Kuriyama S, Hopp L, Yoshida H, Hikita M, Tomonari H, Hashimoto T, Sakai O
Division of Nephrology, Saiseikai Central Hospital, Tokyo, Japan.
Am J Hypertens. 1996 May;9(5):426-31. doi: 10.1016/0895-7061(95)00444-0.
Evidence for the involvement of endothelial cells in the pathogenesis or erythropoietin-induced hypertension, and for endothelial cell damage in patients with chronic renal failure, has emerged and appears to be of major concern. We, therefore, investigated the effect of recombinant human erythropoietin (rHuEPO) therapy on endothelium-derived hormones in predialysis patients with progressive renal anemia. At the entry to the trial, the serum thrombomodulin concentration (Tm) and plasma endothelin-1 concentration (ET-1) in the predialysis patients were significantly higher than those in age- and sex-matched normal subjects. Following a 16 week period of treatment with 6000IU rHuEPO given intravenously once a week, patients' hematocrit increased from 27.1 +/- 2.6% to 34.6 +/- 3.2% (n = 16, P < .001). A positive correlation was found between Tm and serum creatinine concentration (Cr) (r = 0.61, P < .05 (n = 16), but no correlation was found between ET-1 and Cr. Tm and Tm/Cr significantly decreased from 7.9 +/- 2.8 ng/mL to 6.6 +/- 2.4 ng/mL (P < .01, n = 16), and from 2.1 +/- 0.7 (x10(-10) to 1.6 +/- 0.7 (x10(-10), P < .01, n = 16), respectively. However, there was no change in ET-1 as a result of the rHuEPO therapy. Creatinine clearance (Ccr), Cr, total amount of daily Tm excretion, Tm clearance/Ccr, daily urinary protein and albumin excretion, and blood pressure also remained unchanged throughout the trail. The present study indicates that correcting anemia by rHuEPO therapy reduces an abnormally elevated Tm in predialysis patients while blood pressure and renal function remain unchanged, suggesting that rHuEPO has a beneficial effect on endothelial cell dysfunction in chronic renal failure patients. This effect may be mediated via an improved oxygen supply to the endothelial cells due to the amelioration of anemia by rHuEPO.
内皮细胞参与促红细胞生成素诱导的高血压发病机制以及慢性肾衰竭患者存在内皮细胞损伤的证据已经出现，且似乎备受关注。因此，我们研究了重组人促红细胞生成素（rHuEPO）治疗对进行性肾性贫血的透析前患者内皮衍生激素的影响。在试验开始时，透析前患者的血清血栓调节蛋白浓度（Tm）和血浆内皮素-1浓度（ET-1）显著高于年龄和性别匹配的正常受试者。在用6000IU rHuEPO每周静脉注射一次进行16周治疗后，患者的血细胞比容从27.1±2.6%增至34.6±3.2%（n = 16，P <.001）。发现Tm与血清肌酐浓度（Cr）之间存在正相关（r = 0.61，P <.05，n = 16），但ET-1与Cr之间未发现相关性。Tm和Tm/Cr分别从7.9±2.8 ng/mL显著降至6.6±2.4 ng/mL（P <.01，n = 16），以及从2.1±0.7（×10⁻¹⁰）降至1.6±0.7（×10⁻¹⁰），P <.01，n = 16）。然而，rHuEPO治疗后ET-1没有变化。肌酐清除率（Ccr）、Cr、每日Tm排泄总量、Tm清除率/Ccr、每日尿蛋白和白蛋白排泄量以及血压在整个试验过程中也保持不变。本研究表明，通过rHuEPO治疗纠正贫血可降低透析前患者异常升高的Tm，而血压和肾功能保持不变，提示rHuEPO对慢性肾衰竭患者的内皮细胞功能障碍具有有益作用。这种作用可能是由于rHuEPO改善贫血从而改善了内皮细胞的氧供应介导的。
