Extended Criteria Donors Research Articles

Extended Donor Criteria Outcomes in Adult Congenital Heart Disease Patients Undergoing Heart Transplantation in the United States.

Background: There are very few published outcomes for the use of extended criteria donor (ECD) organs in adult congenital heart disease (ACHD) patients undergoing cardiac transplantation. We investigated outcomes with the use of ECD organs in this population. We hypothesized that ECD organs may be safely used in this population in patients who are younger and carry less vascular and renal disease than the general cardiac transplant population. Methods: United Network of Organ Sharing data from all ACHD heart transplant recipients between October 18, 2018, and September 30, 2023, was analyzed. Patients were grouped by ECD transplantation. The primary outcome of interest was one-year survival. Secondary outcomes included length of stay, posttransplant stroke, retransplantation, kidney transplantation, dialysis, pacemaker implantation, and rejection. Results: Extended criteria donor organs were utilized in 39.1% (200/512) of ACHD heart transplantation cases. There was marked regional variation in the use of ECD organs. Extended criteria donor criteria in this population were solely met by ischemic time ≥4 h in 89.5% (179/200) of cases. Transplantation with ECD donors was associated with lower survival (one-year survival 82.76% vs 90.62%). A multivariate Cox regression analysis suggested a hazard ratio of 1.96 with the use of these organs. Conclusion: Compared with organs accepted under traditional donor criteria, ECD organs appear to compromise short- and long-term survival in ACHD transplant candidates.

REGULATION OF ADIPONECTIN AND RESISTIN IN LIVER TRANSPLANTATION PROTECTS GRAFTS FROM EXTENDED-CRITERIA DONORS.

The donor shortage increases liver transplantation (LT) waiting lists, making it crucial to consider extended criteria donors (ECDs), such as steatotic donors after brain death (DBDs) or cardiocirculatory death (DCDs). Nevertheless, steatosis, brain death, and cardiocirculatory death are key risk factors for poor LT outcomes. We investigated the role and therapeutical usefulness of several adipocytokines to protect such grafts from ECD. Sprague rats with nutritionally-induced steatosis were used in an experimental LT model with grafts from DBD or DCD. Adiponectin, resistin, and visfatin were measured, pharmacologically modulated, and effects on liver injury were assessed. Visfatin played no role under conditions of neither DBD nor DCD LT. Brain death increased adiponectin and reduced resistin. Adiponectin harmed steatotic and nonsteatotic DBD grafts, via a resistin-dependent mechanism; restraining adiponectin increased resistin, reducing damage. Resistin treatment protected both types of DBD grafts, whereas suppressing it increased damage. This adiponectin-resistin pathway was dependent on PKC. In DCD LT, adiponectin and resistin were not modified in nonsteatotic grafts, but reduced in steatotic ones. Adiponectin or resistin treatments protected steatotic grafts: hepatic adiponectin activated AMPK; hepatic resistin increased PI3k-Akt. Concomitant administration of both adipocytokines increased both signaling pathways, intensifying protection. Therefore, pharmacological modulation of adiponectin and resistin resulted in therapies that potentially might be translated to clinical studies to improve surgical outcomes for LT from ECD.

Ice-cold storage or controlled hypothermia to preserve marginal grafts in high-risk heart transplantation.

To evaluate the effectiveness of the Paragonix SherpaPak cardiac transport system (PSP) compared to the standard ice-cold storage (ICS) in extended-criteria donor grafts implanted in high-risk recipients. Data of all HTx at the University Centers of Udine and Bologna, between January 2020 and December 2023, employing extended-criteria donors in high-risk HTx conditions were retrospectively analyzed. Patient outcomes and complications after HTx were assessed. Endomyocardial biopsies were performed in donor hearts immediately after retrieval (T0), before implantation (T1) and at reperfusion (T2) to evaluate signs of myocardial damage. Overall, 90 patients who had heart transplantation (HTx) with a donor graft preserved with either ICS (n = 60) or PSP (n = 30) were included in the study. The 30-day mortality was 3% in both groups (p = 0.99), and 1-year survival 90% and 88% (p = 0.89) for recipients transplanted with PSP and ICS preserved grafts. Rates of moderate-to-severe graft dysfunction and bradi-arrhythmias for PSP and ICS groups were 7% versus 20% (p = 0.08), and 3% versus 15% (p = 0.09). Histologically, severe degrees of cellular and endothelial damage were absent in all PSP grafts while severe degree of contraction bands were higher in ICS hearts at T2. In high-risk donor-recipient matching, donor heart preservation with PSP seems to show a tendency toward better graft protection.

Outcomes of donation after circulatory death (DCD) and ex-vivo lung perfusion (EVLP) lung transplantation

BackgroundDonation after circulatory death (DCD) and ex-vivo lung perfusion (EVLP) have been adopted to expand the donor pool in lung transplantation, but outcomes data have been conflicting. This study explores mid-term outcomes of DCD lung transplantation in the modern era, with a focus on EVLP and risk factors for graft failure. MethodsThe United Network for Organ Sharing (UNOS) database was queried for adult lung transplants from 1/1/2015 to 3/1/2023. Loss to follow-up, multiorgan and prior lung transplants were excluded. DCD vs DBD (donation after brain death) lung transplants were compared, with subgroup analysis +/- EVLP. Outcomes were survival and postoperative complications. Overall survival was analyzed separately for an early era (2015-2018) and modern era (2019-2023). ResultsThe study included 1103 DCD (221 with EVLP, and 882 without) and 17973 donation after brain death (DBD) lung transplants (524 with EVLP, and 17449 without). Median follow-up was 3 years. DCD donors were less likely to be CDC high risk (19.3% vs 24.1%, p<0.001), have purulence on bronchoscopy (13.3% vs 18.3%, p<0.001) or infiltrates on chest x-ray (66.7% vs 67.8%, p=0.013). EVLP was more likely to be used for DCD transplants (20.0% vs 2.9%, p<0.001).After transplant, DCD recipients were more likely to be reintubated (24.3% vs 18.5%, p<0.001) and require ECMO within 72 hours (14.9% vs 7.8%, p<0.001), and DCD donation was an independent risk factor for these complications on multivariable logistic regression. Overall survival did not differ significantly between DCD and DBD transplants on adjusted survival analysis in the early or modern era (p=0.774 and p=0.468 respectively). On multivariable Cox regression, DCD and EVLP were not independent risk factors for mortality.On subgroup analysis, the DCD+EVLP cohort had significantly worse survival in the modern era, which remained significant after adjusting for donor and recipient factors (p=0.005). EVLP was an independent risk factor for graft failure in the DCD cohort (HR 1.33, 95% CI 1.00-1.77, p=0.047), but did not significantly affect DBD graft survival (p=0.870). Risk factors for graft failure and mortality in the DCD+EVLP cohort included pulmonary hypertension (HR 77.5, 95% CI 6.15-979, p<0.001), transfusion prior to transplant (HR 2.60, 95% CI 1.07-6.31, p=0.035), elevated creatinine (HR 2.82, 95% CI 1.34-5.90, p=0.006), and higher allocation score (HR 1.02, 95% CI 1.00-1.04, p=0.017) ConclusionStudy findings suggest increased risks of mortality and perioperative complications following transplantation with DCD lungs that have undergone EVLP. DCD lung transplantation without EVLP confers equivalent survival but with some increase in perioperative complications. Further investigation and careful recipient selection is warranted to optimize the use of these extended criteria donors in the modern era.

Pushing the Survival Bar Higher: Two Decades of Innovation in Lung Transplantation.

Survival after lung transplantation has significantly improved during the last two decades. The refinement of the already existing extracorporeal life support (ECLS) systems, such as extracorporeal membrane oxygenation (ECMO), and the introduction of new techniques for donor lung optimization, such as ex vivo lung perfusion (EVLP), have allowed the extension of transplant indication to patients with end-stage lung failure after acute respiratory distress syndrome (ARDS) and the expansion of the donor organ pool, due to the better evaluation and optimization of extended-criteria donor (ECD) lungs and of donors after circulatory death (DCD). The close monitoring of anti-HLA donor-specific antibodies (DSAs) has allowed the early recognition of pulmonary antibody-mediated rejection (AMR), which requires a completely different treatment and has a worse prognosis than acute cellular rejection (ACR). As such, the standardization of patient selection and post-transplant management has significantly contributed to this positive trend, especially at high-volume centers. This review focuses on lung transplantation after ARDS, on the role of EVLP in lung donor expansion, on ECMO as a principal cardiopulmonary support system in lung transplantation, and on the diagnosis and therapy of pulmonary AMR.

P.191: The outcomes of the deceased donor kidney transplantation using extended criteria donor.

P.191: The outcomes of the deceased donor kidney transplantation using extended criteria donor.

Multinational Analysis of Marginal Liver Grafts Based on the Eurotransplant Extended Donor Criteria.

To evaluate the outcome of marginal liver grafts based on the Eurotransplant extended criteria donor (ECD) criteria. Eurotransplant uses a broad definition of ECD criteria (age >65 years, steatosis >40%, body mass index >30kg/m 2 , intensive care unit stay >7 days, donation after circulatory death, and certain laboratory parameters) for allocating organs to recipients who have consented to marginal grafts. Historically, marginal liver grafts were associated with increased rates of dysfunction. Retrospective cohort analysis using the German Transplant Registry and the U.S. Scientific Registry of Transplant Recipients (SRTR) from 2006 to 2016. Results were validated with recent SRTR data (2017-2022). Donors were classified according to the Eurotransplant ECD criteria, donation after circulatory death was excluded. Data were analyzed with cutoff prediction, binomial logistic regression, and multivariate Cox regression. The study analyzed 92,330 deceased brain-dead donors (87% SRTR) and 70,374 transplants (87% SRTR) in adult recipients. Predominant ECD factors were donor age in Germany (30%) and body mass index in the United States (28%). Except for donor age, grafts meeting ECD criteria were not associated with impaired 1 or 3-year survival. Cutoffs had little to no predictive value for 30-day graft survival (area under the receiver operating curve: 0.49-0.52) and were nominally higher for age (72 vs 65 years) in Germany as compared with those defined by current Eurotransplant criteria. The outcome of transplanted grafts from higher risk donors was nearly equal to standard donors with Eurotransplant criteria failing to predict survival of marginal grafts. Modifying ECD criteria could improve graft allocation and potentially expand the donor pool.

Extended Criteria Donor Use in Lung Transplants From Donation After Controlled Circulatory Death

BackgroundMost institutions apply the criteria for controlled donation after cardiac death (cDCD) lung retrieval identical to the criteria for donation after brain death (DBD). The availability of extended criteria donor (ECD) in lung transplants from cDCD remains unclear. MethodsThe United Network for Organ Sharing (UNOS) database was queried for adult lung transplants from cDCD, from May 03, 2005, to March 15, 2022. ECDs were defined by one or more items at variance from standard criteria: age 55 years or more, PaO2:FiO2 300 or less, smoking 20 pack-years or more, diabetes, or purulent secretions upon bronchoscopy. Recipients were divided into the standard criteria donor (SCD) group and the ECD group, and assessed for short- and long-term survival and postoperative events. ResultsAmong 827 records, the SCD and ECD group showed no differences in 5-year (P = .56) survival. No significant differences were found in 30-day, 90-day, 1-year mortality and postoperative outcomes before discharge, whether in length of hospital stay, rate of ventilator support for >48 hours or reintubation, incidence of grade 3 PGD 72 hours posttransplant, acute rejection, or dialysis. None of the 5 donor factors used as criteria for lung retrieval was independently associated with cDCD recipient survival. ConclusionsUsing donor lungs that extend the DBD criteria may be a safe strategy in cDCD lung transplantation. However, the current criteria may not be a perfect fit for cDCD lung retrieval. The specific DCD criteria for standard lung retrieval need to be determined.

Revolutionizing Donor Heart Procurement: Innovations and Future Directions for Enhanced Transplantation Outcomes.

Heart failure persists as a critical public health challenge, with heart transplantation esteemed as the optimal treatment for patients with end-stage heart failure. However, the limited availability of donor hearts presents a major obstacle to meeting patient needs. In recent years, the most groundbreaking progress in heart transplantation has been in donor heart procurement, significantly expanding the donor pool and enhancing clinical outcomes. This review comprehensively examines these advancements, including the resurgence of heart donation after circulatory death and innovative recovery and evaluation technologies such as normothermic machine perfusion and thoraco-abdominal normothermic regional perfusion. Additionally, novel preservation methods, including controlled hypothermic preservation and hypothermic oxygenated perfusion, are evaluated. The review also explores the use of extended-criteria donors, post-cardiopulmonary resuscitation donors, and high-risk donors, all contributing to increased donor availability without compromising outcomes. Future directions, such as xenotransplantation, biomarkers, and artificial intelligence in donor heart evaluation and procurement, are discussed. These innovations promise to address current limitations and optimize donor heart utilization, ultimately enhancing transplantation success. By identifying recent advancements and proposing future research directions, this review aims to provide insights into advancing heart transplantation and improving patient outcomes.

Are we on track to increase organ utilization? An analysis of machine perfusion preservation for liver transplantation in the United States.

Efforts to improve the quality of marginal grafts for transplantation are essential. Machine perfusion preservation appears as a promising solution. The United Network for Organ Sharing (UNOS) database was queried for deceased liver donor records between 2016 and 2022. The primary outcome of interest was the organ nonutilization rate. Long-term graft and patient survival among extended criteria donors (ECDs) were also analyzed. During the study period, out of 54 578 liver grafts recovered for transplant, 5085 (9.3%) were nonutilized. Multivariable analysis identified normothermic machine perfusion (NMP) preservation as the only predictor associated with a reduction in graft nonutilization (OR = 0.12; 95% CI = 0.06-0.023, p < 0.001). Further analysis of ECD grafts that were transplanted revealed comparable 1-,2- and 3-years graft survival (89%/88%/82% vs. 90%/85%/81%, p = 0.60), and patient survival (92%/91%/84% vs. 92%/88%/84%, p = 0.65) between grafts that underwent MP vs. those who did not, respectively. Liver nonutilization rates in the United States are at an all-time high. Available data, most likely including cases from clinical trials, showed that NMP reduced the odds of organ nonutilization by 12% among the entire deceased donor pool and by 16% among grafts from ECD. Collective efforts and further evidence reflecting day-to-day clinical practice are needed to fully reach the potential of MP for liver transplant.

Liver function maximum capacity test during normothermic regional perfusion predicts graft function after transplantation

PurposeIn an effort to reduce waitlist mortality, extended criteria donor organs, including those from donation after circulatory death (DCD), are being used with increasing frequency. These donors carry an increased risk for postoperative complications, and balancing donor-recipient risks is currently based on generalized nomograms. Abdominal normothermic regional perfusion (aNRP) enables individual evaluation of DCD organs, but a gold standard to determine suitability for transplantation is lacking. This study aimed to incorporate individualized and predictive measurements of the liver maximum capacity (LiMAx) test to objectively grade liver function during aNRP and prevent post-op complications.MethodsaNRP was performed to salvage 18 DCD liver grafts, otherwise discarded. Continuous variables were presented as the median with the interquartile range.ResultsThe liver function maximum capacity (LiMAx) test was successfully performed within the aNRP circuit in 17 aNRPs (94%). Donor livers with good lactate clearance during aNRP demonstrated significantly higher LiMAx scores (396 (301–451) µg/kg/h versus those who did not 105 (70–158) µg/kg/h; P = 0.006). This was also true for manifesting stress hyperglycemia > 20 mmol/l (P = 0.032). LiMAx score correlated with alanine aminotransferase (ALT; R = − 0.755) and aspartate transaminase (AST; R = − 0.800) levels during perfusion and distinguished livers that were selected for transplantation (397 (346–453) µg/kg/h) from those who were discarded (155 (87–206) µg/kg/h; P < 0.001). Twelve livers were accepted for transplantation, blinded for LiMAx results, and all had LiMAx scores of > 241 µg/kg/h. Postoperatively, LiMAx during aNRP displayed correlation with 24-h lactate levels.ConclusionsThis study shows for the first time the feasibility to assess liver function during aNRP in individual donor livers. LiMAx presents an objective tool to predict donor liver function and risk of complications in the recipient, thus enabling individualized matching of donor livers for an individual recipient. The LiMAx test may present a valuable test for the prediction of donor liver function, preventing post-transplant complication, and personalizing the selection of donor livers for individual recipients.

Potential kidney donors among patients with out-of-hospital cardiac arrest and a termination of resuscitation rule

ImportanceUncontrolled donation after circulatory determination of death (uDCD) has been developed and can serve as a source of kidneys for transplantation, especially when considering patients that meet extended criteria donation (ECD). ObjectiveThis study assessed the theorical size and characteristics of the potential pool of kidney transplants from uDCD with standard criteria donation (SCD) and ECD among patients who meet Termination of Resuscitation (TOR) criteria following Out of Hospital Cardiac Arrest (OHCA). Methods and participantsThis study focused on adult patients experiencing unexpected OHCA, who were prospectively enrolled in the Parisian registry from May 16th, 2011, to December 31st, 2020. ResultsDuring the study period, EMS attempted resuscitation for 19,976 OHCA patients, of which 64.5% (12,890) had no return of spontaneous circulation. Among them, 47.4% (9,461) had TOR criteria, representing no chance of survival, and from them, 8.8% (1,764) met SCD criteria and could be potential organ donors and 33.6% (6,720) met ECD for kidney donors. The mean potential number per year of uDCD candidates with SCD and ECD remain stable respectively around 98 (±10.8) and 672 (±103.8) cases per year. Elderly patients (≥65 y.o.) represented 61.2% (n = 5,763/9,461) of patients who met TOR and 100% (5763/5763) of patients who could have matched both ECD criteria and TOR. Conclusion and relevanceImplementing uDCD program including SCD and ECD for kidney transplantation among OHCA cases quickly identified by the TOR, holds significant potential to substantially broaden the pool of organ donors. These programs could offer a viable solution to address the pressing burden of kidney shortage, particularly benefiting elderly recipients who may otherwise face prolonged waiting times and limited access to suitable organs.

Coronary Angiography During Ex-Situ Heart Perfusion in a Porcine Model.

Heart transplantation is the gold standard treatment for advanced heart failure. The procurement of extended criteria donors (ECD) increases due to the current organ shortage. Coronary angiography is recommended in ECD at risk for coronary artery disease but is not systematically performed. These hearts are, therefore, either declined for transplant or procured without screening for coronary artery disease. Coronary angiography during normothermic ex-situ heart perfusion (NESP) could be an interesting approach to enhance the rate of ECD procurement and to reduce the risk of primary graft failure in the absence of coronary angiography in ECD. The present protocol aims to provide material details along with optimal imaging views for coronary angiography during NESP. Reproducible angiographic views were observed, including one dedicated to the right coronary artery, two for the left anterior descending artery, two for the circumflex artery, and a spider view. Continuous lactate extraction was observed in all procedures with a final median concentration of 1.10 mmol/L (0.61-1.75 mmol/L) two hours after coronary angiography, consistent with myocardial viability. The median contrast agent volume used for ex-situ imaging of the isolated perfused heart was 48 mL (38-108 mL). This protocol was reproducible for coronary artery imaging and did not impair myocardial viability during NESP.

Recent solid-phase microextraction-based analytical approaches for the profiling of biliary bile acids in pre-transplant assessments of liver grafts subjected to normothermic ex vivo liver perfusion

BackgroundLiver transplantation is the definitive treatment for end-stage liver failure, but the scarcity of donor organs remains a significant challenge. Leveraging organs from extended criteria donors (ECD) offers a potential avenue to address worldwide shortages, though these organs are more susceptible to post-reperfusion injury. This study explores the use of normothermic ex vivo liver perfusion (NEVLP) as a method for organ preservation – an approach that sustains liver metabolism and facilitates pre-transplant assessments of organ viability via bile analysis. The focal point of this study revolves on the development of analytical methods for determining the bile acid profile throughout the peritransplantation period as a potential indicator of liver function and viability. ResultsThe study optimized and validated a high-throughput analytical method to quantify selected bile acids in bile samples using a thin-film microextraction-liquid chromatography-mass spectrometry (TFME-LC-MS) platform. Furthermore, it introduced a solid-phase microextraction-microfluidic open interface-mass spectrometry (SPME-MOI-MS) method for rapid direct analysis of bile acid isobar groups. In the animal study, discernible variations in the concentrations of specific bile acids were observed between donors after circulatory death (DCD) and heart-beating donors (HBD), particularly following normothermic perfusion and reperfusion. Noteworthy fluctuations in individual bile acid concentrations were observed throughout the entire organ transplantation process, with taurocholic acid (TCA), glycocholic acid (GCA), and glycochenodeoxycholic acid (GCDCA) emerging as promising indicators of organ quality. The efficacy of the SPME-MOI-MS platform in corroborating these trends highlights its potential for real-time bile acid analysis during liver transplantation procedures. SignificanceOur findings underscore the efficacy of NEVLP in tandem with advanced bile acid analysis methods as a reliable strategy for pre-transplant assessments of organ viability, potentially increasing the use of ECD organs and reducing organ shortages. The ability to monitor bile acid profiles in real-time provides crucial insights into liver function and ischemic injury, making significant strides in improving transplant outcomes and patient survival rates.

Quality Assessment by Bile Composition in Normothermic Machine Perfusion of Rat Livers.

Background: The persistent challenge of organ scarcity in liver transplantation leads to an escalating dependence on organs obtained from extended criteria donors (ECD). Normothermic machine perfusion (NMP) is used for improved preservation. Due to the mimicked invivo conditions during normothermic machine perfusion, the liver is metabolically active, which allows quality assessment during perfusion. Bile seems to be of rising interest in clinical studies, as it is easily collectible for analysis. As there are currently no data on biliary bile acids during NMP, the primary objective of this study was to use our experimental rodent NMP model to assess changes in bile composition through organ damage during perfusion to inform clinical evaluation of donor organs during NMP. Methods: Thirty livers from male Sprague-Dawley rats in five groups underwent 6 h of NMP using either erythrocyte-supplemented DMEM or Steen solution, with or without 30 min of warm ischemia time (WIT). We conducted regular measurements of AST, ALT, LDH, and urea levels in the perfusate at 3-hour intervals. Bile samples were analyzed for biliary pH, LDH, and gamma glutamyltransferase, as well as biliary bile acids via mass spectrometry and UHPLC. Results: Compared with regular livers, liver injury parameters were significantly higher in our donation after circulatory death (DCD) model. Bile production was significantly reduced in livers exposed to WIT, and the bile showed a significantly more alkaline pH. This correlated with the concentration of total bile acids, which was significantly higher in livers experiencing WIT. However, regular livers produced a higher total amount of biliary bile acids during perfusion. Taurocholic acid and its metabolites were most prominent. Secondary bile acids were significantly reduced during perfusion due to the missing enterohepatic circulation. Conclusions: WIT-induced liver injury affects bile composition within our small-animal NMP model. We hypothesize this phenomenon to be attributed to the energy-driven nature of bile secretion, potentially explaining why DCD livers produce less, yet more concentrated, bile. Our results may inform clinical studies, in which biliary bile acids might have a potential as a quantifiable viability marker in human NMP liver transplantation studies.

Oxygenated versus non-oxygenated flush out during deceased donor liver procurement: The first proof-of-concept study in humans.

Liver transplantation is used for treating end-stage liver disease, fulminant hepatitis, and oncological malignancies and organ shortage is a major limiting factor worldwide. The use of grafts based on extended donor criteria have become internationally accepted. Oxygenated machine perfusion technologies are the most recent advances in organ transplantation; however, it is only applied after a period of cold ischemia. Due to its high cost, we aimed to use a novel device, OxyFlush®, based on oxygenation of the preservation solution, applied during liver procurement targeting the maintenance of ATP during static cold storage (SCS). Twenty patients were randomly assigned to the OxyFlush or control group based on a 1:1 ratio. In the OxyFlush group, the perfusion solution was oxygenated with OxyFlush® device while the control group received a non-oxygenated solution. Liver and the common bile duct (CBD) biopsies were obtained at three different time points. The first was at the beginning of the procedure, the second during organ preparation, and the third after total liver reperfusion. Biopsies were analyzed, and adenosine triphosphate (ATP) levels and histological scores of the liver parenchyma and CBD were assessed. Postoperative laboratory tests were performed. OxyFlush® was able to maintain ATP levels during SCS and improved the damage caused by the lack of oxygen in the CBD. However, OxyFlush® did not affect laboratory test results and histological findings of the parenchyma. We present a novel low-cost device that is feasible and could represent a valuable tool in organ preservation during SCS.

Advancements in Predictive Tools for Primary Graft Dysfunction in Liver Transplantation: A Comprehensive Review.

Orthotopic liver transplantation stands as the sole curative solution for end-stage liver disease. Nevertheless, the discrepancy between the demand and supply of grafts in transplant medicine greatly limits the success of this treatment. The increasing global shortage of organs necessitates the utilization of extended criteria donors (ECD) for liver transplantation, thereby increasing the risk of primary graft dysfunction (PGD). Primary graft dysfunction (PGD) encompasses early allograft dysfunction (EAD) and the more severe primary nonfunction (PNF), both of which stem from ischemia-reperfusion injury (IRI) and mitochondrial damage. Currently, the only effective treatment for PNF is secondary transplantation within the initial post-transplant week, and the occurrence of EAD suggests an elevated, albeit still uncertain, likelihood of retransplantation urgency. Nonetheless, the ongoing exploration of novel IRI mitigation strategies offers hope for future improvements in PGD outcomes. Establishing an intuitive and reliable tool to predict upcoming graft dysfunction is vital for early identification of high-risk patients and for making informed retransplantation decisions. Accurate diagnostics for PNF and EAD constitute essential initial steps in implementing future mitigation strategies. Recently, novel methods for PNF prediction have been developed, and several models for EAD assessments have been introduced. Here, we provide an overview of the currently scrutinized predictive tools for PNF and EAD evaluation strategies, accompanied by recommendations for future studies.

Effect of Donor Cigarette Smoking in Kidney Transplantation: Re-Evaluation of Long-Term Outcomes.

Cigarette smoking is a common risk factor associated with negative long-term outcomes in kidney transplant recipients. However, whether donor smoking decreases graft longevity or negatively impacts recipient survival after kidney transplantation remains unknown. Therefore, this study aims to investigate the long-term outcome in patients who received a kidney graft from a deceased smoking or non-smoking donor. A total of 580 patients were divided into two groups: patients who received a graft from a smoking donor (n = 276) and those who received a graft from a non-smoking donor (n = 304). Analysis of demographic factors showed that the non-smoking cohort was older, had more extended criteria donors and longer warm ischemia times. The primary composite endpoint of patient and graft survival was better in the smoking donor cohort when analyzed using Kaplan-Meier method but not when controlled for covariates in multivariate analyses. These findings do not support a previously reported negative impact of deceased donor smoking on kidney transplant recipients. Thus, the underlying results should not be interpreted in favor of a positive donor smoking history, but rather remind the transplant community that donor smoking should not be considered as a deciding factor in refusing an otherwise acceptable kidney graft.

Viability assessment and transplantation of extended criteria donor liver grafts using normothermic machine perfusion

BackgroundThe scarcity of available liver grafts necessitates the use of organs from extended criteria donors, a practice associated with an increased risk of graft failure. A notable percentage of deceased donor liver allografts are rejected due to subjective criteria. Normothermic machine perfusion holds promise for introducing objective parameters into this decision-making process. The aim of this study was to compare the outcomes of standard criteria and extended criteria donor allografts after liver transplantation, following viability assessment, using normothermic machine perfusion. MethodsLiver allografts preserved by normothermic machine perfusion before liver transplantation at the University Hospital of Münster were retrospectively analyzed. Organs were stratified according to the Eurotransplant Donor Risk Index. In total, 101 liver grafts were included in this study and divided into 2 groups: (1) standard criteria donors with a Donor Risk Index <1.8 (DRI-low) and (2) extended criteria donors with a Donor Risk Index ≥1.8 (DRI-high). ResultsAn increased risk profile of donor livers, as assessed by the Eurotransplant Donor Risk Index, did not correlate with patient or graft survival. High-risk liver grafts were effectively transplanted into recipients with different risk levels after viability assessment by normothermic machine perfusion. However, the recipients’ model for end-stage liver disease scores showed a significant association with both overall patient and graft survival. ConclusionThe use of normothermic machine perfusion for viability assessment allows safe transplantation of high-risk donor livers and effectively addresses the disparity between donor liver availability and transplantation demand.

Donor plasma VEGF-A as a biomarker for myocardial injury and primary graft dysfunction after heart transplantation

BackgroundVascular endothelial growth factor (VEGF)-A is an angiogenic and proinflammatory cytokine with profound effects on microvascular permeability and vasodilation. Several processes may induce VEGF-A expression in brain-dead organ donors. However, it remains unclear whether donor VEGF-A is linked to adverse outcomes after heart transplantation. MethodsWe examined plasma VEGF-A levels from 83 heart transplant donors as well as the clinical data of these donors and their respective recipients operated between 2010 and 2016. The donor plasma was analyzed using Luminex-based Multiplex and confirmed with a single-target ELISA. Based on donor VEGF-A plasma levels, the recipients were divided into three equal-sized groups (low VEGF <500 ng/L, n=28; moderate VEGF 500-3000 ng/L, n=28; and high VEGF >3000 ng/L, n=27). Biochemical and clinical parameters of myocardial injury as well as heart transplant and kidney function were followed-up for one year, while rejection episodes, development of cardiac allograft vasculopathy, and mortality were monitored for five years. ResultsBaseline parameters were comparable between the donor groups, except for age, where median ages of 40, 45, and 50 were observed for low, moderate, and high donor plasma VEGF levels groups, respectively, and therefore donor age was included as a confounding factor. High donor plasma VEGF-A levels were associated with pronounced myocardial injury (TnT and TnI), a higher inotrope score, and a higher incidence of primary graft dysfunction in the recipient after heart transplantation. Furthermore, recipients with allografts from donors with high plasma VEGF-A levels had a longer length of stay in the intensive care unit and the hospital, and an increased likelihood for prolonged renal replacement therapy. ConclusionsOur findings suggest that elevated donor plasma VEGF-A levels were associated with adverse outcomes in heart transplant recipients, particularly in terms of myocardial injury, primary graft dysfunction, and long-term renal complications. Donor VEGF-A may serve as a potential biomarker for predicting these adverse outcomes and identifying extended donor criteria.