Toto R D, Adams-Huet B, Fenves A Z, Mitchell H C, Mulcahy W, Smith R D
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 75235-8856, USA.
Am J Kidney Dis. 1996 Dec;28(6):832-40. doi: 10.1016/s0272-6386(96)90382-0.
Angiotensin-converting enzyme inhibitors reduce proteinuria in both normotensive and hypertensive patients with proteinuric renal disease. However, the mechanism of the antiproteinuric effect has not been clarified. We performed a prospective, double-blind, placebo-controlled, randomized crossover trial to test the hypothesis that the antiproteinuric effect of ramipril was due to an improvement in glomerular permselectivity independent of blood pressure and glomerular filtration rate. The effect of low-dose (1.25 mg/d) and high-dose (5 mg/d) ramipril was assessed in 15 normotensive nondiabetic patients with proteinuria (> 150 mg/d). The study was divided into four 12-week periods: placebo, high- or low-dose ramipril, crossover to low- or high-dose ramipril, and placebo. Blood pressure, glomerular filtration rate, renal plasma flow rate, urinary protein excretion rate, and plasma angiotensin II levels were measured at the end of each period. Mean arterial pressure, urine protein to creatinine ratio, and albumin excretion rate decreased significantly during low- and high-dose ramipril. Glomerular filtration rate and renal plasma flow rate were not changed significantly. Plasma angiotensin II levels decreased with both low- and high-dose ramipril. There were no episodes of hypotension and only one subject developed cough during ramipril that did not require discontinuation of the study drug. In conclusion, administration of ramipril in both low and high doses lowered blood pressure and reduced proteinuria in this cohort of normotensive patients with a variety of proteinuric renal diseases. The antiproteinuric effect of ramipril is probably mediated by a reduction in glomerular capillary pressure.
血管紧张素转换酶抑制剂可降低患有蛋白尿性肾病的血压正常和高血压患者的蛋白尿。然而，其抗蛋白尿作用的机制尚未阐明。我们进行了一项前瞻性、双盲、安慰剂对照、随机交叉试验，以检验雷米普利的抗蛋白尿作用是否归因于肾小球滤过选择性的改善，且该作用独立于血压和肾小球滤过率。在15名血压正常的非糖尿病蛋白尿患者（>150mg/d）中评估了低剂量（1.25mg/d）和高剂量（5mg/d）雷米普利的效果。该研究分为四个12周的阶段：安慰剂、高剂量或低剂量雷米普利、交叉至低剂量或高剂量雷米普利以及安慰剂。在每个阶段结束时测量血压、肾小球滤过率、肾血浆流量、尿蛋白排泄率和血浆血管紧张素II水平。在低剂量和高剂量雷米普利治疗期间，平均动脉压、尿蛋白与肌酐比值和白蛋白排泄率均显著下降。肾小球滤过率和肾血浆流量无显著变化。低剂量和高剂量雷米普利均使血浆血管紧张素II水平下降。未出现低血压发作，在服用雷米普利期间只有一名受试者出现咳嗽，但无需停用研究药物。总之，在这组患有各种蛋白尿性肾病的血压正常患者中，低剂量和高剂量雷米普利均可降低血压并减少蛋白尿。雷米普利的抗蛋白尿作用可能是通过降低肾小球毛细血管压力介导的。
