Ruggenenti P, Perna A, Gherardi G, Garini G, Zoccali C, Salvadori M, Scolari F, Schena F P, Remuzzi G
Mario Negri Institute for Pharmacological Research, Clinical Research Centre for Rare Diseases, Aldo e Cele Dacco Villa Camozzi, Ranica, Bergamo, Italy.
Lancet. 1999 Jul 31;354(9176):359-64. doi: 10.1016/S0140-6736(98)10363-X.
Stratum 2 of the Ramipril Efficacy in Nephropathy (REIN) study has already shown that in patients with chronic nephropathies and proteinuria of 3 g or more per 24 h, angiotensin-converting enzyme (ACE) inhibition reduced the rate of decline in glomerular filtration and halved the combined risk of doubling of serum creatinine or end-stage renal failure (ESRF) found in controls on placebo plus conventional antihypertensives. In REIN stratum 1, reported here, 24 h proteinuria was 1 g or more but less than 3 g per 24 h.
In stratum 1 of this double-blind trial 186 patients were randomised to a ramipril or a control (placebo plus conventional antihypertensive therapy) group targeted at achieving a diastolic blood pressure of less than 90 mm Hg. The primary endpoints were change in glomerular filtration rate (GFR) and time to ESRF or overt proteinuria (> or =53 g/24 h). Median follow-up was 31 months.
The decline in GFR per month was not significantly different (ramipril 0.26 [SE 0.05] mL per min per 1.73m2, control 0.29 [0.06]). Progression to ESRF was significantly less common in the ramipril group (9/99 vs 18/87) for a relative risk (RR) of 2.72 (95% CI 1.22-6.08); so was progression to overt proteinuria (15/99 vs 27/87, RR 2.40 [1.27-4.52]). Patients with a baseline GFR of 45 mL/min/1.73 m2 or less and proteinuria of 1.5 g/24 h or more had more rapid progression and gained the most from ramipril treatment. Proteinuria decreased by 13% in the ramipril group and increased by 15% in the controls. Cardiovascular events were similar. As expected, the rate of decline in GFR and the frequency of ESRF were much lower in stratum 1 than they had been in stratum 2.
In non-diabetic nephropathies, ACE inhibition confers renoprotection even to patients with non-nephrotic proteinuria.
雷米普利治疗肾病疗效研究（REIN）的第2组已表明，对于慢性肾病且24小时蛋白尿≥3g的患者，血管紧张素转换酶（ACE）抑制可降低肾小球滤过率下降速度，并使安慰剂加传统抗高血压药物治疗的对照组中血清肌酐翻倍或终末期肾衰竭（ESRF）的联合风险减半。在本文报告的REIN第1组中，24小时蛋白尿为≥1g但＜3g/24小时。
在这项双盲试验的第1组中，186例患者被随机分为雷米普利组或对照组（安慰剂加传统抗高血压治疗），目标是使舒张压＜90mmHg。主要终点为肾小球滤过率（GFR）变化以及达到ESRF或显性蛋白尿（≥53g/24小时）的时间。中位随访时间为31个月。
每月GFR下降无显著差异（雷米普利组为0.26[标准误0.05]mL/分钟/1.73m²，对照组为0.29[0.06]）。雷米普利组进展至ESRF的情况显著较少见（9/99比18/87），相对风险（RR）为2.72（95%可信区间1.22 - 6.08）；进展至显性蛋白尿的情况也是如此（15/99比27/87，RR 2.40[1.27 - 4.52]）。基线GFR≤45mL/分钟/1.73m²且蛋白尿≥1.5g/24小时的患者进展更快，从雷米普利治疗中获益最多。雷米普利组蛋白尿下降了13%，而对照组增加了15%。心血管事件相似。正如预期的那样，第1组中GFR下降率和ESRF发生率远低于第2组。
在非糖尿病肾病中，ACE抑制即使对非肾病性蛋白尿患者也具有肾脏保护作用。
