Walsh Liron, Dinavahi Rajani
Amgen, Nephrology Therapeutic Area, Thousand Oaks, CA.
One Amgen Center Dr, Bldg 38, Mail Stop 38-3C, Thousand Oaks, CA 91320,
Front Biosci (Elite Ed). 2016 Jan 1;8(1):1-14. doi: 10.2741/746.
While has been considerable progress in the short-term outcomes following renal transplantation over the last several decades, minimal gains have been made with regards to long-term graft function and patient survival (1). The lack of long-term gains has been attributed to factors such as antibody mediated rejection (AMR), chronic allograft nephropathy (CAN), and toxicity to the allograft secondary to immunosuppression. Ischemia reperfusion injury (IRI) is also thought to contribute to poor long-term graft function, and its impact on patient and graft outcomes will likely expand with the increasing use of marginal kidneys secondary to organ shortages. While patient survival remains far below that of the general population, the causes of death have evolved in recent years with decreases in the rate of death from cardiovascular disease and infection, and increases secondary to malignancy (2), which are largely attributable to the potency of modern immunosuppression. As such, the development of novel therapies which can prevent delayed graft function (DGF), minimize AMR, while simultaneously reducing toxicity is vital to the improvement of long-term graft and patient outcomes.
在过去几十年里，肾移植术后的短期疗效已有显著进展，但在长期移植物功能和患者生存率方面进展甚微（1）。长期疗效欠佳归因于多种因素，如抗体介导的排斥反应（AMR）、慢性移植肾肾病（CAN）以及免疫抑制导致的移植物毒性。缺血再灌注损伤（IRI）也被认为会导致长期移植物功能不佳，随着器官短缺导致边缘供肾使用的增加，其对患者和移植物结局的影响可能会扩大。虽然患者生存率仍远低于普通人群，但近年来死亡原因有所演变，心血管疾病和感染导致的死亡率下降，而恶性肿瘤导致的死亡率上升（2），这在很大程度上归因于现代免疫抑制的效力。因此，开发能够预防移植肾功能延迟恢复（DGF）、最大限度减少AMR并同时降低毒性的新型疗法，对于改善长期移植物和患者结局至关重要。
