Kaths J Moritz, Echeverri Juan, Goldaracena Nicolas, Louis Kristine S, Yip Paul, John Rohan, Mucsi Istvan, Ghanekar Anand, Bagli Darius, Selzner Markus, Robinson Lisa A
Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital; Division of Nephrology, The Hospital for Sick Children;
Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital; Programa de Doctorat en Medicina, La Universitat Autónoma de Barcelona.
J Vis Exp. 2016 Feb 21(108):53765. doi: 10.3791/53765.
Kidney transplantation is the treatment of choice for patients suffering from end-stage renal disease. It offers better life expectancy and higher quality of life when compared to dialysis. Although the last few decades have seen major improvements in patient outcomes following kidney transplantation, the increasing shortage of available organs represents a severe problem worldwide. To expand the donor pool, marginal kidney grafts recovered from extended criteria donors (ECD) or donated after circulatory death (DCD) are now accepted for transplantation. To further improve the postoperative outcome of these marginal grafts, research must focus on new therapeutic approaches such as alternative preservation techniques, immunomodulation, gene transfer, and stem cell administration. Experimental studies in animal models are the final step before newly developed techniques can be translated into clinical practice. Porcine kidney transplantation is an excellent model of human transplantation and allows investigation of novel approaches. The major advantage of the porcine model is its anatomical and physiological similarity to the human body, which facilitates the rapid translation of new findings to clinical trials. This article offers a surgical step-by-step protocol for an autotransplantation model and highlights key factors to ensure experimental success. Adequate pre- and postoperative housing, attentive anesthesia, and consistent surgical techniques result in favorable postoperative outcomes. Resection of the contralateral native kidney provides the opportunity to assess post-transplant graft function. The placement of venous and urinary catheters and the use of metabolic cages allow further detailed evaluation. For long-term follow-up studies and investigation of alternative graft preservation techniques, autotransplantation models are superior to allotransplantation models, as they avoid the confounding bias posed by rejection and immunosuppressive medication.
肾移植是终末期肾病患者的首选治疗方法。与透析相比,它能提供更长的预期寿命和更高的生活质量。尽管在过去几十年里,肾移植术后患者的预后有了重大改善,但可用器官日益短缺仍是全球范围内的一个严重问题。为了扩大供体库,现在已接受从扩大标准供体(ECD)获取的边缘性肾移植物或循环死亡后捐赠(DCD)的肾移植物进行移植。为了进一步改善这些边缘性移植物的术后结果,研究必须聚焦于新的治疗方法,如替代保存技术、免疫调节、基因转移和干细胞给药。动物模型的实验研究是将新开发的技术转化为临床实践的最后一步。猪肾移植是人类移植的一个优秀模型,可用于研究新方法。猪模型的主要优势在于其与人体在解剖学和生理学上的相似性,这便于将新发现快速转化为临床试验。本文提供了一个自体移植模型的手术分步方案,并强调了确保实验成功的关键因素。术前和术后提供适当的饲养环境、细心的麻醉和一致的手术技术可带来良好的术后结果。切除对侧的天然肾脏为评估移植后移植物功能提供了机会。放置静脉和导尿管以及使用代谢笼可进行更详细的评估。对于长期随访研究和替代移植物保存技术的研究,自体移植模型优于同种异体移植模型,因为它们避免了排斥反应和免疫抑制药物带来的混杂偏倚。