Tamura Yoshifuru, Kosuga Masahiro, Yamashita Masahiro, Tomioka Satoru, Sasaki Michiko, Hikita Tomoyuki, Nakajima Hideaki, Kojima Kenichiro, Uchida Shunya
Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8605, Japan.
Clin Exp Nephrol. 2008 Aug;12(4):256-263. doi: 10.1007/s10157-008-0040-y. Epub 2008 Mar 5.
To investigate the renoprotective effects and safety of angiotensin II receptor blocker (ARB) for patients with stage 4-5 chronic kidney disease.
An ARB, candesartan cilexetil, was administered to 13 patients (ARB group, n = 7; control group, n = 6) with a serum creatinine level of 2.52-5.95 mg/dl whose blood pressure had been maintained below 140/90 mmHg by the use of drugs other than ARBs. Routine measurements were conducted for 48 weeks, and renal survival analysis was observed for up to 3 years with the endpoints being doubling of the serum creatinine level, entry to hemodialysis, or death. The results were compared with those of the control group that was not treated with ARB.
No significant changes were observed in the blood pressure in either group. Proteinuria significantly decreased from 0.95 +/- 0.51 to 0.39 +/- 0.12 g/day (paired t test, P = 0.033) in the ARB group, but did not change in the control group. Creatinine clearance in the control group decreased significantly from 16.2 +/- 5.7 to 10.4 +/- 4.8 ml/min per 1.73 m2 (paired t test, P = 0.011), but did not change in the other group. Thus, the slopes of the reciprocal serum creatinine values became less steep in the ARB group as compared with the control (-0.002 +/- 0.015 vs. -0.025 +/- 0.015 dl/mg per month; unpaired t test, P = 0.019). Kaplan-Meier analysis revealed that ARB exhibited more favorable renal outcome at 3 years (log-rank, P = 0.025). No serious adverse events were noted in the study.
These results show that ARB reduces proteinuria and protects renal function even in the advanced renal failure.
探讨血管紧张素II受体阻滞剂（ARB）对4-5期慢性肾脏病患者的肾脏保护作用及安全性。
对13例血清肌酐水平为2.52-5.95mg/dl的患者（ARB组，n = 7；对照组，n = 6）给予ARB类药物坎地沙坦酯，这些患者的血压通过使用ARB以外的药物维持在140/90mmHg以下。进行了48周的常规测量，并观察了长达3年的肾脏生存分析，终点为血清肌酐水平翻倍、开始血液透析或死亡。将结果与未接受ARB治疗的对照组进行比较。
两组血压均无显著变化。ARB组蛋白尿从0.95±0.51g/天显著降至0.39±0.12g/天（配对t检验，P = 0.033），而对照组未发生变化。对照组的肌酐清除率从每1.73m² 16.2±5.7显著降至10.4±4.8ml/分钟（配对t检验，P = 0.011），而另一组未发生变化。因此，与对照组相比，ARB组血清肌酐倒数的斜率变得不那么陡峭（-0.002±0.015 vs. -0.025±0.015dl/mg每月；非配对t检验，P = 0.019）。Kaplan-Meier分析显示，ARB在3年时表现出更有利的肾脏结局（对数秩检验，P = 0.025）。研究中未观察到严重不良事件。
这些结果表明，即使在晚期肾衰竭中，ARB也能减少蛋白尿并保护肾功能。
