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Predictive Score Model for Delayed Graft Function Based on hypothermic Machine Perfusion Variables in Kidney Transplantation

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Chinese Medical Journal 2018年第22期131卷 2651-2657页

作者： Chen-Guang Ding Yang Li Xiao-Hui Tian Xiao-Jun Hu Pu-Xun Tian Xiao-Ming Ding He-Li Xiang Jin Zheng Wu-Jun Xue Department of Kidney Transplantation Nephropathy HospitalThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxi 710061China Institute of Organ Transplantation Xi'an Jiaotong UniversityXi'anShaanxi 710061China

Background: hypothermic machine perfusion(HMP) is being used more often in cardiac death kidney transplantation; however, the significance of assessing organ quality and predicting delayed graft function(DGF) by HMP parameters is still controversial. Therefore,we used a readily available HMP variable to design a scoring model that can identify the highest risk of DGF and provide the guidance and advice for organ allocation and DCD kidney assessment.Methods: From September 1, 2012 to August 31, 2016, 366 qualified kidneys were randomly assigned to the development and validation cohorts in a 2:1 distribution. The HMP variables of the development cohort served as candidate univariate predictors for DGF. The independent predictors of DGF were identified by multivariate logistic regression analysis with a P < 0.05. According to the odds ratios(ORs) value, each HMP variable was assigned a weighted integer, and the sum of the integers indicated the total risk score for each kidney. The validation cohort was used to verify the accuracy and reliability of the scoring model.Results: HMP duration(OR = 1.165, 95% confidence interval [CI ]: 1.008–1.360, P = 0.043), resistance(OR = 2.190, 95%CI: 1.032–10.20, P < 0.001), and flow rate(OR = 0.931, 95% CI: 0.894–0.967, P = 0.011) were the independent predictors of identified DGF. The HMP predictive score ranged from 0 to 14, and there was a clear increase in the incidence of DGF, from the low predictive score group to the very high predictive score group. We formed four increasingly serious risk categories(scores 0–3, 4–7, 8–11, and 12–14)according to the frequency associated with the different risk scores of DGF. The HMP predictive score indicates good discriminative power with a c?statistic of 0.706 in the validation cohort, and it had significantly better prediction value for DGF compared to both terminal flow(P = 0.012) and resistance(P = 0.006).Conclusion: The HMP predictive score is a good noninvasive tool for assessing the quality of DCD kidneys, and it is potentially usef

关键词： Delayed Graft Function Donation after Cardiac Death hypothermic Machine Perfusion Kidney Transplantation

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Beneficial Effect of Moderately Increasing hypothermic Machine Perfusion Pressure on Donor after Cardiac Death Renal Transplantation

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Chinese Medical Journal 2018年第22期131卷 2676-2682页

作者： Chen-Guang Ding Pu-Xun Tian Xiao-Ming Ding He-Li Xiang Yang Li Xiao-Hui Tian Feng Han Qian-Hui Tai Qian-Long Liu Jin Zheng Wu-Jun Xue Department of Renal Transplantation Nephropathy HospitalThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxi 710061China Institute of Organ Transplantation Xi'an Jiaotong UniversityXi'anShaanxi 710061China

Background:Vascular resistance and flow rate during hypotherrnic machine perfusion (HMP)of kidneys is correlated with graft function. We aimed to determine the effects of increasing HMP pressure versus maintaining the initial pressure on kidney transplantation outcomes. Methods:We retrospectively reviewed the data of 76 primary transplantation patients who received HMP-preserved kidneys from 48 donors after cardiac death between September 1,2013,and August 31,2015.HMP pressure was increased from 30 to 40mmHg (1mmHg =0.133kPa)in kidneys with poor flow and/or vascular resistance (increased pressure [IP]group;36 patients);otherwise,the initial pressure was maintained (constant pressure group;40 patients).Finally,the clinical characteristics and transplantation outcomes in both groups were assessed. Results:Delayed graft function (DGF)incidence,1-year allograft,patient survival,kidney function recovery time,and serum creatinine level on day 30 were similar in both groups,with improved flow and resistance in the IP group.Among patients with DGF,kidney function recovery time and DGF duration were ameliorated in the IP group.Multivariate logistic regression analysis revealed that donor hypertension (odds ratio [OR]:1.43,95%confidence interval [CI]:1.02-2.06,P =0.035),donor terminal serum creatinine (OR:1.27,95%C7:1.06-1.62,P =0.023),warm ischemic time (OR:3.45,95%CI:1.97-6.37,P =0.002),and terminal resistance (OR:3.12,95%CI:1.76-6.09,P =0.012)were independent predictors of DGF.Cox proportional hazards analysis showed that terminal resistance (hazard ratio:2.06,95%C1:1.32-5.16,P =0.032)significantly affected graft survival. Conclusion:Increased HMP pressure improves graft perfusion but does not affect DGF incidence or 1-year graft survival.

关键词： Delayed Graft Function Donor after Cardiac Death hypothermic Machine Perfusion Kidney Transplantation

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Effect of continuous hypothermic machine perfusion transport system（AirdriveTM） on canine kidney preservation

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Chinese Medical Journal 2014年第6期127卷 1105-1109页

作者： Hu Xiaopeng Xue Wenrui Zhang Qiang Wang Wei Zhang Jiqing Zhang Xiaodong Department of Urology Beijing Chao-Yang Hospital Capital Medical University Beijing 100020 China

Background Organ preservation keeps the quality of the organs under prolonged ischemia. Continuous machineperfusions are gaining an important position in clinical research and practice. The aim of this study was to evaluate theprotective effect of continuous hypothermic machine perfusion transport system （AirdriveTM） on cold ischemic injury ofcanine kidney.

关键词： continuous hypothermic machine perfusion organ preservation organ transplantation canine kidney common cold preservation

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MicroRNA expression in the hippocampal CA1 region under deep hypothermic circulatory arrest

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Neural Regeneration Research 2019年第11期14卷 2003-2010页

作者： Xiao-Hua Wang Dong-Xu Yao Xiu-Shu Luan Yu Wang Hai-Xia Liu Bei Liu Yang Liu Lei Zhao Xun-Ming Ji Tian-Long Wang Department of Anesthesiology Xuanwu HospitalCapital Medical UniversityBeijingChina Institute of Geriatrics BeijingChina National Clinical Research Center for Geriatric Disorders BeijingChina Department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina Cerebrovascular Research Center Xuanwu HospitalCapital Medical UniversityBeijingChina

Using deep hypothermic circulatory arrest, thoracic aorta diseases and complex heart diseases can be subjected to corrective procedures. However, mechanisms underlying brain protection during deep hypothermic circulatory arrest are unclear. After piglet models underwent 60 minutes of deep hypothermic circulatory arrest at 14°C, expression of microRNAs(miRNAs) was analyzed in the hippocampus by microarray. Subsequently, TargetScan 6.2, RNA22 v2.0, miRWalk 2.0, and miRanda were used to predict potential targets, and gene ontology enrichment analysis was carried out to identify functional pathways involved. Quantitative reverse transcription-polymerase chain reaction was conducted to verify miRNA changes. Deep hypothermic circulatory arrest altered the expression of 35 miRNAs. Twenty-two miRNAs were significantly downregulated and thirteen miRNAs were significantly upregulated in the hippocampus after deep hypothermic circulatory arrest. Six out of eight targets among the differentially expressed miRNAs were enriched for neuronal projection(cyclin dependent kinase, CDK16 and SLC1 A2), central nervous system development(FOXO3, TYRO3, and SLC1 A2), ion transmembrane transporter activity(ATP2 B2 and SLC1 A2), and interleukin-6 receptor binding(IL6 R)– these are the key functional pathways involved in cerebral protection during deep hypothermic circulatory arrest. Quantitative reverse transcription-polymerase chain reaction confirmed the results of microarray analysis. Our experimental results illustrate a new role for transcriptional regulation in deep hypothermic circulatory arrest, and provide significant insight for the development of miRNAs to treat brain injuries. All procedures were approved by the Animal Care Committee of Xuanwu Hospital, Capital Medical University, China on March 1, 2017(approval No. XW-INI-AD2017-0112).

关键词： nerve regeneration cerebral protection deep hypothermic circulatory arrest gene ontology enrichment analysis microRNA hippocampus post-transcriptional expression microarray bioinformatics neural regeneration

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Liver graft preservation methods during cold ischemia phase and normothermic machine perfusion

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World Journal of Gastrointestinal Surgery 2019年第3期11卷 126-142页

作者： Konstantin Y Tchilikidi Department of Surgery Altai State Medical University

The growing demand for donor organs requires measures to expand donor pool.Those include extended criteria donors, such as elderly people, steatotic livers,donation after cardiac death, etc. Static cold storage to reduce metabolic requirements developed by Collins in late 1960 s is the mainstay and the golden standard for donated organ protection. hypothermic machine perfusion provides dynamic organ preservation at 4°C with protracted infusion of metabolic substrates to the graft during the ex vivo period. It has been used instead of static cold storage or after it as short perfusion in transplant center. Normothermic machine perfusion(NMP) delivers oxygen, and nutrition at physiological temperature mimicking regular environment in order to support cellular function. This would minimize effects of ischemia/reperfusion injury.Potentially, NMP may help to estimate graft functionality before implantation into a recipient. Clinical studies demonstrated at least its non-inferiority or better outcomes vs static cold storage. Regular grafts donated after brain death could be safely preserved with convenient static cold storage. Except for prolonged ischemia time where hypothermic machine perfusion started in transplant center could be estimated to provide possible positive reconditioning effect. Use of hypothermic machine perfusion in regular donation instead of static cold storage or in extended criteria donors requires further investigation. Multicenter randomized clinical trial supposed to be completed in December 2021. Extended criteria donors need additional measures for graft storage and assessment until its implantation. NMP is actively evaluating promising method for this purpose.Future studies are necessary for precise estimation and confirmation to issue clinical practice recommendations.

关键词： Liver graft preservation Graft preservation solutions Static cold storage hypothermic machine perfusion Normothermic machine perfusion Ischemia-reperfusion injury Marginal grafts Donation after cardiac death Extended criteria donors Transpla complications

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Influence of perfusate on liver viability during hypothermic machine perfusion

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World Journal of Gastroenterology 2015年第29期21卷 8848-8857页

作者： Jun-Jun Jia Jing Zhang Jian-Hui Li Xu-Dong Chen Li Jiang Yan-Fei Zhou Ning He Hai-Yang Xie Lin Zhou Shu-Sen Zheng Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital College of Medicine Zhejiang University Key Laboratory of Combined Multiorgan Transplantation Ministry of Public Health Zhejiang University School of Medicine Department of Hepatobiliary and Pancreatic Surgery First Affiliated Hospital Zhejiang University School of Medicine Department of Vascular Surgery First Affiliated Hospital Zhejiang University School of Medicine

AIM: To optimize the perfusates used for hypothermicmachine perfusion(HMP).METHODS: Sprague-Dawley rats were assigned randomly to three groups(n = 12 per group) that received either saline, University of Wisconsin coldstorage solution(UW) or histidine-tryptophan-ketoglutarate solution(HTK) as the perfusate. Each group was divided into two subgroups: static cold storage(SCS) and HMP(n = 6 per subgroup). The liver graft was retrieved according to the method described by Kamada. For the SCS group, the graft was directly placed into cold perfusate(0-4?℃) for 6 h after liver isolation while the portal vein of the graft was connected to the perfusion machine for the HMP group. Then the perfusates were collected at different time points for analysis of aspartate aminotransferase(AST), alanine transaminase(ALT) and lactate dehydrogenase(LDH) levels. Liver tissues were obtained for evaluation of histology, dry/wet weight(D/W) ratio, and malondialdehyde(MDA) and adenosine-triphosphate(ATP) levels. The portal vein pressure and velocity were monitored in real time in all HMP subgroups.RESULTS: Comparison of HMP and SCS: Regardless of the perfusate, HMP improved the architecture of donor graft in reducing the congestion around sinusoids and central vein and maintaining sinusoid lining in morphology; HMP improved liver function in terms of ALT, AST and LDH, especially during the 3-6 h period(SCS vs HMP using saline: ALT3, 225.00 ± 105.62 vs 49.50 ± 18.50, P = 0.047; LDH3, 1362.17 ± 563.30 vs 325.75 ± 147.43, P = 0.041; UW: LDH6, 2880.14 ± 948.46 vs 2135.00 ± 174.27, P = 0.049; HTK, AST6, 307.50 ± 52.95 vs 185.20 ± 20.46, P = 0.041); HMP decreased MDA level(saline, 2.79 ± 0.30 vs 1.09 ± 0.09, P = 0.008; UW, 3.01 ± 0.77 vs 1.23 ± 0.68, P = 0.005; HTK, 3.30 ± 0.52 vs 1.56 ± 0.22, P = 0.006). Comparison among HMP subgroups: HTK showed less portal vein resistance than UW and saline(vs saline, 3.41 ± 0.49 vs 5.00 ± 0.38, P < 0.001; vs UW, 3.41 ± 0.49 vs 4.52 ± 0.63, P = 0.007); UW reduced edema most efficiently(vs saline, 0.68 ± 0.0

关键词： hypothermic machine perfusion Staticcold storage Liver viability Wisconsin cold-storagesolution Histidine-tryptophan-ketoglutarate solution

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Liver transplantation with grafts obtained after cardiac death-current advances in mastering the challenge

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World Journal of Translational Medicine 2014年第2期3卷 58-68页

作者： Fateh Bazerbachi Nazia Selzner John B Seal Markus Selzner Department of Medicine University of Minnesota Department of Medicine University of TorontoMultiorgan Transplant Program Toronto General Hospital Department of Surgery University of Toronto Multiorgan Transplant Program Toronto General Hospital

The scarcity of donor livers has increased the interest in donation after cardiac death(DCD) as an additional pool to expand the availability of organs. However, the initial results of liver transplantation with DCD grafts have been suboptimal due to an increased rate of complications, as well as decreased graft survival. These challenges have led to many developments in DCD donation outcome, as well as basic and translational research. In this article we review the unique characteristics of DCD donors, nuances of DCD organ procurement, the effect of prolonged warm and cold ischemia times, and discuss major studies that compared DCD to donation after brain death liver transplantation, in terms of outcomes and complications. We also review the different methods of donor treatment that has been applied to ameliorate DCD organ outcome, and we discuss the role of machine perfusion techniques in organ reconditioning. We discuss the two major perfusionmodels, namely, hypothermic machine perfusion and normothermic machine perfusion; we compare both methods, and delineate their major differences.

关键词： Transplant hepatology Liver transplantation Organ donation Extended criteria donors Donation after cardiac death Ex-vivo liver perfusion Normothermic machine perfusion hypothermic machine perfusion

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