Moderate dietary sodium restriction added to angiotensin converting enzyme inhibition compared with dual blockade in lowering proteinuria and blood pressure: randomised controlled trial.
Moderate dietary sodium restriction added to angiotensin converting enzyme inhibition compared with dual blockade in lowering proteinuria and blood pressure: randomised controlled trial.
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DOI：
10.1136/bmj.d4366
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发表时间：
2011-07-26
期刊：
影响因子：
--
通讯作者：
HOlland NEphrology STudy Group
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文献类型：
--
作者：
Slagman MC;Waanders F;Hemmelder MH;Woittiez AJ;Janssen WM;Lambers Heerspink HJ;Navis G;Laverman GD;HOlland NEphrology STudy Group
目的比较非糖尿病肾病患者在接受血管紧张素转换酶（ACE）抑制背景治疗时，加最大剂量限钠或血管紧张素受体阻断或两者联合用药对蛋白尿和血压的影响。设计多中心交叉随机对照试验。在荷兰设立门诊诊所。受试者为52例非糖尿病肾病患者。所有患者在4个6周的时间内随机接受血管紧张素受体阻滞剂（缬沙坦320 mg/天）或安慰剂治疗，在整个研究期间，每种治疗均连续结合低钠饮食（目标50 mmol Na+/天）和常规钠饮食（目标200 mmol Na+/天），并伴有ACE抑制背景（莱诺普利40 mg/天）。药物干预是双盲的；饮食干预是开放标签的。主要结局指标主要结局指标为蛋白尿；次要结局指标是血压。结果低钠饮食组平均尿钠排泄量为106 (SE 5) mmol Na+/天，常规钠饮食组平均尿钠排泄量为184 (SE 6) mmol Na+/天（P<0.001）。在ACE抑制加上常规钠饮食期间，几何平均残余蛋白尿为1.68(95%置信区间1.31至2.14)g/天。在ACE抑制的基础上添加血管紧张素受体阻断剂可使蛋白尿减少至1.44 (1.07 ~ 1.93)g/天（P=0.003），添加低钠饮食可使蛋白尿减少至0.85 (0.66 ~ 1.10)g/天（P<0.001），添加血管紧张素受体阻断剂加低钠饮食可使蛋白尿减少至0.67 (0.50 ~ 0.91)g/天（P<0.001）。在ACE抑制中加入低钠饮食对蛋白尿的减少（51%，95%置信区间为43%至58%）显著大于在ACE抑制中加入血管紧张素受体阻断剂对蛋白尿的减少（21%，8%至32%），与在ACE抑制中加入血管紧张素受体阻断剂和低钠饮食对蛋白尿的减少（62%，53%至70%）相当（P=0.009，经Bonferroni校正后不显著）。在ACE抑制加上常规钠饮食期间，平均收缩压为134 (3)mm Hg。加入血管紧张素受体阻断剂后，平均收缩压没有显著改变(131 (3)mm Hg；P=0.12)，但添加低钠饮食后降低(123 (2)mm Hg；P<0.001)和血管紧张素受体阻断加低钠饮食(121 (3)mm Hg；P<0.001)。低钠饮食（7% (SE 1%)）对收缩压的降低明显大于血管紧张素受体阻断剂（2%(1)）对收缩压的降低（P=0.003），与血管紧张素受体阻断剂和低钠饮食（9%(1)）对ACE抑制的收缩压降低（P=0.14）相似。结论：在非糖尿病肾病患者中，将饮食钠限制到指南推荐的水平比双重阻断治疗更有效地降低蛋白尿和血压。研究结果支持患者和卫生专业人员共同努力减少钠摄入量。试验注册荷兰试验注册NTR675。
Objective To compare the effects on proteinuria and blood pressure of addition of dietary sodium restriction or angiotensin receptor blockade at maximum dose, or their combination, in patients with non-diabetic nephropathy receiving background treatment with angiotensin converting enzyme (ACE) inhibition at maximum dose. Design Multicentre crossover randomised controlled trial. Setting Outpatient clinics in the Netherlands. Participants 52 patients with non-diabetic nephropathy. Interventions All patients were treated during four 6 week periods, in random order, with angiotensin receptor blockade (valsartan 320 mg/day) or placebo, each combined with, consecutively, a low sodium diet (target 50 mmol Na+/day) and a regular sodium diet (target 200 mmol Na+/day), with a background of ACE inhibition (lisinopril 40 mg/day) during the entire study. The drug interventions were double blind; the dietary interventions were open label. Main outcome measures The primary outcome measure was proteinuria; the secondary outcome measure was blood pressure. Results Mean urinary sodium excretion, a measure of dietary sodium intake, was 106 (SE 5) mmol Na+/day during a low sodium diet and 184 (6) mmol Na+/day during a regular sodium diet (P<0.001). Geometric mean residual proteinuria was 1.68 (95% confidence interval 1.31 to 2.14) g/day during ACE inhibition plus a regular sodium diet. Addition of angiotensin receptor blockade to ACE inhibition reduced proteinuria to 1.44 (1.07 to 1.93) g/day (P=0.003), addition of a low sodium diet reduced it to 0.85 (0.66 to 1.10) g/day (P<0.001), and addition of angiotensin receptor blockade plus a low sodium diet reduced it to 0.67 (0.50 to 0.91) g/day (P<0.001). The reduction of proteinuria by the addition of a low sodium diet to ACE inhibition (51%, 95% confidence interval 43% to 58%) was significantly larger (P<0.001) than the reduction of proteinuria by the addition of angiotensin receptor blockade to ACE inhibition (21%, (8% to 32%) and was comparable (P=0.009, not significant after Bonferroni correction) to the reduction of proteinuria by the addition of both angiotensin receptor blockade and a low sodium diet to ACE inhibition (62%, 53% to 70%). Mean systolic blood pressure was 134 (3) mm Hg during ACE inhibition plus a regular sodium diet. Mean systolic blood pressure was not significantly altered by the addition of angiotensin receptor blockade (131 (3) mm Hg; P=0.12) but was reduced by the addition of a low sodium diet (123 (2) mm Hg; P<0.001) and angiotensin receptor blockade plus a low sodium diet (121 (3) mm Hg; P<0.001) to ACE inhibition. The reduction of systolic blood pressure by the addition of a low sodium diet (7% (SE 1%)) was significantly larger (P=0.003) than the reduction of systolic blood pressure by the addition of angiotensin receptor blockade (2% (1)) and was similar (P=0.14) to the reduction of systolic blood pressure by the addition of both angiotensin receptor blockade and low sodium diet (9% (1)), to ACE inhibition. Conclusions Dietary sodium restriction to a level recommended in guidelines was more effective than dual blockade for reduction of proteinuria and blood pressure in non-diabetic nephropathy. The findings support the combined endeavours of patients and health professionals to reduce sodium intake. Trial registration Netherlands Trial Register NTR675.
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影响因子：
6.1
作者：
Esnault, Vincent L. M.;Ekhlas, Amr;Moranne, Olivier
通讯作者：
Moranne, Olivier
影响因子：
13.2
作者：
Catapano, Fausta;Chiodini, Paolo;Conte, Giuseppe
通讯作者：
Conte, Giuseppe
影响因子：
13.6
作者：
Esnault, VLM;Ekhlas, A;Nguyen, JM
通讯作者：
Nguyen, JM
影响因子：
6.1
作者：
Buter, H;Hemmelder, MH;de Zeeuw, D
通讯作者：
de Zeeuw, D
影响因子：
19.6
作者：
Laverman, GD;Navis, G;dE Zeeuw, D
通讯作者：
dE Zeeuw, D