Diuretic uptitration with half dose combined ACEI plus ARB better decreases proteinuria than combined ACEI plus ARB uptitration
Diuretic uptitration with half dose combined ACEI plus ARB better decreases proteinuria than combined ACEI plus ARB uptitration
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DOI：
10.1093/ndt/gfp776
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发表时间：
2010-07-01
影响因子：
6.1
通讯作者：
Moranne, Olivier
中科院分区：
文献类型：
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作者：
Esnault, Vincent L. M.;Ekhlas, Amr;Moranne, Olivier
方法。在一项随机、交叉、为期6周的3期对照研究中，我们测试了在ACEI和ARB联合半剂量的基础上增加环状利尿剂是否比在ACEI和ARB联合全剂量上增加利尿剂能更好地降低蛋白尿。18例稳定蛋白尿超过1 g/天的患者在常规降压治疗的基础上，随机接受雷米普利5 mg/天、缬沙坦80 mg/天联合雷米普利5 mg/天、缬沙坦80 mg/天、雷米普利10 mg/天、缬沙坦160 mg/天、雷米普利5 mg/天、缬沙坦80 mg/天联合雷米普利并增加呋塞米剂量。主要终点是三个治疗期结束时两次24小时尿液收集的平均尿蛋白/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）和估计的肾小球滤过率（eGFR）水平。与联合雷米普利5 mg/天、缬沙坦80 mg/天以及增加呋塞米剂量相比，联合雷米普利5 mg/天、缬沙坦80 mg/天，以及联合雷米普利10 mg/天、缬沙坦160 mg/天相比，几何平均尿蛋白/肌酐比值更低。在调整收缩压、舒张压或MAP和24小时尿钠后，这些差异仍然显著，但在调整eGFR后，这些差异不显著。利尿剂剂量的增加并没有增加家庭收缩压低于100 mmHg的测量次数，但导致症状性低血压发作次数的统计学显著增加。对于CKD和高残留蛋白尿患者，在ACEI和ARB联合半剂量的基础上谨慎增加利尿剂剂量比增加到ACEI和ARB联合全剂量更能减少蛋白尿。利尿剂的这种抗蛋白尿作用部分可以通过eGFR降低来解释，这表明血液动力学改变的作用，其长期安全性仍有待解决。
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.