAE and urinary ET-1 excretion to a similar extent (12 months; P < 0.05 and 18 months; P < 0.01). When trandolapril and candesartan cilexetil were coadministered, UAE and urinary ET-1 excretion decreased to a significantly greater extent at 12 and 18 months (P < 0.05) than with trandolapril or candesartan cilexetil alone. However, plasma ET-1 and systemic blood pressure levels were not affected. Conclusions. The data suggest that combination therapy with trandolapril and candesartan cilexetil has an additive effect on the reduction of microalbuminuria in microalbuminuric normotensive type 2 diabetes patients.
背景。血管紧张素转换酶抑制剂（ACEI）和血管紧张素 II 受体阻滞剂（ARB）被广泛用于降低尿白蛋白排泄率（UAE）和减缓糖尿病肾病的进展。本研究的目的是确定在伴有微量白蛋白尿的 2 型糖尿病患者中，与单独使用trandolapril（ACEI）和坎地沙坦西酯（ARB）相比，trandolapril 和坎地沙坦西酯联合治疗对 UAE 和尿内皮素（ET）-1 排泄的影响是否更大。
方法。60 例血压正常的 2 型糖尿病伴微量白蛋白尿患者被随机分为四组：（A）trandolapril 2mg/天治疗组（n=15），（B）坎地沙坦西酯 8mg/天治疗组（n=15），（C）trandolapril 2mg/天和坎地沙坦西酯 8mg/天联合治疗组（n=15），（D）安慰剂治疗组（n=15）。研究时间为 18 个月。在治疗前和治疗 12 个月和 18 个月后测量患者的 UAE、尿 ET-1 和血浆 ET-1 水平。
结果。治疗前，四组间 UAE、尿 ET-1 和血浆 ET-1 水平差异较小。单独使用trandolapril 和坎地沙坦西酯均可使 UAE 和尿 ET-1 排泄量在 12 个月时（P <0.05）和 18 个月时（P <0.01）显著减少。trandolapril 和坎地沙坦西酯联合使用时，12 个月和 18 个月时 UAE 和尿 ET-1 排泄量显著降低（P <0.05），而与单独使用 trandolapril 或坎地沙坦西酯相比。然而，血浆 ET-1 和全身血压水平不受影响。
结论。数据表明，trandolapril 和坎地沙坦西酯联合治疗对伴有微量白蛋白尿的 2 型糖尿病患者微量白蛋白尿的降低具有附加作用。
