Mundt Heiko M, Yard Benito A, Krämer Bernhard K, Benck Urs, Schnülle Peter
5th Department of Medicine (Nephrology/Endocrinology/Rheumatology), Medical Faculty Mannheim of the University of Heidelberg, University Hospital Mannheim, Mannheim, Germany.
Transpl Int. 2016 Sep;29(9):974-84. doi: 10.1111/tri.12712. Epub 2015 Dec 9.
Kidney transplantation is a major medical improvement for patients with end-stage renal disease, but organ shortage limits its widespread use. As a consequence, the proportion of grafts procured from extended criteria donors (ECD) has increased considerably, but this comes along with increased rates of delayed graft function (DGF) and a higher incidence of immune-mediated rejection that limits organ and patient survival. Furthermore, most grafts are derived from brain dead organ donors, but the unphysiological state of brain death is associated with significant metabolic, hemodynamic, and pro-inflammatory changes, which further compromise patient and graft survival. Thus, donor interventions to preserve graft quality are fundamental to improve long-term transplantation outcome, but interventions must not harm other potentially transplantable grafts. Several donor pretreatment strategies have provided encouraging results in animal models, but evidence from human studies is sparse, as most clinical evidence is derived from single-center or nonrandomized trials. Furthermore, ethical matters have to be considered especially concerning consent from donors, donor families, and transplant recipients to research in the field of donor treatment. This review provides an overview of clinically proven and promising preclinical strategies of donor treatment to optimize long-term results after kidney transplantation.
肾移植是终末期肾病患者医学上的一项重大进步,但器官短缺限制了其广泛应用。因此,从扩大标准供体(ECD)获取的移植物比例大幅增加,但这伴随着移植肾功能延迟恢复(DGF)发生率的上升以及免疫介导排斥反应的更高发生率,而这限制了器官和患者的存活。此外,大多数移植物来自脑死亡器官供体,但脑死亡的非生理状态与显著的代谢、血流动力学和促炎变化相关,这进一步损害了患者和移植物的存活。因此,供体干预以保存移植物质量对于改善长期移植结果至关重要,但干预不得损害其他潜在可移植的移植物。几种供体预处理策略在动物模型中取得了令人鼓舞的结果,但人体研究的证据稀少,因为大多数临床证据来自单中心或非随机试验。此外,尤其在涉及供体、供体家属和移植受者对供体治疗领域研究的同意方面,必须考虑伦理问题。本综述概述了经临床验证且有前景的供体治疗临床前策略,以优化肾移植后的长期结果。