Diabetologia. 1996 May;39(5):587-93. doi: 10.1007/BF00403306.
In insulin-dependent diabetes mellitus (IDDM), microalbuminuria predicts renal and cardiovascular disease. We report a combined analysis of 235 normotensive IDDM patients with microalbuminuria who participated in two 24-month double-blind, randomised, placebo-controlled trials to assess the effects of captopril 50 mg twice daily on the progression to overt clinical albuminuria. Of the 225 patients who were evaluable on an intent to treat basis, 25 of 114 placebo-treated patients (21.9%) and 8 or 111 captopril-treated patients (7.2%) progressed to persistent clinical albuminuria. The risk of progression over 24 months was significantly reduced by captopril (p = 0.004) with a risk reduction of 69.2% (95% confidence interval (CI):31.7 to 86.1%). This degree of risk reduction remained at the same level (62.9% [16.1-83.6%], p = 0.017) after adjustment for differences in time-varying mean arterial blood pressure. Albumin excretion rate increased by an average of 14.2% [3.1-26.5%] per year in the placebo-treated group compared with a reduction of 9.6% [-18.6-0.4%] per year in the captopril-treated group (p = 0.002). The rate of fall of creatinine clearance tended to be faster in the placebo-treated group than in the captopril-treated group (-6.4 [-10.2- -2.5] vs -1.4 [-5.3-2.6] ml.min-1.1.73m-2, p = 0.07). Baseline albumin excretion rate (p < 0.0001) and glycated haemoglobin (p = 0.03) were independent predictors of progression to clinical albuminuria and changes in mean arterial blood pressure (p = 0.02) and serum cholesterol level (p = 0.003) were significantly associated with percentage changes in albumin excretion rate. Captopril reduces the risk of progression to overt nephropathy in IDDM patients with microalbuminuria, an effect partly independent of its blood pressure-lowering effects.
在胰岛素依赖型糖尿病(IDDM)中,微量白蛋白尿可预测肾脏和心血管疾病。我们报告了对235例患有微量白蛋白尿的血压正常的IDDM患者进行的综合分析,这些患者参与了两项为期24个月的双盲、随机、安慰剂对照试验,以评估每日两次服用50毫克卡托普利对进展为显性临床白蛋白尿的影响。在按意向性治疗原则可评估的225例患者中,114例接受安慰剂治疗的患者中有25例(21.9%)进展为持续性临床白蛋白尿,111例接受卡托普利治疗的患者中有8例(7.2%)进展为持续性临床白蛋白尿。卡托普利显著降低了24个月内进展的风险(p = 0.004),风险降低了69.2%(95%置信区间(CI):31.7至86.1%)。在对随时间变化的平均动脉血压差异进行调整后,这种风险降低程度保持在同一水平(62.9%[16.1 - 83.6%],p = 0.017)。安慰剂治疗组的白蛋白排泄率平均每年增加14.2%[3.1 - 26.5%],而卡托普利治疗组每年降低9.6%[-18.6 - 0.4%](p = 0.002)。安慰剂治疗组肌酐清除率的下降速度往往比卡托普利治疗组更快(-6.4[-10.2 - -2.5]对-1.4[-5.3 - 2.6]ml.min-1.1.73m-2,p = 0.07)。基线白蛋白排泄率(p < 0.0001)和糖化血红蛋白(p = 0.03)是进展为临床白蛋白尿的独立预测因素,平均动脉血压变化(p = 0.02)和血清胆固醇水平(p = 0.003)与白蛋白排泄率的百分比变化显著相关。卡托普利可降低患有微量白蛋白尿的IDDM患者进展为显性肾病的风险,这一效果部分独立于其降压作用。