A successful strategy for achieving minimal cold ischemia time for Donation after Circulatory Death in Belfast City Hospital

Background and objectivesIncreased donor age is one of the most important risk factors for delayed graft function (DGF), and previous studies suggest that the harmful effect of cold ischemia time is increased in kidneys from older donors. Our aim was to study the association of increased donor age and cold ischemia time with the risk of delayed graft function in a large cohort kidney transplants from the current era.Design, setting, participants, & measurementsThe Scientific Registry of Transplant Recipients was used for this observational, retrospective registry analysis to identify all deceased donor kidney transplantations in the United States between 2010 and September 2018, who were on dialysis pretransplantation (n=90,810). The association of donor age and cold ischemia time with the risk of DGF was analyzed in multivariable models adjusted for recipient characteristics (age, race, sex, diabetes, calculated panel-reactive antibodies, pretransplant dialysis duration) and donor characteristics (cause of death, sex, race, body mass index, creatinine, donation after circulatory death status, history of hypertension, and HLA mismatch).ResultsCold ischemia time and donor age were independently associated with the risk of DGF, but the risk of DGF was not statistically significantly lower in donor age categories between 50 and 64 years, compared with donors ≥65 years. The harmful association of cold ischemia time was not higher in kidneys from older donors in any age category, not even among donation after circulatory death donors. When donor risk was assessed with kidney donor profile index, although a statistically significant interaction with cold ischemia time was found, no practically meaningful increase in cold-ischemia susceptibility of kidneys with a high kidney donor profile index was found.ConclusionsWe were unable to demonstrate an association between donor age and DGF. The association of longer cold ischemia time with the risk of DGF was not magnified in older or more marginal donors.

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Donor Death Category Is an Effect Modifier Between Cold Ischemia Time and Post-transplant Graft Function in Deceased-Donor Kidney Transplant Recipients

Frontiers in Medicine ◽

10.3389/fmed.2021.743085 ◽

2021 ◽

Vol 8 ◽

Author(s):

You Luo ◽

Zhanwen Dong ◽

Xiao Hu ◽

Zuofu Tang ◽

Jinhua Zhang ◽

...

Keyword(s):

Brain Death ◽

Graft Function ◽

Potential Effect ◽

Cold Ischemia Time ◽

Cold Ischemia ◽

Effect Modifier ◽

Ischemia Time ◽

Post Transplant ◽

Donation After Brain Death ◽

Circulatory Death

Objectives: We aimed to analyze the effect of cold ischemia time (CIT) on post-transplant graft function through mixed-effect model analysis to reduce the bias caused by paired mate kidneys.Methods: We reviewed all kidney transplantation records from 2015 to 2019 at our center. After applying the exclusion criteria, 561 cases were included for analysis. All donor characteristics, preservation and matching information, and recipient characteristics were collected. Transplant outcomes included delayed graft function (DGF) and estimated glomerular filtration rate (eGFR). Generalized linear mixed models were applied for analysis. We also explored potential effect modifiers, namely, donor death category, expanded criteria donors, and donor death causes.Results: Among the 561 cases, 79 DGF recipients developed DGF, and 15 recipients who died after surgery were excluded from the eGFR estimation. The median stable eGFR of the 546 recipients was 60.39 (47.63, 76.97) ml/min/1.73 m2. After adjusting for confounding covariates, CIT had a negative impact on DGF incidence [odds ratio = 1.149 (1.006, 1.313), P = 0.041]. In the evaluation of the impact on eGFR, the regression showed that CIT had no significant correlation with eGFR [β = −0.287 (−0.625, 0.051), P = 0.096]. When exploring potential effect modifiers, only the death category showed a significant interaction with CIT in the effect on eGFR (Pinteraction = 0.027). In the donation after brain death (DBD) group, CIT had no significant effect on eGFR [β = 0.135 (−0.433, 0.702), P = 0.642]. In the donation after circulatory death/donation after brain death followed by circulatory death (DCD/DBCD) group, CIT had a significantly negative effect on eGFR [β= −0.700 (−1.196, −0.204), P = 0.006]. Compared to a CIT of 0–6 h, a CIT of 6–8 or 8–12 h did not decrease the post-transplant eGFR. CIT over 12 h (12–16 h or over 16 h) significantly decreased eGFR. With the increase in CIT, the regenerated eGFR worsened (Ptrend = 0.011).Conclusion: Considering the effect of paired mate kidneys, the risk of DGF increased with prolonged CIT. The donor death category was an effect modifier between CIT and eGFR. Prolonged CIT did not reduce the eGFR level in recipients from DBDs but significantly decreased the eGFR in recipients from DCDs/DBCDs. This result indicates the potential biological interaction between CIT and donor death category.

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Clinical Implications of Donor Warm and Cold Ischemia Time in Donor After Circulatory Death Liver Transplantation

Liver Transplantation ◽

10.1002/lt.25453 ◽

2019 ◽

Vol 25 (9) ◽

pp. 1342-1352 ◽

Cited By ~ 9

Author(s):

Flavio Paterno ◽

James V. Guarrera ◽

Koffi Wima ◽

Tayyab Diwan ◽

Madison C. Cuffy ◽

...

Keyword(s):

Liver Transplantation ◽

Clinical Implications ◽

Cold Ischemia Time ◽

Cold Ischemia ◽

Ischemia Time ◽

Circulatory Death

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The endogenous capacity to produce proinflammatory mediators by the ex vivo human perfused lung

Intensive Care Medicine Experimental ◽

10.1186/s40635-020-00343-x ◽

2020 ◽

Vol 8 (1) ◽

Author(s):

Aleksandra Leligdowicz ◽

James T. Ross ◽

Nicolas Nesseler ◽

Michael A. Matthay

Keyword(s):

Ex Vivo ◽

Cold Ischemia Time ◽

Cold Ischemia ◽

Experimental Conditions ◽

Ischemia Time ◽

Proinflammatory Mediators ◽

Donor Lung ◽

Perfused Lung ◽

Lung Response ◽

Percent Weight Gain

Abstract Background The ex vivo human perfused lung model has enabled optimizing donor lungs for transplantation and delineating mechanisms of lung injury. Perfusate and airspace biomarkers are a proxy of the lung response to experimental conditions. However, there is a lack of studies evaluating biomarker kinetics during perfusion and after exposure to stimuli. In this study, we analyzed the ex vivo-perfused lung response to three key perturbations: exposure to the perfusion circuit, exogenous fresh whole blood, and bacteria. Results Ninety-nine lungs rejected for transplantation underwent ex vivo perfusion. One hour after reaching experimental conditions, fresh whole blood was added to the perfusate (n = 55). Two hours after reaching target temperature, Streptococcus pneumoniae was added to the perfusate (n = 42) or to the airspaces (n = 17). Perfusate and airspace samples were collected at baseline (once lungs were equilibrated for 1 h, but before blood or bacteria were added) and 4 h later. Interleukin (IL)-6, IL-8, angiopoietin (Ang)-2, and soluble tumor necrosis factor receptor (sTNFR)-1 were quantified. Baseline perfusate and airspace biomarker levels varied significantly, and this was not related to pre-procurement PaO2:FiO2 ratio, cold ischemia time, and baseline alveolar fluid clearance (AFC). After 4 h of ex vivo perfusion, the lung demonstrated a sustained production of proinflammatory mediators. The change in biomarker levels was not influenced by baseline donor lung characteristics (cold ischemia time, baseline AFC) nor was it associated with measures of experimental epithelial (final AFC) or endothelial (percent weight gain) injury. In the presence of exogenous blood, the rise in biomarkers was attenuated. Lungs exposed to intravenous (IV) bacteria relative to control lungs demonstrated a significantly higher rise in perfusate IL-6. Conclusions The ex vivo-perfused lung has a marked endogenous capacity to produce inflammatory mediators over the course of short-term perfusion that is not significantly influenced by donor lung characteristics or the presence of exogenous blood, and only minimally affected by the introduction of systemic bacteremia. The lack of association between biomarker change and donor lung cold ischemia time, final alveolar fluid clearance, and experimental percent weight gain suggests that the maintained ability of the human lung to produce biomarkers is not merely a marker of lung epithelial or endothelial injury, but may support the function of the lung as an immune cell reservoir.

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IMPACT OF COLD ISCHEMIA TIME ON RENAL ALLOGRAFT OUTCOME FROM YOUNG DONORS

Transplantation Journal ◽

10.1097/01.tp.0000331701.83319.b0 ◽

2008 ◽

Vol 86 (Supplement) ◽

pp. 364

Author(s):

D Hernández ◽

S Estupiñán ◽

G Pérez Suárez ◽

M Rufino ◽

J M. González-Posada ◽

...

Keyword(s):

Renal Allograft ◽

Cold Ischemia Time ◽

Cold Ischemia ◽

Ischemia Time ◽

Allograft Outcome

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Interaction of Endogenous Proinflammatory Mediators on the Function of the Ex Vivo Perfused Human lung

10.21203/rs.3.rs-33089/v1 ◽

2020 ◽

Author(s):

Aleksandra Leligdowicz ◽

James T. Ross ◽

Nicolas Nesseler ◽

Michael A. Matthay

Keyword(s):

Ex Vivo ◽

Cold Ischemia Time ◽

Cold Ischemia ◽

Experimental Conditions ◽

Ischemia Time ◽

Proinflammatory Mediators ◽

Donor Lung ◽

Perfused Lung ◽

Lung Response ◽

Percent Weight Gain

Abstract Background The ex vivo human perfused lung model has enabled optimizing donor lungs for transplantation and delineating mechanisms of lung injury. Perfusate and airspace biomarkers are a proxy of the lung response to experimental conditions. However, there is a lack of studies evaluating biomarker kinetics during perfusion and after exposure to stimuli. In this study we analyzed the ex vivo perfused lung response to three key perturbations: exposure to the perfusion circuit, exogenous fresh whole blood, and bacteria. Results 99 lungs rejected for transplantation underwent ex vivo perfusion. One hour after reaching experimental conditions, fresh whole blood was added to the perfusate (n=55). Two hours after reaching target temperature, Streptococcus pneumoniae was added to the perfusate (n=42) or to the airspaces (n=17). Perfusate and airspace samples were collected at baseline (once lungs were equilibrated for 1 hour, but before blood or bacteria were added) and 4 hours later. Interleukin (IL)-6, IL-8, Angiopoietin (Ang)-2, and soluble tumor necrosis factor receptor (sTNFR)-1 were quantified. Baseline perfusate and airspace biomarker levels varied significantly, and this was not related to pre-procurement PaO2:FiO2 ratio, cold ischemia time, and baseline alveolar fluid clearance (AFC). After 4 hours of ex vivo perfusion, the lung demonstrated a sustained production of proinflammatory mediators. The change in biomarker levels was not influenced by baseline donor lung characteristics (cold ischemia time, baseline AFC) nor was it associated with measures of experimental epithelial (final AFC) or endothelial (percent weight gain) injury. In the presence of exogenous blood, the rise in biomarkers was attenuated. Lungs exposed to intravenous (IV) bacteria relative to control lungs demonstrated a significantly higher rise in perfusate IL-6. Conclusions The ex vivo perfused lung has a marked endogenous capacity to generate inflammatory responses over the course of short-term perfusion. The lack of association between biomarker change and donor lung cold ischemia time as well as final alveolar fluid clearance and experimental percent weight gain suggests that the maintained ability to produce biomarkers is not merely a marker of lung epithelial or endothelial injury but may support the lung’s role as an immune cell reservoir.

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Polyomavirus nephropathy: Risk analysis in paired renal Transplant recipients

Brazilian Journal of Transplantation ◽

10.53855/bjt.v19i3.110 ◽

2016 ◽

Vol 19 (3) ◽

pp. 6-9

Author(s):

André Barros Albuquerque Esteves ◽

Luiz Roberto Sousa Ulisses ◽

Leonardo Figueiredo Camargo ◽

Gabriel Giollo Rivelli ◽

Marcos Vinicius de Sousa ◽

...

Keyword(s):

Risk Factors ◽

Renal Transplant ◽

Acute Rejection ◽

Immunosuppressive Therapy ◽

Renal Transplant Recipients ◽

Cold Ischemia Time ◽

Hla Matching ◽

Cold Ischemia ◽

Ischemia Time ◽

Related Risk

Polyomavirus allograft nephropathy (PVAN) has a negative impact on allograft function and survival. Analysis of paired kidneys from same donor can help to understand the role of recipient risk factors for PVAN. This analysis can also define donor related risk factors. Purpose: To identify recipient related risk factors for PVAN. Patients and Methods: Transversal cohort of 24 renal transplant patients in regular outpatient clinic follow up. Twelve patients with PVAN and their paired controls (recipients from same donor) without decoy cells in cytology were included in this analysis. Medical records were analyzed for demographic data, information of transplant and post-transplant data (acute rejection, renal function, immunosuppression). Results: Groups were comparable for initial immunosuppressive therapy based on basiliximab induction, tacrolimus, mycophenolate and steroids. Etiology of end-stage renal disease, race, age, HLA matching and delayed graft function considered as risk factors were also similar between patients with or without PVAN. However, PVAN group had more male patients (91.6 vs. 66.6%, PVAN versus control, p<0.05), higher incidence of biopsy proven acute rejection (41.6% vs. 8.3%, PVAN vs. control, p<0.05) and a trend to shorter cold ischemia time (15.6+6.2 versus 19.7+5.0, p=0.06). Conclusion: In this series, there were no significant differences in immunosuppressive therapy, age and HLA matching between patients with or without PVAN common risk factors. The only factors to be considered in this series were older age and a trend to shorter cold ischemia time in PVAN patients.

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