Add-on angiotensin II receptor blockade lowers urinary transforming growth factor-beta levels.
Add-on angiotensin II receptor blockade lowers urinary transforming growth factor-beta levels.
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附加血管紧张素 II 受体阻断剂可降低尿转化生长因子-β 水平。
DOI：
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发表时间：
2002
影响因子：
13.2
通讯作者：
K. Sharma
中科院分区：
文献类型：
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作者：
R. Agarwal;S. Siva;S. Dunn;K. Sharma
尽管在蛋白尿肾病患者中使用血管紧张素转换酶（ACE）抑制剂具有肾保护作用，但肾功能衰竭的进展可能是由通过血管紧张素II亚型1（AT 1）受体持续产生转化生长因子-β 1（TGF-β 1）引起的。我们检验了一个假设，即在长期最大ACE抑制剂治疗的基础上加用AT 1受体阻滞剂治疗会导致此类患者尿TGF-β 1水平降低。16例患者完成了一项两阶段、交叉、随机、对照试验，其详细信息已在先前报告。所有患者均给予赖诺普利40 mg/d，氯沙坦50 mg/d或安慰剂。使用24小时动态血压监测仪测量血压（BP）。分析过夜尿液标本的尿TGF-β 1、蛋白质和肌酐浓度。研究人群的平均年龄为53 ± 9（SD）岁;体重指数为38 ± 5.7 kg/m2;坐位血压为156 ± 18/88 ± 12 mm Hg;尿蛋白排泄量为3.6 ± 0.71 g/g肌酐。12名患者患有糖尿病肾病，其余患者患有慢性肾小球肾炎。基线时，研究人群的尿TGF-β 1水平显著高于健康对照组（13.2 +/- 1.2 vs 1.7 +/- 1.1 ng/g肌酐; P < 0.001）。基线尿蛋白排泄量与尿TGF-β 1水平（r2 = 0.53; P = 0.001）以及收缩压与尿TGF-β 1水平（r2 = 0.57; P < 0.001）之间存在强相关性。在添加氯沙坦治疗4周后，尿TGF-β 1水平下降38%（95%置信区间[CI]，16%-55%）（13.3 [95% CI，11.4 - 15.5]-8.2 pg/mg肌酐[95% CI，6.2 - 10.7]）。尿TGF-β 1水平的降低与平均尿蛋白排泄量或血压的变化无关。因此，尽管有最大程度的ACE抑制，伴有肾功能衰竭的蛋白尿患者尿TGF-β 1水平升高，并在氯沙坦添加治疗1个月后得到改善。我们推测，氯沙坦和ACE抑制剂的双重阻断可能通过减少肾脏TGF-β 1的产生提供额外的肾脏保护。
Progression of renal failure, despite renoprotection with angiotensin-converting enzyme (ACE) inhibitors in patients with proteinuric nephropathies, may be caused by persistent renal production of transforming growth factor-beta1 (TGF-beta1) through the angiotensin II subtype 1 (AT1) receptors. We tested the hypothesis that AT1-receptor blocker therapy added to a background of chronic maximal ACE inhibitor therapy will result in a reduction in urinary TGF-beta1 levels in such patients. Sixteen patients completed a two-period, crossover, randomized, controlled trial, details of which have been previously reported. All patients were administered lisinopril, 40 mg/d, with either losartan, 50 mg/d, or placebo. Blood pressure (BP) was measured using a 24-hour ambulatory BP monitor. Overnight specimens of urine were analyzed for urine TGF-beta1, protein, and creatinine concentrations. Mean age of the study population was 53 +/- 9 (SD) years; body mass index, 38 +/- 5.7 kg/m2; seated BP, 156 +/- 18/88 +/- 12 mm Hg; and urine protein excretion, 3.6 +/- 0.71 g/g of creatinine. Twelve patients had diabetic nephropathy, and the remainder had chronic glomerulonephritis. At baseline, urinary TGF-beta1 levels were significantly increased in the study population compared with healthy controls (13.2 +/- 1.2 versus 1.7 +/- 1.1 ng/g creatinine; P < 0.001). There was a strong correlation between baseline urine protein excretion and urinary TGF-beta1 level (r2 = 0.53; P = 0.001), as well as systolic BP and urinary TGF-beta1 level (r2 = 0.57; P < 0.001). After 4 weeks of add-on losartan therapy, there was a 38% (95% confidence interval [CI], 16% to 55%) decline in urinary TGF-beta1 levels (13.3 [95% CI, 11.4 to 15.5] to 8.2 pg/mg creatinine [95% CI, 6.2 to 10.7]). The reduction in urinary TGF-beta1 levels occurred independent of changes in mean urinary protein excretion or BP. Thus, proteinuric patients with renal failure, despite maximal ACE inhibition, had increased urinary levels of TGF-beta1 that improved over 1 month of add-on therapy with losartan. We speculate that dual blockade with losartan and an ACE inhibitor may provide additional renoprotection by decreasing renal production of TGF-beta1.
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DOI：
10.1073/pnas.120055097
发表时间：
2000-07-05
影响因子：
11.1
作者：
Ziyadeh, FN;Hoffman, BB;Sharma, K
通讯作者：
Sharma, K
影响因子：
15.9
作者：
KAGAMI, S;BORDER, WA;NOBLE, NA
通讯作者：
NOBLE, NA
影响因子：
158.5
作者：
Klag, MJ;Whelton, PK;Stamler, J
通讯作者：
Stamler, J
影响因子：
19.6
作者：
Peters, H;Border, WA;Noble, NA
通讯作者：
Noble, NA
影响因子：
15.9
作者：
WOLF, G;MUELLER, E;ZIYADEH, FN
通讯作者：
ZIYADEH, FN