INSERM U775, Centre Universitaire des Saints Pères, et Université Paris Descartes, Paris, France.
Am J Transplant. 2012 Dec;12(12):3184-90. doi: 10.1111/j.1600-6143.2012.04287.x. Epub 2012 Oct 11.
Adaptive responses to hypoxia, including hypoxia-inducible factor signaling, allow the cell to satisfy its basal metabolic demand and avoid death, but these responses can also be deleterious by promoting inflammation, cell dedifferentiation and fibrogenesis. Therefore, targeting hypoxia constitutes a promising therapeutic avenue. Recombinant human erythropoietin (rhEPO) appeared as a good candidate therapy because its hematopoietic properties could reverse anemia, and its tissue-protective properties could reduce cell death and limit maladaptive cellular responses to hypoxia. Despite experimental evidence on the nephroprotecive properties of rhEPO, recent clinical trials provided evidence that rhEPO was ineffective in preventing delayed graft function after ischemic acute injury but that the normalization of hemoglobin values preserved kidney function deterioration and reduced graft loss. Our aim here is to provide a survey of the rationale for evaluating the administration of rhEPO in the setting of kidney transplantation. We will discuss the intriguing findings that emerged from the clinical trials and the discrepancies between promising experimental results and negative clinical studies, as well as the differences in terms of the benefits and safety profiles of the normalization of hemoglobin values in chronic kidney disease patients and kidney transplant patients.
缺氧的适应性反应，包括缺氧诱导因子信号通路，使细胞能够满足其基本代谢需求并避免死亡，但这些反应也可能通过促进炎症、细胞去分化和纤维化而产生有害影响。因此，针对缺氧成为一种有前途的治疗途径。重组人促红细胞生成素 (rhEPO) 似乎是一种很好的候选治疗药物，因为它的造血特性可以纠正贫血，其组织保护特性可以减少细胞死亡并限制细胞对缺氧的适应性反应。尽管有实验证据表明 rhEPO 具有肾保护作用，但最近的临床试验提供的证据表明，rhEPO 不能预防缺血性急性损伤后延迟移植物功能，但血红蛋白值的正常化可保护肾功能恶化并减少移植物丢失。我们的目的是提供一个评估 rhEPO 在肾移植中的应用的基本原理的综述。我们将讨论临床试验中出现的有趣发现，以及有前途的实验结果与阴性临床研究之间的差异，以及在慢性肾脏病患者和肾移植患者中血红蛋白值正常化的益处和安全性特征方面的差异。
