Perfusate Analysis During Dual Hypothermic Oxygenated Machine Perfusion of Liver Grafts: Correlations With Donor Factors and Early Outcomes.
Alanine Transaminase
/ analysis
Aspartate Aminotransferases
/ analysis
Cold Temperature
Female
Graft Survival
Humans
Hydrogen-Ion Concentration
L-Lactate Dehydrogenase
/ analysis
Liver Transplantation
/ adverse effects
Male
Middle Aged
Organ Preservation
/ methods
Perfusion
/ methods
Retrospective Studies
Tissue Donors
Journal
Transplantation
ISSN: 1534-6080
Titre abrégé: Transplantation
Pays: United States
ID NLM: 0132144
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
pubmed:
10
8
2020
medline:
7
10
2020
entrez:
10
8
2020
Statut:
ppublish
Résumé
Liver graft viability assessment has long been considered a limit of hypothermic oxygenated machine perfusion (HOPE). Aim of this study was assessing correlations of easily available perfusate parameters (PP) (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, glucose, lactate, and pH) with graft features and outcome. In the period October 2018-February 2020, perfusate samples were obtained every 30 minutes during 50 dual-HOPE (D-HOPE) procedures. Correlations of PP with graft factors, 90-day graft loss, early allograft dysfunction (EAD), L-GrAFT score, acute kidney injury, and comprehensive complication index were analyzed using Pearson coefficient, receiver-operating characteristics analysis and by univariable and multivariable regression. Median D-HOPE time was 122 minutes. All parameters were normalized to liver weight. Only macrovesicular steatosis (MaS) significantly impacted PP levels and slope. Grafts with ≥30% MaS exhibited significantly different PP values and slope. Graft loss and EAD rate were 2% (n = 1) and 26% (n = 13). All PP except lactate correlated with EAD, 90-minute alanine aminotransferase showing the highest area under the receiver-operating characteristics curve (0.84). However, at multivariable analysis, the only factor independently associated with EAD was MaS (odds ratio, 5.44; confidence interval, 1.05-28.21; P = 0.04). Ninety minutes lactate dehydrogenase had the strongest correlation with L-GrAFT (R = 0.70; P < 0.001). PP correlated poorly with comprehensive complication index and grades 2-3 acute kidney injury rate. PP were predictive of graft function after transplant, but their association with graft survival and clinical outcomes requires further evaluation. MaS influenced levels of PP and was the only independent predictor of EAD.
Sections du résumé
BACKGROUND
Liver graft viability assessment has long been considered a limit of hypothermic oxygenated machine perfusion (HOPE). Aim of this study was assessing correlations of easily available perfusate parameters (PP) (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, glucose, lactate, and pH) with graft features and outcome.
METHODS
In the period October 2018-February 2020, perfusate samples were obtained every 30 minutes during 50 dual-HOPE (D-HOPE) procedures. Correlations of PP with graft factors, 90-day graft loss, early allograft dysfunction (EAD), L-GrAFT score, acute kidney injury, and comprehensive complication index were analyzed using Pearson coefficient, receiver-operating characteristics analysis and by univariable and multivariable regression.
RESULTS
Median D-HOPE time was 122 minutes. All parameters were normalized to liver weight. Only macrovesicular steatosis (MaS) significantly impacted PP levels and slope. Grafts with ≥30% MaS exhibited significantly different PP values and slope. Graft loss and EAD rate were 2% (n = 1) and 26% (n = 13). All PP except lactate correlated with EAD, 90-minute alanine aminotransferase showing the highest area under the receiver-operating characteristics curve (0.84). However, at multivariable analysis, the only factor independently associated with EAD was MaS (odds ratio, 5.44; confidence interval, 1.05-28.21; P = 0.04). Ninety minutes lactate dehydrogenase had the strongest correlation with L-GrAFT (R = 0.70; P < 0.001). PP correlated poorly with comprehensive complication index and grades 2-3 acute kidney injury rate.
CONCLUSIONS
PP were predictive of graft function after transplant, but their association with graft survival and clinical outcomes requires further evaluation. MaS influenced levels of PP and was the only independent predictor of EAD.
Identifiants
pubmed: 32769628
doi: 10.1097/TP.0000000000003398
pii: 00007890-202009000-00028
doi:
Substances chimiques
L-Lactate Dehydrogenase
EC 1.1.1.27
Aspartate Aminotransferases
EC 2.6.1.1
Alanine Transaminase
EC 2.6.1.2
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
1929-1942Références
Patrono D, Surra A, Catalano G, et al. Hypothermic oxygenated machine perfusion of liver grafts from brain-dead donors. Sci Rep. 2019; 9:9337
Schlegel A, Muller X, Kalisvaart M, et al. Outcomes of DCD liver transplantation using organs treated by hypothermic oxygenated perfusion before implantation. J Hepatol. 2019; 70:50–57
van Rijn R, Karimian N, Matton APM, et al. Dual hypothermic oxygenated machine perfusion in liver transplants donated after circulatory death. Br J Surg. 2017; 104:907–917
van Rijn R, van Leeuwen OB, Matton APM, et al. Hypothermic oxygenated machine perfusion reduces bile duct reperfusion injury after transplantation of donation after circulatory death livers. Liver Transpl. 2018; 24:655–664
Ravaioli M, De Pace V, Angeletti A, et al. Hypothermic oxygenated new machine perfusion system in liver and kidney transplantation of extended criteria donors: First Italian Clinical Trial. Sci Rep. 2020; 10:6063
Schlegel A, Kron P, de Oliveira ML, et al. Reply to “Is single portal vein perfusion the best approach for machine preservation of liver grafts?”. J Hepatol. 2016; 64:1195–1196
Guarrera JV, Henry SD, Samstein B, et al. Hypothermic machine preservation in human liver transplantation: the first clinical series. Am J Transplant. 2010; 10:372–381
Guarrera JV, Henry SD, Samstein B, et al. Hypothermic machine preservation facilitates successful transplantation of “orphan” extended criteria donor livers. Am J Transplant. 2015; 15:161–169
Muller X, Schlegel A, Kron P, et al. Novel real-time prediction of liver graft function during hypothermic oxygenated machine perfusion before liver transplantation. Ann Surg. 2019; 270:783–790
Feng S, Goodrich NP, Bragg-Gresham JL, et al. Characteristics associated with liver graft failure: the concept of a donor risk index. Am J Transplant. 2006; 6:783–790
Ali JM, Davies SE, Brais RJ, et al. Analysis of ischemia/reperfusion injury in time-zero biopsies predicts liver allograft outcomes. Liver Transpl. 2015; 21:487–499
Suzuki S, Toledo-Pereyra LH, Rodriguez FJ, et al. Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury. Modulating effects of FK506 and cyclosporine. Transplantation. 1993; 55:1265–1272
Olthoff KM, Kulik L, Samstein B, et al. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl. 2010; 16:943–949
Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012; 120:c179–c184
Agopian VG, Harlander-Locke MP, Markovic D, et al. Evaluation of early allograft function using the liver graft assessment following transplantation risk score model. JAMA Surg. 2018; 153:436–444
Slankamenac K, Graf R, Barkun J, et al. The comprehensive complication index: a novel continuous scale to measure surgical morbidity. Ann Surg. 2013; 258:1–7
Bujang MA, Adnan TH. Requirements for minimum sample size for sensitivity and specificity analysis. J Clin Diagn Res. 2016; 10:YE01–YE06
McNeish DM. Using lasso for predictor selection and to assuage overfitting: a method long overlooked in behavioral sciences. Multivariate Behav Res. 2015; 50:471–484
Dutkowski P, Oberkofler CE, Slankamenac K, et al. Are there better guidelines for allocation in liver transplantation? A novel score targeting justice and utility in the model for end-stage liver disease era. Ann Surg. 2011; 254:745–53. discussion 753
Guy AJ, Nath J, Cobbold M, et al. Metabolomic analysis of perfusate during hypothermic machine perfusion of human cadaveric kidneys. Transplantation. 2015; 99:754–759
Guzzi F, Knight SR, Ploeg RJ, et al. A systematic review to identify whether perfusate biomarkers produced during hypothermic machine perfusion can predict graft outcomes in kidney transplantation. Transpl Int. 2020; 33:590–602
Hoogland ER, de Vries EE, Christiaans MH, et al. The value of machine perfusion biomarker concentration in DCD kidney transplantations. Transplantation. 2013; 95:603–610
Johnson RW, Anderson M, Taylor RM, et al. Significance of perfusate lactic acidosis in cadaveric renal transplantation. Br Med J. 1973; 1:391–395
Khalid U, Ablorsu E, Szabo L, et al. MicroRNA-21 (miR-21) expression in hypothermic machine perfusate may be predictive of early outcomes in kidney transplantation. Clin Transplant. 2016; 30:99–104
Kosieradzki M, Danielewicz R, Kwiatkowski A, et al. Early function of kidneys stored by continuous hypothermic pulsatile perfusion can be predicted using a new “viability index.” Transplant Proc. 2002; 34:541–543
Moers C, Varnav OC, van Heurn E, et al. The value of machine perfusion perfusate biomarkers for predicting kidney transplant outcome. Transplantation. 2010; 90:966–973
Parikh CR, Hall IE, Bhangoo RS, et al. Associations of perfusate biomarkers and pump parameters with delayed graft function and deceased donor kidney allograft function. Am J Transplant. 2016; 16:1526–1539
Daemen JW, Oomen AP, Janssen MA, et al. Glutathione S-transferase as predictor of functional outcome in transplantation of machine-preserved non-heart-beating donor kidneys. Transplantation. 1997; 63:89–93
de Vries B, Snoeijs MG, von Bonsdorff L, et al. Redox-active iron released during machine perfusion predicts viability of ischemically injured deceased donor kidneys. Am J Transplant. 2006; 6:2686–2693
de Vries EE, Hoogland ER, Winkens B, et al. Renovascular resistance of machine-perfused DCD kidneys is associated with primary nonfunction. Am J Transplant. 2011; 11:2685–2691
Jochmans I, Moers C, Smits JM, et al. The prognostic value of renal resistance during hypothermic machine perfusion of deceased donor kidneys. Am J Transplant. 2011; 11:2214–2220
Bellini MI, Charalampidis S, Herbert PE, et al. Cold pulsatile machine perfusion versus static cold storage in kidney transplantation: a single centre experience. Biomed Res Int. 2019; 2019:7435248
Jochmans I, Pirenne J. Graft quality assessment in kidney transplantation: not an exact science yet! Curr Opin Organ Transplant. 2011; 16:174–179
von Moos S, Akalin E, Mas V, et al. Assessment of organ quality in kidney transplantation by molecular analysis and why it may not have been achieved, yet. Front Immunol. 2020; 11:833
De Beule J, Jochmans I. Kidney perfusion as an organ quality assessment tool-are we counting our chickens before they have hatched? J Clin Med. 2020; 9:879
Kim WR, Flamm SL, Di Bisceglie AM, et al.; Public Policy Committee of the American Association for the Study of Liver Disease. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology. 2008; 47:1363–1370
Farhana A, Lappin SL. Biochemistry, Lactate Dehydrogenase (LDH). 2020, Treasure Island, FL:: StatPearls
Watson CJE, Jochmans I. From “gut feeling” to objectivity: machine preservation of the liver as a tool to assess organ viability. Curr Transplant Rep. 2018; 5:72–81
Schlegel A, Graf R, Clavien PA, et al. Hypothermic oxygenated perfusion (HOPE) protects from biliary injury in a rodent model of DCD liver transplantation. J Hepatol. 2013; 59:984–991
Caraceni P, Nardo B, Domenicali M, et al. Ischemia-reperfusion injury in rat fatty liver: role of nutritional status. Hepatology. 1999; 29:1139–1146
Bessems M, Doorschodt BM, Kolkert JL, et al. Preservation of steatotic livers: a comparison between cold storage and machine perfusion preservation. Liver Transpl. 2007; 13:497–504
Kron P, Schlegel A, Mancina L, et al. Hypothermic oxygenated perfusion (HOPE) for fatty liver grafts in rats and humans J Hepatol. 2017; 68:P82–P91
Monbaliu D, Liu Q, Libbrecht L, et al. Preserving the morphology and evaluating the quality of liver grafts by hypothermic machine perfusion: a proof-of-concept study using discarded human livers. Liver Transpl. 2012; 18:1495–1507
Boteon YL, Boteon APCS, Attard J, et al. Ex situ machine perfusion as a tool to recondition steatotic donor livers: troublesome features of fatty livers and the role of defatting therapies. A systematic review. Am J Transplant. 2018; 18:2384–2399
Fukumori T, Ohkohchi N, Tsukamoto S, et al. The mechanism of injury in a steatotic liver graft during cold preservation. Transplantation. 1999; 67:195–200
van Gulik TM. New concepts in liver preservation: how the pendulum sways back. Liver Transpl. 2009; 15:1–3
Okamura Y, Hata K, Uemoto S. Reply to “representing subnormothermic machine perfusion in fatty livers: the complete picture?” Am J Transplant. 2017; 17:1423–1424
Vairetti M, Ferrigno A, Carlucci F, et al. Subnormothermic machine perfusion protects steatotic livers against preservation injury: a potential for donor pool increase? Liver Transpl. 2009; 15:20–29
Boteon YL, Attard J, Boteon APCS, et al. Manipulation of lipid metabolism during normothermic machine perfusion: effect of defatting therapies on donor liver functional recovery. Liver Transpl. 2019; 25:1007–1022