Diuretic uptitration with half dose combined ACEI + ARB better decreases proteinuria than combined ACEI + ARB uptitration.
Diuretic uptitration with half dose combined ACEI + ARB better decreases proteinuria than combined ACEI + ARB uptitration.
复制标题
半剂量联合 ACEI ARB 利尿上调比联合 ACEI ARB 上调更好地降低蛋白尿。
DOI：
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发表时间：
2010
影响因子：
--
通讯作者：
O. Moranne
中科院分区：
文献类型：
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作者：
V. Esnault;A. Ekhlas;J. Nguyen;O. Moranne
背景
残余蛋白尿是肾衰竭进展的一个强的可改变的危险因素。我们先前研究表明，半剂量血管紧张素转换酶抑制剂（ACEI）和血管紧张素受体阻滞剂（ARB）联合应用的抗蛋白尿作用随利尿剂剂量的增加而增强。方法.我们在一项为期6周的随机、交叉、三个阶段的对照研究中，测试了在ACEI和ARB联合半剂量的基础上增加袢利尿剂的剂量是否比增加ACEI和ARB联合全剂量更能减少蛋白尿。18例稳定蛋白尿超过1 g/天的患者，除常规降压治疗外，还接受雷米普利5 mg/天和缬沙坦80 mg/天联合治疗，随机接受雷米普利5 mg/天和缬沙坦80 mg/天联合治疗，或雷米普利10 mg/天和缬沙坦160 mg/天联合治疗，或雷米普利5 mg/天联合治疗，缬沙坦80 mg/天，并随机增加呋塞米剂量。主要终点是三个治疗期结束时两次24小时尿液采集的平均尿蛋白/肌酐比值。次要终点包括平均24小时蛋白尿、家庭收缩压（SBP）、舒张压（DBP）、平均动脉压（MAP）和估计肾小球滤过率（eGFR）水平。
结果
与雷米普利5 mg/天和缬沙坦80 mg/天的联合用药相比，雷米普利5 mg/天、缬沙坦80 mg/天和增加速尿剂量的联合用药的几何平均尿蛋白/肌酸酐比较低，但也低于雷米普利10 mg/天和缬沙坦160 mg/天的联合用药。在校正SBP、DBP或MAP和24小时尿钠排泄后，这些差异仍然显著，但在校正eGFR后则不显著。利尿剂剂量上调并未增加家庭收缩压测量值低于100 mmHg的数量，但导致症状性低血压发作数量统计学显著增加。
结论
对于CKD和高残余蛋白尿患者，在ACEI和ARB联合使用的一半剂量基础上谨慎上调袢利尿剂剂量比上调至ACEI和ARB联合使用的全剂量更能降低蛋白尿。利尿剂的这种抗蛋白尿作用部分由eGFR降低解释，表明血液动力学改变的作用，其长期安全性仍需解决。
BACKGROUND
Residual proteinuria is a strong modifiable risk factor for renal failure progression. We previously showed that the antiproteinuric effect of combined half doses of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) is increased by raising diuretic dosage. Methods. We tested whether uptitration of loop diuretics on top of combined half doses of ACEI and ARB would better decrease proteinuria than uptitration to combined full doses of ACEI and ARB in a randomized, crossover, three periods of 6-week controlled study. Eighteen patients with stable proteinuria over 1 g/day with combined ramipril at 5 mg/day and valsartan at 80 mg/day in addition to conventional antihypertensive treatments were randomized to receive combined ramipril at 5 mg/day and valsartan at 80 mg/day, or combined ramipril at 10 mg/day and valsartan at 160 mg/day, or combined ramipril at 5 mg/day, valsartan at 80 mg/day and increased furosemide dosage in random order. The primary end point was the mean urinary protein/creatinine ratio in two 24-hour urine collections at the end of the three treatment periods. Secondary end points included mean 24-hour proteinuria, home systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP) and estimated glomerular filtration rate (eGFR) levels.
RESULTS
The geometric mean urinary protein/creatinine ratio was lower with combined ramipril at 5 mg/day, valsartan at 80 mg/day and increased furosemide dosage compared to combined ramipril at 5 mg/day and valsartan at 80 mg/day, but also to combined ramipril at 10 mg/day and valsartan at 160 mg/day. These differences remained significant after adjustment for SBP, DBP or MAP and 24-hour natriuresis but not after adjustment on eGFR. Diuretic dosage uptitration did not increase the number of home systolic blood pressure measurements below 100 mmHg, but led to a statistically significant increase in the number of symptomatic hypotension episodes.
CONCLUSIONS
A cautious uptitration of loop diuretic dosage in addition to combined half doses of ACEI and ARB better decrease proteinuria in patients with CKD and high residual proteinuria than uptitration to full dose of combined ACEI and ARB. This antiproteinuric effect of diuretics was partly explained by an eGFR decrease, suggesting the contribution of haemodynamic modifications, whose safety on the long term still need to be addressed.
DOI：
10.2215/cjn.00600206
发表时间：
2006-07-01
影响因子：
9.8
作者：
Stevens, Lesley A.;Greene, Tom;Levey, Andrew S.
通讯作者：
Levey, Andrew S.