Dual renin-angiotensin system blockade at optimal doses for proteinuria
Dual renin-angiotensin system blockade at optimal doses for proteinuria
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DOI：
10.1046/j.1523-1755.2002.00536.x
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发表时间：
2002-09-01
影响因子：
19.6
通讯作者：
dE Zeeuw, D
中科院分区：
文献类型：
--
作者：
Laverman, GD;Navis, G;dE Zeeuw, D
背景将血管紧张素转换酶（ACE）抑制剂赖诺普利和血管紧张素II（Ang II）拮抗剂氯沙坦联合治疗的抗蛋白尿效果与最佳抗蛋白尿剂量的单药治疗进行比较。为此目的，在9名非糖尿病肾病患者中研究了赖诺普利和氯沙坦，这些患者的中位蛋白尿为4.5 g/天（95% CI，3.5，6.4），肌酐清除率为80 mL/ min（95% CI，66，96），平均动脉压（MAP）为102 mm Hg（95% CI，93，112）。首先，在两个方案中，每个剂量的治疗期为6周，在每个患者中确定每种药物的最佳抗蛋白尿剂量。氯沙坦和赖诺普利以随机顺序使用，每种药物之前都有一个基线期，没有药物。氯沙坦的剂量（mg/天）分别为50、100、150和50。赖诺普利剂量分别为10、20、40和10。在第二个方案后，患者接受联合治疗，使用为单个药物建立的最佳抗蛋白尿剂量。氯沙坦100 mg剂量组的抗蛋白尿反应最佳（-46%; 95% CI，-60，-24%），大于50 mg剂量组（-27%; 95% CI，-42，-4%，P < 0.05），但与150 mg剂量组无差异（-46%; 95% CI，-58; -20%）。在赖诺普利的每个剂量上调步骤中，蛋白尿进一步降低至40 mg剂量时的-75%（95%CI，-85，-43%）。联合治疗比氯沙坦单药治疗更有效地减少蛋白尿（-85%，95%CI，-96，-58），但程度低于赖诺普利。在相似剂量下获得最佳血压反应。使用肾素-血管紧张素系统阻滞剂进行剂量滴定，然后进行添加治疗，对于减少蛋白尿非常有效。该方案的安全性需要在未来的研究中加以解决。
Background. The antiproteinuric effect of combining the angiotensin-converting enzyme (ACE) inhibitor lisinopril and the angiotensin II (Ang II) antagonist losartan was compared to that of the optimal antiproteinuric doses of monotherapy.Methods. To this purpose, lisinopril and losartan were studied in 9 nondiabetic renal patients with median proteinuria 4.5 g/day (95% Cl, 3.5, 6.4), creatinine clearance of 80 mL/ min (95% CI, 66, 96), and mean arterial pressure (MAP) of 102 mm Hg (95 % CI, 93, 112). First, in two protocols with six-week treatment periods per dose, the optimal antiproteinuric dose of each drug was established in each patient. Losartan and lisinopril were used in randomized order, each preceded by a baseline period without medication. The doses of losartan (mg/day) were 50, 100, 150, and again 50. The lisinopril doses were 10, 20, 40, and again 10. After the second protocol, patients were treated with a combination, using the optimal antiproteinuric doses established for the individual drugs.Results. The antiproteinuric response by losartan was optimal at 100 mg (-46%; 95% CI, -60, -24%), being larger than at the 50 mg dose (-27%; 95% CI, -42, -4%, P < 0.05), but not different from the 150 mg dose (-46%; 95% CI, -58; -20%). Proteinuria decreased further at each up-titration step of lisinopril to - 75 % (95 % CI, - 85, -43 %) at the 40 mg dose. Combination therapy reduced proteinuria more effectively (-85%; 95% Cl, -96, -58) than monotherapy with losartan, and to a lesser extent than with lisinopril. Optimal blood pressure responses were obtained at similar doses.Conclusions. Dose-titration with a renin-angiotensin system blocker, followed by add-on therapy is highly effective in order to reduce proteinuria. The safety of this regimen needs to be addressed in future studies.