Ischemia and reperfusion injury in renal transplantation: hemodynamic and immunological paradigms

Ischemia and reperfusion injury is an inevitable event in renal transplantation. The most important consequences are delayed graft function, longer length of stay, higher hospital costs, high risk of acute rejection, and negative impact of long-term follow-up. Currently, many factors are involved in their pathophysiology and could be classified into two different paradigms for education purposes: hemodynamic and immune. The hemodynamic paradigm is described as the reduction of oxygen delivery due to blood flow interruption, involving many hormone systems, and oxygen-free radicals produced after reperfusion. The immune paradigm has been recently described and involves immune system cells, especially T cells, with a central role in this injury. According to these concepts, new strategies to prevent ischemia and reperfusion injury have been studied, particularly the more physiological forms of storing the kidney, such as the pump machine and the use of antilymphocyte antibody therapy before reperfusion. Pump machine perfusion reduces delayed graft function prevalence and length of stay at hospital, and increases long-term graft survival. The use of antilymphocyte antibody therapy before reperfusion, such as Thymoglobulin™, can reduce the prevalence of delayed graft function and chronic graft dysfunction.

缺血再灌注损伤是肾移植中无法避免的事件。其最主要的不良结局包括移植肾功能延迟恢复（delayed graft function）、住院时间延长、住院费用升高、急性排斥反应风险升高，以及对长期随访结局产生负面影响。目前，该损伤的病理生理学机制涉及多种因素，为便于教学可将其归纳为两类不同范式：血流动力学范式与免疫范式。血流动力学范式指因血流中断导致氧供减少，涉及多种激素系统，以及再灌注后产生的氧自由基。免疫范式则是近年被提出的分类维度，其涉及免疫系统细胞，尤其是T细胞，在该损伤中发挥核心作用。基于上述理论，学界已开展多种预防缺血再灌注损伤的新策略研究，其中尤以更贴合生理状态的肾脏保存方式为重点，如机械灌注泵（pump machine）技术，以及再灌注前应用抗淋巴细胞抗体治疗。机械灌注泵灌注可降低移植肾功能延迟恢复的发生率，缩短住院时长，并提高移植物长期存活率。再灌注前使用抗淋巴细胞抗体治疗（如Thymoglobulin™），可降低移植肾功能延迟恢复与慢性移植物功能障碍的发生率。