Ye Huizhen, Huo Zhihao, Ye Peiyi, Xiao Guanqing, Zhang Zhe, Xie Chao, Kong Yaozhong
Nephrology Department, The First People's Foshan Hospital, Foshan, Guangdong, China.
PeerJ. 2020 Mar 12;8:e8575. doi: 10.7717/peerj.8575. eCollection 2020.
Both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are blood pressure-lowering agents, but they are also being used to control proteinuria in early chronic kidney disease (CKD) patients. However, clinically, some patients present merely proteinuria without hypertension. No guidelines pointed out how to select treatments for proteinuria in normotensive patients. Thus, we conducted a Bayesian network analysis to evaluate the relative effects of different kinds of ACEI or ARB or their combination on proteinuria and blood pressure reduction.
The protocol was registered in PROSPERO with ID CRD42017073721. A comprehensive literature database query was carried out systematically according to PICOS strategies. The primary outcome was reduction in proteinuria, and the secondary outcomes were eGFR reduction and blood pressure reduction. Random-effects pairwise and Bayesian network meta-analyses were used to estimate the effect of different regimens.
A total of 14 RCTs with 1,098 patients were included in the analysis. All treatment strategies of ACEI, ARB or their combination had significantly greater efficacy in reducing proteinuria than placebo in normotensive CKD patients. The combination therapy of olmesartan+temocapril had the highest probability (22%) of being the most effective treatment to reduce proteinuria in normotensive CKD patients. Olmesartan and lisinopril ranked second (12%), and temocapril ranked third (15%) but reduced blood pressure less than placebo. For IgA nephropathy, the combination therapy of olmesartan+temocapril also had the highest probability (43%) of being the best antiproteinuric treatment, while enalapril had the highest probability (58%) of being the best antiproteinuric therapy for diabetic nephropathy.
The combination therapy of olmesartan plus temocapril appeared to be the most efficacious for reducing proteinuria in normotensive CKD patients and IgA nephropathy, but the clinical application should be balanced against potential harms. Temocapril can be an option when practitioners are searching for more proteinuria reduction but less blood pressure variation. In normotensive diabetic nephropathy, monotherapy with the ACEI enalapril seems to be the most efficacious intervention for reducing albuminuria. Future studies are required to give a more definitive recommendation.
血管紧张素转换酶抑制剂（ACEI）和血管紧张素受体阻滞剂（ARB）均为降压药物，但也用于控制早期慢性肾脏病（CKD）患者的蛋白尿。然而，临床上有些患者仅表现为蛋白尿而无高血压。尚无指南指出如何为血压正常的患者选择蛋白尿的治疗方法。因此，我们进行了一项贝叶斯网络分析，以评估不同种类的ACEI或ARB或其联合用药对蛋白尿减少及血压降低的相对效果。
该方案已在国际前瞻性系统评价注册库（PROSPERO）注册，注册号为CRD42017073721。根据PICOS策略系统地进行全面的文献数据库检索。主要结局为蛋白尿减少，次要结局为估算肾小球滤过率（eGFR）降低和血压降低。采用随机效应成对分析和贝叶斯网络荟萃分析来估计不同治疗方案的效果。
分析共纳入14项随机对照试验（RCT），涉及1098例患者。在血压正常的CKD患者中，ACEI、ARB或其联合用药的所有治疗策略在减少蛋白尿方面均比安慰剂具有显著更高的疗效。奥美沙坦+替莫普利联合治疗在血压正常的CKD患者中成为最有效减少蛋白尿治疗方法的概率最高（22%）。奥美沙坦和赖诺普利并列第二（12%），替莫普利排第三（15%），但降低血压的效果低于安慰剂。对于IgA肾病，奥美沙坦+替莫普利联合治疗成为最佳抗蛋白尿治疗方法的概率也最高（43%），而依那普利在糖尿病肾病中成为最佳抗蛋白尿治疗方法的概率最高（58%）。
奥美沙坦加替莫普利联合治疗在血压正常的CKD患者和IgA肾病患者中似乎是减少蛋白尿最有效的方法，但临床应用时应权衡潜在危害。当医生寻求更多减少蛋白尿但血压变化较小时，替莫普利可以作为一个选择。在血压正常的糖尿病肾病中，使用ACEI依那普利单药治疗似乎是减少蛋白尿最有效的干预措施。需要未来的研究给出更明确的推荐。
