van Rijt Willem G, Secher Niels, Keller Anna K, Møldrup Ulla, Chynau Yahor, Ploeg Rutger J, van Goor Harry, Nørregaard Rikke, Birn Henrik, Frøkiaer Jørgen, Nielsen Søren, Leuvenink Henri G D, Jespersen Bente
Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands; Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands.
Department of Anesthesiology, Aarhus University Hospital, Aarhus, Denmark.
PLoS One. 2014 Apr 11;9(4):e94609. doi: 10.1371/journal.pone.0094609. eCollection 2014.
Delayed graft function and primary non-function are serious complications following transplantation of kidneys derived from deceased brain dead (DBD) donors. α-melanocyte stimulating hormone (α-MSH) is a pleiotropic neuropeptide and its renoprotective effects have been demonstrated in models of acute kidney injury. We hypothesized that α-MSH treatment of the recipient improves early graft function and reduces inflammation following DBD kidney transplantation. Eight Danish landrace pigs served as DBD donors. After four hours of brain death both kidneys were removed and stored for 18 hours at 4°C in Custodiol preservation solution. Sixteen recipients were randomized in a paired design into two treatment groups, transplanted simultaneously. α-MSH or a vehicle was administered at start of surgery, during reperfusion and two hours post-reperfusion. The recipients were observed for ten hours following reperfusion. Blood, urine and kidney tissue samples were collected during and at the end of follow-up. α-MSH treatment reduced urine flow and impaired recovery of glomerular filtration rate (GFR) compared to controls. After each dose of α-MSH, a trend towards reduced mean arterial blood pressure and increased heart rate was observed. α-MSH did not affect expression of inflammatory markers. Surprisingly, α-MSH impaired recovery of renal function in the first ten hours following DBD kidney transplantation possibly due to hemodynamic changes. Thus, in a porcine experimental model α-MSH did not reduce renal inflammation and did not improve short-term graft function following DBD kidney transplantation.
移植来自脑死亡(DBD)供体的肾脏后,移植肾功能延迟和原发性无功能是严重的并发症。α-黑素细胞刺激激素(α-MSH)是一种多效性神经肽,其肾脏保护作用已在急性肾损伤模型中得到证实。我们假设,对受体进行α-MSH治疗可改善DBD肾移植后的早期移植肾功能,并减轻炎症反应。八只丹麦长白猪作为DBD供体。脑死亡四小时后,取出双侧肾脏,并在4°C下于Custodiol保存液中保存18小时。16只受体以配对设计随机分为两个治疗组,同时进行移植。在手术开始时、再灌注期间和再灌注后两小时给予α-MSH或载体。再灌注后对受体观察10小时。在随访期间及随访结束时采集血液、尿液和肾脏组织样本。与对照组相比,α-MSH治疗降低了尿量,并损害了肾小球滤过率(GFR)的恢复。每次给予α-MSH后,观察到平均动脉血压有降低趋势,心率有升高趋势。α-MSH不影响炎症标志物的表达。令人惊讶的是,α-MSH可能由于血流动力学变化而损害了DBD肾移植后最初10小时内的肾功能恢复。因此,在猪实验模型中,α-MSH并未减轻肾脏炎症,也未改善DBD肾移植后的短期移植肾功能。