Differential donor management of pediatric vs adult organ donors and potential impact on pediatric lung transplantation.

BACKGROUND: Despite clinical progress over time, a shortage of suitable donor organs continues to limit solid organ transplantation around the world. Lungs are the organs most likely to be assessed as unsuitable during donor management among all transplantable organs. Although the number of lung transplants performed in children is limited, death on the wait list remains a barrier to transplant success for many potential transplant candidates. Optimizing organ donor management can yield additional organs for transplant candidates. METHODOLOGY: We accessed the Donor Management Goal (DMG) Registry to evaluate the efficiency and efficacy of donor management in the procurement of lungs for transplantation. Further, we stratified donors by age and compared pediatric age cohorts to adult cohorts with respect to attainment of donor management target goals and successful pathway to transplantation. We utilized recipient data from the Organ Procurement Transplantation Network (OPTN) to put this data into context. The DMG bundle consists of nine physiologic parameters chosen as end-points guiding donor management for potential organ donors. The number of parameters fulfilled has been regarded as an indication of efficacy of donor management. RESULTS: We noted a markedly lower number of organ donors in the pediatric age group compared to adults. On the other hand, the number of donors greatly exceeds the number of infants, children and adolescents who undergo lung transplantation. Organs transplanted per donor peaks in the adolescent age group. At initial donor referral, DMG bundle attainment is lower in all age groups and improves during donor management. With respect to oxygenation, there is less overall improvement in younger donors compared to older donors during donor management. When donors who yield lungs for transplantation are compared to those whose lungs were not transplanted, oxygenation improved more substantially during donor management. Furthermore, improved oxygenation correlated with the total number of organs transplanted per donor. CONCLUSIONS: In the face of continued wait list mortality on the pediatric lung transplant wait list, the number of young donors may not be a limiting factor. We believe that this dataset provides evidence that management of young pediatric donors is not as consistent or efficient as the management of older donors, potentially limiting the number of life-saving organs for pediatric lung transplant candidates. Across all ages, optimizing donor lung management may increase the potential to transplant multiple other organs.

Expanded Criteria Donors.

The expanded criteria donor is any donor over the age of 60 years or a donor over the age of 50 years with 2 of the following 3 items: (1) history of high blood pressure, (2) serum creatinine ≥1.5 mg/dL, and (3) death due to stroke. To accept an expanded criteria donor kidney may significantly decrease the amount of time a person waits for transplant but requires written informed consent from the recipient. Although expanded criteria donor kidneys have predictably shorter outcomes than standard criteria donors, the exact risk is unknown. At 5 years follow-up, 50% of expanded criteria donor kidneys are still working. Regardless of donor status of these kidneys as expanded criteria or standard criteria, the transplant recipients have higher survival rates compared with candidates who remain on the wait list. The success rate may be increased when a perfusion pump is used to preserve the kidneys. Sometimes the function of a single kidney from an expanded criteria donor is deemed insufficient. In this situation, a pair of marginally functioning kidneys may be transplanted as a dual-kidney transplant. This dual transplant option offers acceptable outcomes as good as a single-kidney transplant with normal function and can effectively address the shortage of donor organs. The use of a perfusion pump allows the clinician to decide whether or not to use a particular expanded criteria donor kidney. Expanded criteria donors may be justified by meticulous selection of each donor for recipients, along with more sophisticated surgical techniques to maximize the kidney donor pool.

Trends in Survival for Pediatric Transplantation.

OBJECTIVES: Progress in pediatric transplantation measured in the context of waitlist and posttransplant survival is well documented but falls short of providing a complete perspective for children and their families. An intent-to-treat analysis, in which we measure survival from listing to death regardless of whether a transplant is received, provides a more comprehensive perspective through which progress can be examined. METHODS: Univariable and multivariable Cox regression was used to analyze factors impacting intent-to-treat survival in 12 984 children listed for heart transplant, 17 519 children listed for liver transplant, and 16 699 children listed for kidney transplant. The Kaplan-Meier method and log-rank test were used to assess change in waitlist, posttransplant, and intent-to-treat survival. Wait times and transplant rates were compared by using χ2 tests. RESULTS: Intent-to-treat survival steadily improved from 1987 to 2017 in children listed for heart (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.96-0.97), liver (HR 0.95, 95% CI 0.94-0.97), and kidney (HR 0.97, 95% CI 0.95-0.99) transplant. Waitlist and posttransplant survival also improved steadily for all 3 organs. For heart transplant, the percentage of patients transplanted within 1 year significantly increased from 1987 to 2017 (60.8% vs 68.7%); however, no significant increase was observed in liver (68.9% vs 72.5%) or kidney (59.2% vs 62.7%) transplant. CONCLUSIONS: Intent-to-treat survival, which is more representative of the patient perspective than individual metrics alone, steadily improved for heart, liver, and kidney transplant over the study period. Further efforts to maximize the donor pool, improve posttransplant outcomes, and optimize patient care while on the waitlist may contribute to future progress.

Overexpression of the SARS-CoV-2 receptor angiotensin converting enzyme 2 in cardiomyocytes of failing hearts.

Hospitalized patients who die from Covid-19 often have pre-existing heart disease. The SARS-CoV-2 virus is dependent on the ACE2 receptor to be able to infect cells. It is possible that the strong link between cardiovascular comorbidities and a poor outcome following a SARS-CoV-2 infection is sometimes due to viral myocarditis. The aim was to examine the expression of ACE2 in normal hearts and hearts from patients with terminal heart failure. The ACE2 expression was measured by global quantitative proteomics and RT-qPCR in left ventricular (LV) tissue from explanted hearts. Immunohistochemistry was used to examine ACE2 expression in cardiomyocytes, fibroblasts and endothelial cells. In total, tissue from 14 organ donors and 11 patients with terminal heart failure were included. ACE2 expression was 2.6 times higher in 4 hearts from patients with terminal heart failure compared with 6 healthy donor hearts. The results were confirmed by immunohistochemistry where more than half of cardiomyocytes or fibroblasts showed expression of ACE2 in hearts from patients with terminal heart failure. In healthy donor hearts ACE2 was not expressed or found in few fibroblasts. A small subpopulation of endothelial cells expressed ACE2 in both groups. Upregulated ACE2 expression in cardiomyocytes may increase the risk of SARS-CoV-2 myocarditis in patients with heart failure.

Marking DMEK Grafts Using Bandage Contact Lens Interface Technique: Doubling the Utilization During the Acute Shortage of Donor Corneas.

PURPOSE: The purpose of this study was to describe a novel bandage contact lens (BCL) interface technique for marking the Descemet membrane endothelial keratoplasty (DMEK) graft so that a single donor cornea can be used effectively for 2 recipients during acute shortage. METHODS: This was a retrospective comparative case series. In group A, 37 eyes underwent DMEK using a graft marked by the ?BCL interface technique" that was compared with 49 conventional DMEK grafts marked through the stromal window (group B). In group A, a resized BCL with a central 3-mm hole with the concavity up was placed between the stroma and peeled-off DM. This BCL with DM was flipped for S-stamping on the DM side. Final trephination was performed on a second Teflon block. The remaining anterior lamellar tissues of group A were used on the same day for other keratoplasty procedures. Endothelial cell density (ECD) and endothelial cell loss between the 2 groups were compared after 3 and 6 months. RESULTS: The ECD at 3 months in group A (n = 35) versus group B (n = 45) was 2228 ± 270/mm2 versus 2302 ± 254/mm2 (P = 0.48), and the ECD at 6 months (n = 23 and 22) was 2058 ± 324/mm2 versus 2118 ± 260/mm2 (P = 0.72). The corresponding endothelial cell loss was 23.3% ± 6.8% versus 20.3% ± 6.1% (P = 0.18) at 3 months and 29.1% ± 8.4% versus 26.7% ± 8.0% (P = 0.34) at 6 months. Among anterior tissues of group A, 17 (45.9%) were used for deep anterior lamellar keratoplasty, 18 (48.6%) were used for larger therapeutic and tectonic grafts, and 2 were used as keratoprosthesis carriers. Donor detachment rate (8.6% vs. 8.9%) was similar in both groups without primary graft failures. CONCLUSIONS: The BCL interface technique is a simple and safe technique for stamping DMEK grafts. Anterior corneal tissues can be used for additional keratoplasties during donor shortage.

Marginal donors and organ shortness: concomitant surgical procedures during heart transplantation: a literature review.

Heart transplantation represents the gold standard for end-stage heart failure. However, due to the increasing demand and the shortage of available organs, donor supply remains the main limitation. Marginal donor hearts in high-risk candidates who do not meet standard listing criteria are the only alternative when life expectancy is limited, but their use is still debated. Surgical correction of detected coronary lesions or valvular heart defects allows further enlargement of the number of available organs. In this article, we offer a literature review on this topic and report two marginal donor hearts with angiography evidence of coronary stenosis and preserved ventricular function, which underwent concomitant myocardial revascularization during heart implantation.

Examining Corneal Tissue Exportation Fee and Its Impact on Equitable Allocation.

METHODS: We conducted grounded theory semistructured interviews, purposively inviting participants until themed saturation was met. Sentiment analysis was used to determine opinion. RESULTS: We interviewed n = 92 global eye tissue and eye bank professionals. We determined that corneal tissue, which is exported, costs between US $100 and US $6000 or is provided as gratis. Collectively, interviewees indicated that, globally, there were no fixed fee structures in place, and the fee was influenced by multiple factors on both export and import sides. They indicated that ultimately corneas were allocated based on the importers' ability to pay the price determined by the exporting eye bank. DISCUSSION: Allocation of corneal tissue, which is exported, is influenced by the fees charged by the exporters to meet their bottom line and the funds available to importers. Therefore, export allocation is not equitable, with those who can pay a higher fee, prioritized. Steps to guide and support exporters with the development of fee structures that promote equitable allocation are essential. This will assist both export and import eye bank development, corneal tissue access development, and those awaiting a corneal transplant.

Epidemiology of corneal transplantation before achieving the Zero Queue / Epidemiologia do transplante de córnea antes de atingir a Fila Zero

ABSTRACT Objective: To outline the epidemiological profile of cornea donors and recipients before reaching queue zero. Methods: Epidemiological study, of quantitative approach, with transversal, analytical design, analyzing database records from the Health Secretary of the State of Ceará, from 2013 to 2015. Results: We obtained 1,558 cornea donors and 2,287 cornea recipients from 2013 to 2015. Most donors were male, capital residents, from 21 to 40 years old. Of donated eyeballs, 14.52% were disposed, due to poor condition, infiltration or positive serology. The recipients were predominantly women over 60 years old. The procedures were mostly elective, due to bullous keratopathy (28%). Regarding emergency transplants, ulcer (38.51%) and retransplant (35.14%) were most prevalent. Predominantly, transplants were funded by the Unified Health System. Conclusion: The majority of patients who were submitted to corneal transplantation are senile, especially females, therefore should be cautiously observed. On the other hand, donors are mainly male and young, reflecting the high number of tragic accidents. The surgery for bullous keratopathy is the most frequent among elective transplants, while the ulcer surgery is the main cause of emergency procedures. The fact that most surgeries were financed by the Unified Health System reflects the importance of this system.

RESUMO Objetivo: Traçar o perfil epidemiológico dos doadores e receptores de córnea antes de atingir a Fila Zero. Métodos: Estudo epidemiológico, de abordagem quantitativa, com delineamento transversal e analítico, analisando registros da base de dados da Secretaria de Saúde do Estado do Ceará, de 2013 a 2015. Resultados: Foram obtidos 1.558 doadores de córnea e 2.287 receptores de córnea, de 2013 a 2015. A maioria dos doadores era homem, procedente da capital, de 21 a 40 anos. Dentre os globos oculares doados, 14,52% foram descartados por má condição, infiltração ou sorologia positiva. Os receptores eram predominantemente mulheres acima de 60 anos de idade. Os procedimentos foram majoritariamente eletivos, devido à ceratopatia bolhosa (28%). Já para transplantes de emergência, a úlcera (38,51%) e o retransplante (35,14%) foram os mais prevalentes. Em geral, os transplantes foram custeados pelo Sistema Único de Saúde. Conclusão: A maioria dos pacientes submetidos a transplantes de córnea foram do grupo etário senil, principalmente do sexo feminino, devendo esse grupo ser observado com cautela. Em contrapartida, os doadores eram, principalmente, homens e jovens, refletindo o alto número de pessoas que morrem devido a acidentes trágicos. A cirurgia de ceratopatia bolhosa foi a mais frequente dentre os transplantes eletivos; já a de úlcera foi a principal causa dos procedimentos de emergência. O fato de a maioria das cirurgias ter sido financiada pelo Sistema Único de Saúde reflete a importância desse sistema.

Impacto da pandemia da COVID-19 sobre transplantes de córnea / Impact of COVID-19 pandemic on corneal transplantations

RESUMO Objetivo: Tendo em vista que o sistema visual representa uma via de contaminação para o novo Corona vírus, a The Global Alliance of Eye Bank Association (GAEBA) divulgou um guideline preconizando a prevenção de transmissão do vírus entre o doadores de tecido ocular e o pacientes receptores, o que resultou em uma diminuição no número de ceratoplastias e aumento de filas de espera para transplantes de córnea (TC) em todo o mundo. Nesse sentido, o presente trabalho tem por objetivo analisar a situação do transplante de córnea (TC) no estado de Alagoas durante o primeiro ano de pandemia da COVID-19. Métodos: Trata-se de um estudo analítico, transversal, observacional utilizando dados provenientes de 3 fontes diferentes: Banco de Tecido Ocular Humano de Alagoas (BTO-AL), Registro Brasileiro de Transplantes (RBT) e Agência Nacional de Vigilância Sanitária (ANVISA). Resultados: Durante os últimos seis anos, foram realizados 284 TCs em Alagoas, segundo dados do Banco de Transplante de Olhos do estado (BTO), já segundo a Registro Brasileiro de Transplantes (RBT) foram realizados 451 TCs. A porcentagem de córneas não oriundas do BTO de Alagoas se mostrou crescente até 2019, porém decresceu em 2020, e no primeiro ano de pandemia , apenas 11,66% da necessidade anual estimada foi atendida, sendo o período com menor número de TCs realizados entre os seis anos analisados na pesquisa. Conclusão: O estudo demonstra o declínio na doação e realização de transplantes de córnea durante o primeiro ano da pandemia da COVID-19 em Alagoas.

ABSTRACT Objective: Considering the visual system is one source of contamination for the new coronavirus, The Global Alliance of Eye Bank Association (GAEBA) released a guideline recommending prevention of virus transmission between eye tissue donors and recipients, which resulted in a reduction of keratoplasties and increase in the waiting lists for corneal transplants worldwide. Hence, this work aims to analyze the situation of corneal transplantation in the state of Alagoas, during the first year of COVID-19 pandemic. Methods: This is an analytical, cross-sectional, observational study using data from 3 different sources: Human Eye Tissue Bank of Alagoas (BTO-AL), Brazilian Transplant Registry (RBT) and National Health Surveillance Agency (ANVISA). Results: During the past six years, 284 corneal transplants were performed in Alagoas, according to data from the Eye Transplant Bank (BTO) of the state, whereas according to the Brazilian Transplant Registry (RBT) 451 corneal transplants were performed. The percentage of corneas not coming from the BTO of Alagoas increased until 2019 but dropped in 2020. In the first year of the pandemic, only 11.66% of estimated annual need was met, and this period had the lowest number of corneal transplants performed out of the six years analyzed in the research. Conclusion: The study demonstrated the decline in donation and performance of corneal transplants during the first year of the COVID-19 pandemic in Alagoas.

Trends and Outcomes of Cardiac Transplantation in the Lowest Urgency Candidates.

Background Because of discrepancies between donor supply and recipient demand, the cardiac transplantation process aims to prioritize the most medically urgent patients. It remains unknown how recipients with the lowest medical urgency compare to others in the allocation process. We aimed to examine differences in clinical characteristics, organ allocation patterns, and outcomes between cardiac transplantation candidates with the lowest and highest medical urgency. Methods and Results We performed a retrospective analysis of the United Network for Organ Sharing database. Patients listed for cardiac transplantation between January 2011 and May 2020 were stratified according to status at time of transplantation. Baseline recipient and donor characteristics, waitlist survival, and posttransplantation outcomes were compared in the years before and after the 2018 allocation system change. Lower urgency patients in the old system were older (58.5 versus 56 years) and more likely female (54.4% versus 23.8%) compared with the highest urgency patients, and these trends persisted in the new system (P<0.001, all). Donors for the lowest urgency patients were more likely older, female, or have a history of cytomegalovirus, hepatitis C, or diabetes (P<0.01, all). The lowest urgency patients had longer waitlist times and under the new allocation system received organs from shorter distances with decreased ischemic times (178 miles versus 269 miles, 3.1 versus 3.5 hours; P<0.001, all). There was no difference in posttransplantation survival (P<0.01, all). Conclusions Patients transplanted as lower urgency receive hearts from donors with additional comorbidities compared with higher urgency patients, but outcomes are similar at 1 year.

[Organ donations in Algeria: restrictions and perspectives]. / Le don d´organes en Algérie: limites et perspectives.

The purpose of this study is to highlight the need and the obligation to combine living donation with deceased one, this later is an incomparable source of organ donation, a plea with a triple objective: 1) analyzing the contribution of living donations in terms of numbers, through two elements: the degree of involvement of our medico-surgical competencies and our regulations governing organ donations. 2) Showing that, even though optimized, living donations will always fall short of the needs of our patients and are only part of the solution. 3) The other part is deceased donors: a source of donation which can not be substituted by that of the living donors, and which concerns patients awaiting a vital organ with no possibility of another substitute treatment. Patients are sentenced to death if not transplanted in a few weeks. In this respect, only professionalism and full staff availability can rid us of prejudices which unjustly and systematically overwhelm our society with regard to this type of life-saving donations. In countries promoting and performing this source of donation, a national priority planning network has been developed. This program ensures reliable results, based on universal standards for ethics, recruitment, training and organization. For health authorities of these same countries, the sharing of these organs with others countries is irrational and unreasonable. As long as these organs remain the only life-saving for this type of seriously ill patients, and this source of grafts will be insufficient to meet the needs of all their patients.

Sperm donor lifestyle survey: modifiable risk factors for potential sperm donors.

OBJECTIVES: To examine the association between modifiable lifestyle factors and the main semen parameter values, the number of qualified sperm donors, and to provide some sensible guidance for sperm donors. METHODS: Healthy men screened as potential sperm donors were recruited in the Hunan Province Human Sperm Bank of China from March 2019 to December 2019. Participants were invited to complete interviewer-assisted questionnaires on eleven items of information. Univariate and multivariate analyses were conducted to analyze which lifestyle factors collected by the questionnaire had an impact on the eligibility and main semen parameters of sperm donors. RESULTS: The eligibility of men as sperm donors was strongly influenced by the duration of abstinence (P = 0.002). The rate of eligibility sperm donors increased significantly with the number of days of abstinence. In addition, semen volume increased with abstinence time (P = 0.000). Exercise frequency (P = 0.025) and abstinence time (P = 0.000) were positively correlated with sperm concentration, and masturbation frequency was negatively correlated with sperm concentration (P = 0.013). Progressive sperm motility was significantly affected by abstinence time (P = 0.000) and bedtime (P = 0.047). CONCLUSIONS: Abstinence time was highly associated with semen parameters and donor qualification. Increase the abstinence time before donation may be meaningful in improving the proportion of eligible sperm donors.

Domino transplantation for pediatric liver recipients: Obstacles, challenges, and successes.

BACKGROUND: Domino liver transplantation aims to address the need to increase the liver donor supply. In a domino liver transplant, the domino recipient receives the explanted liver from the recipient of a traditional liver transplant. The domino donor typically requires liver transplant to correct a metabolic disorder; the explanted liver thus has a single gene defect but otherwise normal structure and function. METHODS: In this review, we detail the history of domino liver transplantation, appropriate domino donor indications, the technical advances to the surgical approach, current outcomes, and future opportunities. RESULTS: Development of de novo disease in the domino recipient has relegated adult domino liver transplant to be considered a source of marginal donor livers. However, pediatric domino liver transplant has leveraged certain metabolic disorders, especially maple syrup urine disease, in which the liver enzyme deficiency can be compensated by the systemic presence of sufficient enzyme. Advances in the surgical aspects of assuring adequate length of vasculature have improved the safety of the procedure in both domino donors and recipients. CONCLUSIONS: Pediatric domino liver transplant utilizing domino donors with specific metabolic liver diseases should be considered a viable live donor option for children awaiting liver transplant.

The new world: hematopoietic stem cell transplant during a pandemic.

PURPOSE OF REVIEW: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted every facet of hematopoietic cell transplantation. This article reviews the adjustments to recipient and donor care that occurred in response to this unprecedented event. RECENT FINDINGS: Transplant centers modified algorithms, patient flow, education, and how we provided care. Our donor center partners reworked how donors were evaluated and products delivered to the transplant center. Our professional societies provided guidelines for patient and donor care and rapidly modified these based upon the never-ending stream of new data learned about SARS-CoV-2. Our research organizations provided rapid analyses to ensure the care modifications necessitated did not have a profound negative impact on our patients or donors. SUMMARY: The efforts of transplant providers and donor centers worldwide allowed patients to receive the transplant needed with assurances that they were receiving the best care available despite the worldwide challenge.

Maintaining an adequate sperm donor pool: modifying the medical criteria for sperm donor selection.

The shortage of donor sperm will increase due to greater access by lesbian couples and single women and due to extra rules imposed on sperm donation. Two steps should be distinguished in donor recruitment: an ethical phase where candidates are self-selecting on the basis of ethical rules, and a medical phase where criteria related to quality and safety of the sperm are imposed. The first phase functions as a bottle neck. Candidate donors who reject the ethical rules will not present themselves for donation in clinics and sperm banks. If the ethical rules remain unchanged, the medical rules that apply after the bottle neck should become less stringent if a sufficient number of donors are to be maintained. Lowering the sperm quality standards will lead to more IVF. Although this is regrettable, it will become unavoidable if the scarcity of donors increases.

Hypothermic Oxygenated Machine Perfusion Reduces Early Allograft Injury and Improves Post-transplant Outcomes in Extended Criteria Donation Liver Transplantation From Donation After Brain Death: Results From a Multicenter Randomized Controlled Trial (HOPE ECD-DBD).

OBJECTIVE: The aim of this study was to evaluate peak serum alanine aminotransferase (ALT) and postoperative clinical outcomes after hypothermic oxygenated machine perfusion (HOPE) versus static cold storage (SCS) in extended criteria donation (ECD) liver transplantation (LT) from donation after brain death (DBD). BACKGROUND: HOPE might improve outcomes in LT, particularly in high-risk settings such as ECD organs after DBD, but this hypothesis has not yet been tested in a randomized controlled clinical trial (RCT). METHODS: Between September 2017 and September 2020, 46 patients undergoing ECD-DBD LT from four centers were randomly assigned to HOPE (n = 23) or SCS (n = 23). Peak-ALT levels within 7 days following LT constituted the primary endpoint. Secondary endpoints included incidence of postoperative complications [Clavien-Dindo classification (CD), Comprehensive Complication Index (CCI)], length of intensive care- (ICU) and hospital-stay, and incidence of early allograft dysfunction (EAD). RESULTS: Demographics were equally distributed between both groups [donor age: 72 (IQR: 59-78) years, recipient age: 62 (IQR: 55-65) years, labMELD: 15 (IQR: 9-25), 38 male and 8 female recipients]. HOPE resulted in a 47% decrease in serum peak ALT [418 (IQR: 221-828) vs 796 (IQR: 477-1195) IU/L, P = 0.030], a significant reduction in 90-day complications [44% vs 74% CD grade ≥3, P = 0.036; 32 (IQR: 12-56) vs 52 (IQR: 35-98) CCI, P = 0.021], and shorter ICU- and hospital-stays [5 (IQR: 4-8) vs 8 (IQR: 5-18) days, P = 0.045; 20 (IQR: 16-27) vs 36 (IQR: 23-62) days, P = 0.002] compared to SCS. A trend toward reduced EAD was observed for HOPE (17% vs 35%; P = 0.314). CONCLUSION: This multicenter RCT demonstrates that HOPE, in comparison to SCS, significantly reduces early allograft injury and improves post-transplant outcomes in ECD-DBD liver transplantation.

Recommendations for Donor and Recipient Selection and Risk Prediction: Working Group Report From the ILTS Consensus Conference in DCD Liver Transplantation.

Although the utilization of donation after circulatory death donors (DCDs) for liver transplantation (LT) has increased steadily, much controversy remains, and no common acceptance criteria exist with regard to donor and recipient risk factors and prediction models. A consensus conference was organized by International Liver Transplantation Society on January 31, 2020, in Venice, Italy, to review the current clinical practice worldwide regarding DCD-LT and to develop internationally accepted guidelines. The format of the conference was based on the grade system. International experts in this field were allocated to 6 working groups and prepared evidence-based recommendations to answer-specific questions considering the currently available literature. Working group members and conference attendees served as jury to edit and confirm the final recommendations presented at the end of the conference by each working group separately. This report presents the final statements and recommendations provided by working group 2, covering the entire spectrum of donor and recipient risk factors and prediction models in DCD-LT.

Deletion of TLR4 reduces apoptosis and improves histology in a murine kidney transplant model.

Acute kidney injury (AKI) after transplantation of human deceased donor kidneys is associated with upregulation of tubular toll like receptor 4 (TLR4), but whether TLR4 is required for AKI is unknown. We hypothesized that TLR4 knockout mice (TLR4KO) subjected to cold ischemia followed by kidney transplant (CI + Txp) would be protected from AKI. C57Bl/6J wild type or TLR4KO kidneys were subjected to CI + Txp into wild type recipients. Tubular cell apoptosis, tubular injury and cast formation were significantly improved in recipients of TLR4KO kidneys. TLR4KO kidneys also demonstrated significantly decreased expression of the effector caspase 8. Brush border injury scores and serum creatinine were not different in recipients of TLR4KO versus wild type kidneys. Phosphorylated RIP3 and MLKL through which TLR4 signals programmed necrosis were expressed in both recipient groups. In addition, TNF-α and TNFR1 expression were significantly increased in recipient serum and TLR4KO kidneys respectively after CI + Txp, suggesting continued activation of programmed necrosis despite TLR4 deletion. Our results suggest that TLR4 deletion decreases apoptosis via inhibition of the death receptor pathway and decreases tubular injury and cast formation.