Ruggenenti P, Perna A, Gherardi G, Gaspari F, Benini R, Remuzzi G
Mario Negri Institute for Pharmacological Research, Clinical Research Centre for Rare Diseases Aldo e Cele Daccò, Ranica, Italy.
Lancet. 1998 Oct 17;352(9136):1252-6. doi: 10.1016/s0140-6736(98)04433-x.
The Ramipril Efficacy In Nephropathy (REIN) study found that in patients with chronic nephropathies and proteinuria of 3 g or more per 24 h, ramipril safely reduced the rate of decline of the glomerular filtration rate (GFR) and halved the combined risk of doubling of serum creatinine or end-stage renal failure (ESRF), as compared with placebo plus conventional antihypertensive drugs at the same level of blood pressure control. At the end of the core study patients continued on or shifted to ramipril and were formally enrolled into the REIN follow-up study.
97 patients entered the follow-up study. Patients originally randomised to ramipril continued with the same daily dose (n=51), whereas those originally on placebo plus conventional antihypertensive drugs switched to ramipril after the first visit of the follow-up study (n=46). Ramipril (1.25 to 5.00 mg/day) and conventional antihypertensive therapy were targeted at achieving diastolic blood pressure under 90 mm Hg. The main efficacy variables were GFR decline and ESRF (need for dialysis). Analysis was by intention to treat.
During the follow-up study the mean rate of GFR decline per month decreased from 0.44 (SD 0.54) mL/min per 1.73 m2 in the core study to 0.10 (0.50) mL/min per 1.73 m2 in patients originally randomised to ramipril (p=0.017), and from 0.81 (1.12) to 0.14 (0.87) mL/min per 1.73 m2 in those originally randomised to placebo plus conventional antihypertensive therapy (p=0.017). At the final visit, mean absolute GFR values were 12 mL/min per 1.73 m2 higher (33% better) in patients randomised to ramipril than in those assigned placebo (n=26 and 17, respectively: 35.5 [19.0] vs 23.8 [9.4] mL/min per 1.73 m2, p=0.01). 19 of the patients originally on ramipril versus 35 switched from placebo to ramipril progressed to ESRF (p=0.027) during the whole observation period; of these, six (8%) versus 14 (16%) reached that endpoint during the follow-up study; and the risk ratios were 1.86 (95% CI 1.07-3.26) over the whole observation period and 2.95 (1.13-7.68) during follow-up. Beyond follow-up at month 36, the incidence of ESRF was zero in patients originally randomised to ramipril but 30% in patients on placebo plus conventional antihypertensive therapy.
In patients with chronic nephropathy and high risk of rapid progression to ESRF, ramipril reversed the tendency of GFR to decline with time. Moreover, a treatment period of sufficient duration (> or =36 months) eliminated the need for dialysis. Even patients previously treated with antihypertensive drugs other than angiotensin-converting-enzyme inhibitors benefited from shifting to ramipril.
雷米普利治疗肾病疗效（REIN）研究发现，对于慢性肾病且24小时蛋白尿达3克或更多的患者，与在相同血压控制水平下使用安慰剂加传统抗高血压药物相比，雷米普利能安全降低肾小球滤过率（GFR）的下降速率，并使血清肌酐翻倍或终末期肾衰竭（ESRF）的综合风险减半。在核心研究结束时，患者继续使用雷米普利或改用雷米普利，并正式进入REIN随访研究。
97例患者进入随访研究。最初随机分配至雷米普利组的患者继续使用相同的每日剂量（n = 51），而最初使用安慰剂加传统抗高血压药物的患者在随访研究的首次就诊后改用雷米普利（n = 46）。雷米普利（1.25至5.00毫克/天）和传统抗高血压治疗的目标是使舒张压低于90毫米汞柱。主要疗效变量为GFR下降和ESRF（透析需求）。分析采用意向性治疗。
在随访研究期间，最初随机分配至雷米普利组的患者，其GFR每月平均下降速率从核心研究中的0.44（标准差0.54）毫升/分钟/1.73平方米降至0.10（0.50）毫升/分钟/1.73平方米（p = 0.017）；最初随机分配至安慰剂加传统抗高血压治疗组的患者，其GFR每月平均下降速率从0.81（1.12）降至0.14（0.87）毫升/分钟/1.73平方米（p = 0.017）。在最后一次就诊时，随机分配至雷米普利组的患者的平均绝对GFR值比分配至安慰剂组的患者高12毫升/分钟/1.73平方米（改善33%）（分别为n = 26和17：35.5[19.0]对23.8[9.4]毫升/分钟/1.73平方米，p = 0.01）。在整个观察期内，最初使用雷米普利的患者中有19例进展至ESRF，而从安慰剂改用雷米普利的患者中有35例进展至ESRF（p = 0.027）；其中，在随访研究期间，分别有6例（8%）和14例（16%）达到该终点；整个观察期内的风险比为1.86（95%置信区间1.07 - 3.26），随访期间为2.95（1.13 - 7.68）。在36个月随访之后，最初随机分配至雷米普利组的患者中ESRF发生率为零，而使用安慰剂加传统抗高血压治疗的患者中为30%。
对于有快速进展至ESRF高风险的慢性肾病患者，雷米普利可扭转GFR随时间下降的趋势。此外，足够长的治疗期（≥36个月）可消除透析需求。即使是先前使用过除血管紧张素转换酶抑制剂以外的抗高血压药物的患者，改用雷米普利也有益处。
