血管紧张素转换酶抑制剂用于血清肌酐大于266μmol/L的慢性肾脏病患者的研究

Can angiotensin-converting enzyme inhibitor be used in chronic kidney disease patients with serum creatinine level greater than 266 μmol/L?

目的探讨血管紧张素转换酶抑制剂(ACEI)对血肌酐(Scr)>266 μmol/L者的肾脏是否具有保护作用及此类患者服用ACEI的安全性.方法慢性肾脏病患者168例,口服贝那普利10 mg/d,剔除21例咳嗽者,余147例按Scr水平分为A组(Scr 133～265 μmol/L组)和B组(Scr266～442 μmol/L组),B组再分为Ⅰ组和Ⅱ组.A组和Ⅰ组患者口服贝那普利10～20 mg/d,根据血压控制情况加服钙离子拮抗剂和(或)美托洛尔和(或)血管扩张剂.Ⅱ组患者不服贝那普利,服其他降压药物的情况同Ⅰ组.3组降压的靶目标为≤125/75 mm Hg.随访2年,以Scr水平较基线值增加1倍,或需要进入透析治疗作为主要研究终点.结果 (1)平均动脉压的降幅3组间差异无统计学意义 (P>0.05);原有高血压的患者血压达靶目标值的比率A组为59.61%,Ⅰ组为48.97%, Ⅱ组为56.25%(P>0.05).(2)尿蛋白平均降幅A组、Ⅰ组明显高于Ⅱ组;尿蛋白基础值>1.5 g/24 h者用药2年后尿蛋白降至1 g/24 h以下的百分率A组为55.55%,Ⅰ组为52.63%,Ⅱ组为16.66%.(3)A组、Ⅰ组、Ⅱ组2年后达主要终点事件的发生率分别为19.23%、40.90%、51.35%,左心室质量指数、左心室肥厚发生率均较基线值明显下降;3组间心血管事件发生率亦无显著差异.(5) Ⅰ组患者治疗后2个月内Scr增加超过30%的人数及咳嗽、高血钾等副作用的发生率与A组、Ⅱ组相比无明显增加.结论 ACEI对Scr在266～442 μmol/L的慢性肾脏病患者仍有明显的肾脏保护作用,这类患者应用ACEI后副作用的发生率无明显升高.

Objective Angiotensin-converting enzyme inhibitor （ACEI） has been demonstrated to have protective effect for patients with mild to moderate chronic kidney disease （CKD）. However, little evidence is available for the benefit or side-effects of ACEI in treating patients with more severe CKD. A prospective, randomized controlled trial was performed to evaluate the renal protective effect and safety of ACEI in patients whose serum creatinine （Scr） levels were higher than 265 μmol/L. Methods 168 CKD patients took benazepril for two months. 21 patients quitted the trial because of cough. The remaining 147 CKD patients were divided into two groups according to their Scr levels. Patients with Scr 133-265 μmol/L were included in group A （n=55）, and those with Scr 266-442 μmol/L were included in group B （n=92）. Furthermore, group B were divided randomly into two subgroups, B1 （n=47） and B2 （n=45）. Benazepril was given （10-20mg/d） as an intervention for group A and group B1. Additional calciumchannel antagonist and/or [3-blocker and/or vasodilator were used for blood pressure control in those two groups. Patients in group B2 served as controls who take calcium-channel antagonist and/or [3-blocker and/ or vasodilator but not Benazepril. The target blood pressure is 125/75 mm Hg or less in all groups. All patients were followed for two years. Doubling of the baseline Scr level or end-stage renal disease with the need for dialysis was regarded as the major end point of the trial. Results （1） The magnitude of mean arterial pressure reduction was comparable in group A [ （12.90＋3.21） mmHg] ,group B1 [（13.36＋4.27）mmHg] and group B2 [（10.38＋3.85）mmHg]. There was no significant change among them （P〉0.05 in all）. （2）The magnitude of urinary protein reduction （4）in group A [（0.52＋0.29） g/24h],group B1[（0.50＋0.26）g/24h] were much higher than that in group B2 [（0.19＋0.13）g/24h] （P〈0.05） ,but there was no significant difference between group A and BI（P=0.94）. （3） By the end of two years, the percentages of cases reaching the major end point in group A.group B1 and group B2 were 19.23%, 40.90% and 51.35% respectively. There was significant difference among the three groups （X^2=12.14,v=2,P=0.002）. （4） After two years of treatment, the left ventricular mass indexes and the percentages of left ventricular hypertrophy in group A,group B1 and group B2 were all decreased significantly. There were no statistical differences among the three groups. （5） The incidence of ACEI related adverse reactions, such as rapid increase of Scr more than 30%, dry cough or hyperkalemia were not different among the three groups. Conclusions Benazepril slows the progression of CKD in patients with Scr higher than 266μmol/L, it is safe in these patients.