Huisman Gerrie Joelle Julia, Berger Stefan P, Thyrrestrup Peter S, Hausken John, Veelo Denise P, Guirado Luis, Pol Robert, Jensen Luana L, Tønnessen Tor Inge, Bemelman Frederike J, Facundo Carme, Tamasi Katalin, Lunter Gerton, Jespersen Bente, Leuvenink Henri G D, Struys Michel M R F, Nieuwenhuijs-Moeke Gertrude J
Department of Anaesthesiology, University Medical Centre Groningen (UMCG), University of Groningen, Groningen, Netherlands.
Department of Nephrology, University Medical Centre Groningen (UMCG), University of Groningen, Groningen, Netherlands.
BMJ Open. 2025 Sep 2;15(9):e098965. doi: 10.1136/bmjopen-2025-098965.
Ischaemia reperfusion injury (IRI) is inevitable in kidney transplantation and negatively affects patient and graft outcomes. Anaesthetic conditioning (AC) refers to the use of anaesthetic agents to mitigate IRI. AC is particularly associated with volatile anaesthetic (VA) agents and to a lesser extent to intravenous agents like propofol. VA like sevoflurane interferes with many of the processes underlying IRI and exerts renal protective properties in various models of injury and inflammation. We hypothesise that a sevoflurane-based anaesthesia is able to induce AC and thereby reduce post-transplant renal injury, reflected in improved graft and patient outcome, compared with a propofol-based anaesthesia in transplant recipients of a deceased donor kidney.
Investigator-initiated, multicentre, randomised, controlled and prospective clinical trial with two parallel groups. The study will include 488 kidney transplant recipients from donation after brain death (DBD) or donation after circulatory death (DCD) donors. Participants are randomised in a 1:1 design to a sevoflurane (intervention) or propofol (control) group. The primary endpoint is the incidence of delayed graft function in recipients of DCD and DBD donor kidneys and/or 1-year biopsy-proven and treated acute rejection. Secondary endpoints include functional delayed graft function defined as failure of serum creatinine levels to decrease by at least 10% per day for three consecutive days; primary non-function is defined as a permanent lack of function of the allograft; length of hospital stay and postoperative complications of all kinds, estimated glomerular filtration rate at 1 week and 3 and 12 months calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula; readmissions at 3 and 12 months, graft survival and all-cause mortality at 12 months.
The study is approved by the local ethical committees and national data security agencies. Results are expected to be published in 2025.
NCT02727296.
缺血再灌注损伤（IRI）在肾移植中不可避免，会对患者和移植物的预后产生负面影响。麻醉预处理（AC）是指使用麻醉药物减轻IRI。AC尤其与挥发性麻醉（VA）药物相关，在较小程度上与丙泊酚等静脉麻醉药物有关。像七氟醚这样的VA会干扰IRI的许多潜在过程，并在各种损伤和炎症模型中发挥肾脏保护作用。我们假设，与已故供体肾移植受者使用丙泊酚麻醉相比，基于七氟醚的麻醉能够诱导AC，从而减少移植后肾损伤，这体现在移植物和患者预后的改善上。
由研究者发起的多中心、随机、对照、前瞻性临床试验，分为两个平行组。该研究将纳入488名来自脑死亡后捐赠（DBD）或循环死亡后捐赠（DCD）供体的肾移植受者。参与者按1:1设计随机分为七氟醚（干预）组或丙泊酚（对照）组。主要终点是DCD和DBD供体肾受者延迟移植肾功能的发生率和/或1年活检证实并治疗的急性排斥反应。次要终点包括功能性延迟移植肾功能，定义为血清肌酐水平连续三天每天至少下降10%失败；原发性无功能定义为同种异体移植物永久性缺乏功能；住院时间和各类术后并发症，使用慢性肾脏病流行病学协作组（CKD-EPI）公式计算1周、3个月和12个月时的估计肾小球滤过率；3个月和12个月时的再次入院情况，12个月时的移植物存活率和全因死亡率。
该研究已获得当地伦理委员会和国家数据安全机构的批准。预计结果将于2025年发表。
NCT02727296
