scholarly journals Deregulation of the Purine Pathway in Pre-Transplant Liver Biopsies Is Associated with Graft Function and Survival after Transplantation

2020 ◽  
Vol 9 (3) ◽  
pp. 711 ◽  
Author(s):  
Jin Xu ◽  
Mohammad Hassan-Ally ◽  
Ana María Casas-Ferreira ◽  
Tommi Suvitaival ◽  
Yun Ma ◽  
...  
Keyword(s):  
Graft Function ◽  
Area Under The Curve ◽  
Adenosine Monophosphate ◽  
Donation After Circulatory Death ◽  
Discrimination Analysis ◽  
Donation After Brain Death ◽  
Early Graft ◽  
Liver Biopsies ◽  
Purine Pathway ◽  
Early Allograft Dysfunction

The current shortage of livers for transplantation has increased the use of marginal organs sourced from donation after circulatory death (DCD). However, these organs have a higher incidence of graft failure, and pre-transplant biomarkers which predict graft function and survival remain limited. Here, we aimed to find biomarkers of liver function before transplantation to allow better clinical evaluation. Matched pre- and post-transplant liver biopsies from DCD (n = 24) and donation after brain death (DBD, n = 70) were collected. Liver biopsies were analysed using mass spectroscopy molecular phenotyping. Discrimination analysis was used to parse metabolites differentiated between the two groups. Five metabolites in the purine pathway were investigated. Of these, the ratios of the levels of four metabolites to those of urate differed between DBD and DCD biopsies at the pre-transplantation stage (q < 0.05). The ratios of Adenosine monophosphate (AMP) and adenine levels to those of urate also differed in biopsies from recipients experiencing early graft function (EGF) (q < 0.05) compared to those of recipients experiencing early allograft dysfunction (EAD). Using random forest, a panel consisting of alanine aminotransferase (ALT) and the ratios of AMP, adenine, and hypoxanthine levels to urate levels predicted EGF with area under the curve (AUC) of 0.84 (95% CI (0.71, 0.97)). Survival analysis revealed that the metabolite classifier could stratify six-year survival outcomes (p = 0.0073). At the pre-transplantation stage, a panel composed of purine metabolites and ALT could improve the prediction of EGF and survival.

scholarly journals The purine pathway in liver tissue biopsies from donors for transplantation is associated to immediate graft function and survival

2019 ◽  
Author(s):  
Jin Xu ◽  
Mohammad Hassan-Ally ◽  
Ana María Casas-Ferreira ◽  
Tommi Suvitaival ◽  
Yun Ma ◽  
...  
Keyword(s):  
Liver Function ◽  
Clinical Data ◽  
Liver Tissue ◽  
Graft Function ◽  
List Type ◽  
Purine Metabolites ◽  
Data Driven Approach ◽  
Liver Biopsies ◽  
Purine Pathway ◽  
Underlying Mechanisms

AbstractBackground & AimsThe current shortage of livers for transplantation has increased the use of organs sourced from donation after circulatory death (DCD). These organs are prone to higher incidence of graft failure, but the underlying mechanisms are largely unknown. Here we aimed to find biomarkers of liver function before transplantation to better inform clinical evaluation.MethodsMatched pre- and post-transplant liver biopsies from DCD (n=24) and donation after brain death (DBD, n=70) were collected. Liver biopsies were analysed using mass spectroscopy molecular phenotyping. First, a discrimination analysis DCD vs DBD was used to parse metabolites associated to DCD. Then a data-driven approach was used to predict Immediate Graft Function (IGF). The metabolites were tested in models to predict survival.ResultsFive metabolites in the purine pathway were selected and investigated. The ratios of: adenine monophosphate (AMP), adenine, adenosine and hypoxanthine to urate, differed between DBD and DCD biopsies at pre-transplantation stage (q<0.05). The ratios of AMP and adenine to urate also differed in biopsies from recipients undergoing IGF (q<0.05). Using random forest a panel composed by alanine aminotransferase (ALT) and AMP, adenine, hypoxanthine ratio to urate predicted IGF with AUC 0.84 (95% CI [0.71, 0.97]). In comparison AUC 0.71 (95%CI [0.52, 0.90]) was achieved by clinical measures. Survival analysis revealed that the metabolite classifier could stratify 6-year survival outcomes (p = 0.0073) while clinical data and donor class could not.ConclusionsAt liver pre-transplantation stage, a panel composed of purine metabolites and ALT in tissue could improve prediction of IGF and survival.Lay summaryNew liver function biomarkers could help clinicians assess livers before transplantation. Purines are small molecules that are found in healthy livers, and in this work we found that their levels changed critically in livers from cardiac death donors. Measuring them before transplantation improved the prediction of the liver’s immediate graft function.Graphic abstractHighlightsThe ratios of purine metabolites to urate differ between DCD and DBD in liver tissue at pre-transplantation.The ratios of purine metabolites to urate and ALT pre-transplantation can improve prediction of IGF after transplantation.Purine metabolites ratios to urate stratified 6-year survival outcome better than clinical data and donor class.

scholarly journals Donor des-gamma-carboxy prothrombin positivity is a risk factor for poor early graft function in liver transplantation

1998 ◽  
Vol 11 (2) ◽  
pp. 143-146 ◽  
Author(s):  
Taketoshi Suehiro ◽  
Peter Boros ◽  
Sukru Emre ◽  
Patricia A. Sheiner ◽  
Stephen Guy ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Risk Factor ◽  
Graft Function ◽  
Early Graft

Impact of selected factors on early graft function in patients after renal transplantation

2003 ◽  
Vol 35 (6) ◽  
pp. 2167-2169 ◽  
Author(s):  
J Sienko ◽  
M Wisniewska ◽  
M Ostrowski ◽  
K Ciechanowski ◽  
K Safranow ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Graft Function ◽  
Early Graft

Donation after Brain Death versus Donation after Circulatory Death: Lung Donor Management Issues

2018 ◽  
Vol 39 (02) ◽  
pp. 138-147 ◽  
Author(s):  
Bronwyn Levvey ◽  
Kovi Levin ◽  
Miranda Paraskeva ◽  
Glen Westall ◽  
Gregory Snell
Keyword(s):  
Brain Death ◽  
Ex Vivo ◽  
Scoring Systems ◽  
Donation After Circulatory Death ◽  
Donor Pool ◽  
Ex Vivo Lung Perfusion ◽  
Conversion Rates ◽  
Donor Lung ◽  
Donation After Brain Death ◽  
Circulatory Death

AbstractLung transplantation (LTx) has traditionally been limited by a lack of suitable donor lungs. With the recognition that lungs are more robust than initially thought, the size of the donor pool of available lungs has increased dramatically in the past decade. Donation after brain death (DBD) and donation after circulatory death (DCD) lungs, both ideal and extended are now routinely utilized. DBD lungs can be damaged. There are important differences in the public's understanding, legal and consent processes, intensive care unit strategies, lung pathophysiology, logistics, and potential-to-actual donor conversion rates between DBD and DCD. Notwithstanding, the short- and long-term outcomes of LTx from any of these DBD versus DCD donor scenarios are now similar, robust, and continue to improve. Large audits suggest there remains a large untapped pool of DCD (but not DBD) lungs that may yet further dramatically increase lung transplant numbers. Donor scoring systems that might predict the donor conversion rates and lung quality, the role of ex vivo lung perfusion as an assessment and lung resuscitation tool, as well as the potential of donor lung quality biomarkers all have immense promise for the clinical field.

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