Department of Pediatrics, Albert Szent-Györgyi Clinical Center, University of Szeged, Korányi fasor 14-15, Szeged, 6720, Hungary.
Clin Exp Nephrol. 2013 Aug;17(4):569-74. doi: 10.1007/s10157-012-0749-5. Epub 2012 Dec 6.
The development of erythropoiesis-stimulating agents (ESAs) with extended serum half-lives has allowed marked prolongation of the administration intervals. The level of oxidative stress is increased in chronic kidney disease, and is reportedly decreased after long-term ESA treatment. However, the effect of different dosing regimens of ESAs on oxidative stress has not been elucidated.
Five-sixths nephrectomized (NX) rats received either 0.4 μg/kg darbepoetin alfa (DA) weekly or 0.8 μg/kg DA fortnightly between weeks 4 and 10. NX animals receiving saline and a sham-operated (SHAM) group served as controls. The levels of oxidized and reduced glutathione (GSSG, GSH) were followed from blood samples drawn fortnightly.
During the follow-up, the ratios GSSG/GSH showed similar trends in both DA groups, levels being significantly lower than those in the SHAM group at weeks 8 and 10. GSSG levels were lower than the baseline throughout the study in all groups except for NX controls. The GSH levels were increased in all three NX groups (weeks 6-10) compared with both the baseline and the SHAM group
Our results suggest that the extent of oxidative stress is similar in response to different dosing regimens of DA in 5/6 NX rats when comparable hemoglobin levels are maintained. These findings remain to be confirmed in chronic kidney disease patients.
红细胞生成刺激剂（ESAs）的血清半衰期延长，使给药间隔明显延长。慢性肾脏病患者的氧化应激水平升高，据报道，长期 ESA 治疗后会降低。然而，不同 ESA 给药方案对氧化应激的影响尚未阐明。
5/6 肾切除术（NX）大鼠在第 4 至 10 周期间每周接受 0.4μg/kg 达贝泊汀α（DA）或每两周接受 0.8μg/kg DA。接受生理盐水的 NX 动物和假手术（SHAM）组作为对照。每隔两周从血液样本中检测氧化型和还原型谷胱甘肽（GSSG、GSH）的水平。
在随访期间，两组 DA 的 GSSG/GSH 比值呈相似趋势，第 8 和 10 周时均显著低于 SHAM 组。除 NX 对照组外，所有组的 GSSG 水平在整个研究过程中均低于基线。与基线和 SHAM 组相比，所有三组 NX（第 6-10 周）的 GSH 水平均升高。
我们的研究结果表明，在维持相当的血红蛋白水平时，5/6 NX 大鼠对不同 DA 给药方案的氧化应激程度相似。这些发现仍需在慢性肾脏病患者中得到证实。
