Abe M, Okada K, Maruyama T, Matsumoto S, Matsumoto K
Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan.
Int J Clin Pharmacol Ther. 2010 Mar;48(3):206-13. doi: 10.5414/cpp48206.
We evaluated the changes in the blood pressure and urinary protein excretion in poorly controlled hypertensive and proteinuric patients with mild to moderate chronic kidney disease (CKD) after switching from the high-dose angiotensin receptor blockers (ARBs) to a combination of normal-dose telmisartan (40 mg) and low-dose hydrochlorothiazide (HCTZ; 12.5 mg).
60 adults with Stages 2 - 3 CKD who had been receiving high-dose ARBs and had not achieved their target blood pressure of 130/80 mmHg were switched to a combination of telmisartan (40 mg) and HCTZ (12.5 mg) once daily for a 12-week study period. We measured the blood pressure, pulse rate, urinary protein excretion, and total monthly drug costs before and after the switch.
The mean systolic blood pressure dropped from 153 to 133 mm Hg and the mean diastolic blood pressure, from 89 to 78 mmHg (p < 0.0001, for both). Further, the mean blood pressure decreased (p < 0.0001), without any significant change in the pulse rate. Urinary protein excretion adjusted for urinary creatinine was reduced from 3,749 to 2,474 mg/g creatinine (p < 0.0001). No significant change was detected in the estimated glomerular filtration rate and serum creatinine level. With the switching from high-dose ARBs to the combination of normal-dose telmisartan and low-dose HCTZ treatment, the blood pressure decreased in all the subjects, and 36% of all the subjects achieved optimal blood pressure levels. No adverse metabolic effects were noted even among the diabetic patients. The monthly drug costs were significantly reduced after the switch (13,614 +/- 6,108 vs. 9,936 +/- 5,571 yen/month, p < 0.0001).
We concluded that the telmisartan and HCTZ combination may be more efficacious than monotherapy of the high-dose ARBs in reducing blood pressure and urinary protein excretion in hypertensive patients with CKD. Further investigation would be required to assess whether the combination of high-dose ARBs and low-dose HCTZ has a greater antiproteinuric effect than the combination of normal-dose telmisartan (40 mg) and low-dose HCTZ (12.5 mg).
我们评估了血压控制不佳且伴有蛋白尿的轻至中度慢性肾脏病（CKD）患者，从高剂量血管紧张素受体阻滞剂（ARB）转换为常规剂量替米沙坦（40毫克）与低剂量氢氯噻嗪（HCTZ；12.5毫克）联合用药后血压和尿蛋白排泄的变化。
60名2 - 3期CKD成人患者，此前一直在接受高剂量ARB治疗，但未达到130/80 mmHg的目标血压，在为期12周的研究期间，改为每日一次服用替米沙坦（40毫克）和HCTZ（12.5毫克）的联合用药。我们在换药前后测量了血压、脉搏率、尿蛋白排泄量和每月总药费。
平均收缩压从153毫米汞柱降至133毫米汞柱，平均舒张压从89毫米汞柱降至78毫米汞柱（两者均为p < 0.0001）。此外，平均血压下降（p < 0.0001），脉搏率无显著变化。经尿肌酐校正后的尿蛋白排泄量从3749毫克/克肌酐降至2474毫克/克肌酐（p < 0.0001）。估计肾小球滤过率和血清肌酐水平未发现显著变化。从高剂量ARB转换为常规剂量替米沙坦与低剂量HCTZ联合治疗后，所有受试者的血压均下降，36%的受试者达到了最佳血压水平。即使在糖尿病患者中也未观察到不良代谢影响。换药后每月药费显著降低（13614 ± 6108日元/月对9936 ± 5571日元/月，p < 0.0001）。
我们得出结论，在降低CKD高血压患者的血压和尿蛋白排泄方面，替米沙坦与HCTZ联合用药可能比高剂量ARB单药治疗更有效。需要进一步研究来评估高剂量ARB与低剂量HCTZ联合用药是否比常规剂量替米沙坦（40毫克）与低剂量HCTZ（12.5毫克）联合用药具有更大的抗蛋白尿作用。
