Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Transplantation. 2018 Jan;102(1):79-87. doi: 10.1097/TP.0000000000001895.
Kidneys derived from brain-dead (BD) donors have lower graft survival rates compared with kidneys from living donors. Complement activation plays an important role in brain death. The aim of our study was therefore to investigate the effect of C1-inhibitor (C1-INH) on BD-induced renal injury.
Brain death was induced in rats by inflating a subdurally placed balloon catheter. Thirty minutes after BD, rats were treated with saline, low-dose or high-dose C1-INH. Sham-operated rats served as controls. After 4 hours of brain death, renal function, injury, inflammation, and complement activation were assessed.
High-dose C1-INH treatment of BD donors resulted in significantly lower renal gene expression and serum levels of IL-6. Treatment with C1-INH also improved renal function and reduced renal injury, reflected by the significantly lower kidney injury marker 1 gene expression and lower serum levels of lactate dehydrogenase and creatinine. Furthermore, C1-INH effectively reduced complement activation by brain death and significantly increased functional levels. However, C1-INH treatment did not prevent renal cellular influx.
Targeting complement activation after the induction of brain death reduced renal inflammation and improved renal function before transplantation. Therefore, strategies targeting complement activation in human BD donors might clinically improve donor organ viability and renal allograft survival.
与来自活体供体的肾脏相比，来源于脑死亡（BD）供体的肾脏移植物的存活率较低。补体激活在脑死亡中起重要作用。因此，我们的研究目的是研究 C1 抑制剂（C1-INH）对 BD 诱导的肾损伤的影响。
通过在硬脑膜下放置气囊导管来诱导大鼠脑死亡。BD 后 30 分钟，大鼠用生理盐水、低剂量或高剂量 C1-INH 治疗。假手术大鼠作为对照。脑死亡 4 小时后，评估肾功能、损伤、炎症和补体激活。
BD 供体的高剂量 C1-INH 治疗导致肾基因表达和血清 IL-6 水平显著降低。C1-INH 治疗还改善了肾功能并减轻了肾损伤，这反映在肾损伤标志物 1 基因表达和血清乳酸脱氢酶和肌酐水平降低。此外，C1-INH 有效减少了脑死亡引起的补体激活，并显著增加了功能水平。然而，C1-INH 治疗并不能防止肾细胞浸润。
在脑死亡诱导后靶向补体激活可减少移植前的肾脏炎症并改善肾功能。因此，针对人类 BD 供体补体激活的策略可能会在临床上提高供体器官的活力和肾移植的存活率。
