血管紧张素转换酶抑制剂和血管紧张素Ⅱ受体拮抗剂单药治疗及联合应用对慢性肾脏病患者肾素-血管紧张素系统表达的影响

Effect of angiotensin converting enzyme inhibitor and angiotensin Ⅱ receptor blocker on renin-angiotensin system in patients with chronic kidney disease

目的:探讨血管紧张素转换酶抑制剂(ACEI)和血管紧张素Ⅱ受体拮抗剂(ARB)单药治疗及联合应用对慢性肾脏病(CKD)患者循环和肾脏局部肾素-血管紧张素系统(RAS)表达的影响及差异。方法:采用前瞻性随机对照设计,将24例CKD患者随机分为贝那普利组、缬沙坦组和联合治疗组,分别予贝那普利20mg/d、缬沙坦160mg/d、贝那普利10mg/d和缬沙坦80mg/d治疗8周。记录随访过程中的血压、血清肌酐(SCr)、尿蛋白定量等临床指标,并采用放射免疫法和酶联免疫吸附法测定血和尿RAS组分,比较治疗前后的临床指标和血、尿RAS组分活性以及三组间的差异。结果:治疗8周后贝那普利组的尿蛋白定量[(0.61±0.25)g/24hvs(0.35±0.20)g/24h,P<0.05]、尿血管紧张素原[(60.76±28.05)ng/(mg·Cr)vs(23.09±14.74)ng/(mg·Cr),P<0.05]低于基线;缬沙坦组的平均动脉压低于基线[(99.17±10.56)mmHgvs(84.63±9.33)mmHg,P<0.05],血浆肾素活性(PRA)高于基线[(1.33±0.76)ng/(ml·h)vs(6.02±2.59)ng/(ml·h),P<0.01]。贝那普利组、缬沙坦组和联合治疗组的主要终点事件发生率(蛋白尿下降>30%)分别为87.5%、12.5%和62.5%,贝那普利组显著高于缬沙坦组(P<0.05)。治疗8周后贝那普利组PRA[(3.20±1.25)ng/(ml·h)vs(6.02±2.59)ng/(ml·h),P<0.05)和血管紧张素Ⅱ浓度[(53.32±11.13)pg/mlvs(105.61±59.49)pg/ml,P<0.05)低于缬沙坦组。结论:贝那普利短期治疗可有效降低CKD患者肾脏局部血管紧张素Ⅱ活性和蛋白尿,而缬沙坦可较贝那普利更显著升高血浆肾素活性和血管紧张素Ⅱ浓度。

Objective：To investigate the effect of angiotensin converting enzyme inhibitor（ACEI）, angiotensinⅡ receptor blocker（ARB） and combined treatment on general and intrarenal renin-angiotensin system（RAS） in pants with chronic kidney disease（CKD）. Methodology：Twenty-four CKD patients were randomly assigned to benazepril, valsartan or conmbined treatment group. During 8 weeks of benazepril treatment （20 rag/d）,valsartan treatment （160 rag/d） or conmbined treatment （benazepril 10 mg/d and valsartan 80 mg/d）,the blood pressure, serum creatinine, and proteinuria were detected, and the plasma renin activity （PRA） , plasma and urinary angiotensinogen （AGT） , angiotensin I[ （Ang U ） and aldosterone were measured by RIA or ELISA. Results： After treatment of 8 weeks, the level of proteinuria [ （0. 61 ± 0. 25） g/24h vs （0. 35 ±0. 20） g/24h,P 〈0. 05] and urinary AGT [ （60.76 ±28. 05） ng/（mg-Cr） vs （23.09 ± 14.74） ng/（ mg. Cr）, P 〈 0. 05 ] was lower in benazepril group than that in baseline. In valsartan group, mean artery pressure was lower than baseline [ （99. 17 ± 10. 56 ） mmHg vs （ 84. 63 ± 9. 33 ） mmHg, P 〈 0. 05 ] and PRA was higher than baseline [ （ 1.33 ±0. 76）ng/（ml·h） vs （6. 02± 2. 59） ng/（ml·h） ,P 〈0. 01 ]. The primary end point was 87.5% in benazeprilgroup, 12. 5% in valsartan group and 62. 5% in combined treatment group. Compared with valsartan, the primary end point was reduced by benazepril （ P 〈 0.05 ）. After 8 weeks treatment, PRA [ （ 3.20 ± 1.25 ）ng/（ ml·h） vs （ 6.02 ± 2. 59 ） rig/（ ml·h ）, P 〈 0. 05 ] and plasma Ang Ⅱ [ （53.32 ± 11.13 ） pg/ml vs （ 105.61 ± 59. 49 ） pg/ml, P 〈 0. 05 ] of benazepril group were lower than those of valsartan group. Conclusion：Short-term treatment with benazepril can reduce intrarenal agiotensin Ⅱactivity and urinary protein in patients with CKD. Valsartan may elevate plasma renin activity and angiotensin U more significantly than benazepril.