Case report: Heart retransplant from a donor after circulatory death and extended transport period with normothermic perfusion.

A 55-year-old man with end-stage heart failure, who had an orthotopic heart transplant 21 years prior, underwent heart retransplantation using a heart from a donor with circulatory death in a distant location and an extended transport period with normothermic ex vivo perfusion. Owing to the persistent and worsening shortage of donor hearts, this case illustrates that expanding the donor acceptance criteria to include more distant donor locations and enrolling recipients with extended criteria (e.g., heart retransplantation) is feasible.

Impact of suboptimal donor to suboptimal recipient kidney transplant on delayed graft function and outcome.

Introduction: The demographics of donor and recipient candidates for kidney transplantation (KT) have substantially changed. Recipients tend to be older and polymorbid and KT to suboptimal recipients is associated with delayed graft function (DGF), prolonged hospitalization, inferior long-term allograft function, and poorer patient survival. In parallel, donors are also older, suffer from several comorbidities, and donations coming from circulatory death (DCD) predominate, which in turn leads to early and late complications. However, it is unclear how donor and recipient risk factors interact. Methods: In this retrospective cohort study, we assess the impact of a KT from suboptimal donors to suboptimal recipients. We focused on: 1) DGF; 2) hospital stay and number of dialysis days after KT and 3) allograft function at 12 months. Results and discussion: Among the 369 KT included, the overall DGF rate was 25% (n = 92) and median time from reperfusion to DGF resolution was 7.8 days (IQR: 3.0-13.8 days). Overall, patients received four dialysis sessions (IQR: 2-8). The combination of pre-KT anuria (<200 ml/24 h, 32%) and DCD procurement (14%) was significantly associated with DGF, length of hospital stay, and severe perioperative complications, predominantly in recipients 50 years and older.

Single Center Experience with Incidence, Impact and Predictors of Biliary Complications in Donation After Circulatory Death Liver Transplantation.

Introduction: Utilizing allografts from donors after cardiac death (DCD) has improved organ availability, and DCD livers comprise a growing proportion of transplantations. However, it has been suggested that DCD transplantations have worse outcomes. Research Questions: We aimed to characterize outcomes in a large cohort of DCD transplantations, identify trends in outcomes over time, and identify factors associated with the development of biliary complications. Design: We conducted an observational retrospective cohort study of patients receiving DCD liver allografts within a large academic teaching hospital with a high transplantation volume. Consecutive patients who underwent Type III DCD liver transplantation from 2006-2016 were included in our cohort. Re-transplantations and multi-organ transplant recipients were excluded. Results: Ninety-six type III DCD transplantations occurred between 2006-2016. We report a 1one-year patient survival of 90.6% (87) and a 5five-year patient survival of 69.8% (67). Twenty-nine (30.2%) patients experienced any biliary complication in the first year following discharge, with 17 (17.7%) experiencing ischemic cholangiopathy. Five-year patient (P = 0.04) and graft (P = 0.005) survival improved over time. Post-operative biliary complications experienced during index admission and prior to discharge were found to be associated with the development of biliary complications (P = 0.005) and ischemic cholangiopathy (P = 0.01) following discharge. Conclusion: Our data suggested that outcomes using DCD allografts have improved, however biliary complications remain a significant issue in DCD transplantation. Patients who experienced post-operative biliary complications during index admission may require more frequent screening to allow the initiation of earlier treatment for biliary complications.

Early Hypertransaminasemia after Kidney Transplantation: Significance and Evolution According to Donor Type.

Early hypertransaminasemia after kidney transplantation (KT) is frequent. It has been associated with the crosstalk produced between the liver and the kidney in ischemia-reperfusion situations. However, the influence of the donor type has not been evaluated. We present a retrospective study analyzing the increase in serum aspartate aminotransferase/alanine aminotransferase (AST/ALT) during the first three months post-KT in 151 recipients who received thymoglobulin as induction therapy, either from brain-death donors (DBD, n = 75), controlled circulatory death donors (cDCD, n = 33), or uncontrolled DCD (uDCD, n = 43). Eighty-five KT recipients from DBD who received basiliximab were included as controls. From KT recipients who received thymoglobulin, 33.6/43.4% presented with an increase in AST/ALT at 72 h post-KT, respectively. Regarding donor type, the percentage of recipients who experienced 72 h post-KT hypertransaminasemia was higher in uDCD group (65.1/83.7% vs. 20.3/26% in DBD and 20.7/27.6% in cDCD, p < 0.001). Within the control group, 9.4/12.9% of patients presented with AST/ALT elevation. One month after transplant, AST/ALT values returned to baseline in all groups. The multivariate analysis showed that uDCD recipients had 6- to 12-fold higher risk of developing early post-KT hypertransaminasemia. Early post-KT hypertransaminasemia is a frequent and transient event related to the kidney donor type, being more frequent in uDCD recipients.

The efficacy of HBOC-201 in ex situ gradual rewarming kidney perfusion in a rat model.

Gradual rewarming from hypothermic to normothermic is a novel perfusion modality with superior outcome to sudden rewarming to normothermic. However, the identification of an oxygen carrier that could function at a temperature range from 4 to 7°C or whether it is necessary to use oxygen carrier during kidney rewarming, remains unresolved. This study was designed to test the use of a hemoglobin-based oxygen carrier (HBOC) during gradual kidney rewarming as an alternative to simple dissolved oxygen. In this study, 10 rat kidneys were randomly divided into the control and the HBOC group. In the control group, no oxygen carrier was used during rewarming perfusion and the perfusion solution was oxygenated only by applying diffused carbogen flow. The protocol mimicked a donor after circulatory death (DCD) kidney transplantation, where after 30 minutes warm ischemia and 120 minutes cold storage in University of Wisconsin solution, the DCD kidneys underwent gradual rewarming from 10 to 37°C during 90 minutes with or without HBOC. This was followed by 30 minutes of warm ischemia in room temperature to mimic the anastomosis time and 120 minutes of reperfusion at 37°C to mimic the early post-transplant state of the graft. The HBOC group demonstrated superior kidney function which was highlighted by higher ultrafiltrate production, better glomerular filtration rate and improved sodium reabsorption. There was no significant difference between the 2 groups regarding the hemodynamics, tissue injury, and adenosine triphosphate levels. In conclusion, this study suggests better renal function recovery in DCD kidneys after rewarming with HBOC compared to rewarming without an oxygen carrier.

Hypothermic Machine Perfusion Results in a Marginal Kidney Transplant Programme.

BACKGROUND: Hypothermic machine perfusion (HMP) of deceased donor kidneys is associated with a better outcome than static cold storage, predominantly in marginal donors. Nevertheless, there is little evidence supporting whether graft centre of origin and donor category impact HMP results. OBJECTIVE: To identify factors impacting HMP in transplantation from marginal donors. DESIGN, SETTING, AND PARTICIPANTS: Analysis of prospectively collected cohort data of expanded criteria donor (ECD) and donor after circulatory death (DCD) categories II and III was performed. A total of 214 adult recipients of first kidney transplantation with complete data and a minimum of 6-mo follow-up were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Delayed graft function (DGF) was defined as the lack of decrease in creatinine level in the first 48h. Graft loss was defined as return to dialysis or creatinine clearance <15ml/min/1.73m2. Univariate and multivariate logistic regression analyses for DGF were constructed to identify independent risk factors. Recipient and graft survival (GS) analyses were conducted by Kaplan-Meier, and univariate and multivariate Cox regression analyses. RESULTS AND LIMITATION: DGF occurred in 32.8% of imported and 20.5% of local grafts (p=0.059). Only donor category (DCD; odds ratio [OR]: 6.6, p=0.008) and haemodialysis (OR: 3.5, p=0.002) were significantly associated with DGF development. The 1-yr GS rate was 92.5% in the local donor group and 84.3% in the imported donor group (p=0.050). Multivariate analysis by Cox proportional hazards model identified only donor category (hazard ratio [HR] 10.99, p=0.001) and donor age (HR 1.07, p=0.005) as predictive variables for GS. The small sample size of the DCD group diminished the statistical power and did not permit a subgroup analysis to determine the impact of specific DCD category on HMP results. CONCLUSIONS: DCD donor category, but not donor centre of origin, impacted DGF development and GS in the HMP of deceased donor kidneys. PATIENT SUMMARY: Currently, the number of donors is insufficient to meet the demand for renal grafts. Expanded criteria for donation after brain death and donation after circulatory death (DCD) programmes have been developed as strategies to minimise this problem. Hypothermic machine perfusion has previously demonstrated its usefulness in expanded criteria donation and DCD preservation. DCD type and donor age increase the risk of graft loss.

Machine perfusion of thoracic organs.

This article summarizes recent knowledge and clinical advances in machine perfusion (MP) of thoracic organs. MP of thoracic organs has gained much attention during the last decade. Clinical studies are investigating the role of MP to preserve, resuscitate, and assess heart and lungs prior to transplantation. Currently, MP of the cardiac allograft is essential in all type DCD heart transplantation while MP of the pulmonary allograft is mandatory in uncontrolled DCD lung transplantation. MP of thoracic organs also offers an exciting platform to further investigate downregulation of the innate and adaptive immunity prior to reperfusion of the allograft in recipients. MP provides a promising technology that allows pre-transplant preservation, resuscitation, assessment, repair, and conditioning of cardiac and pulmonary allografts outside the body in a near physiologic state prior to planned transplantation. Results of ongoing clinical trials are awaited to estimate the true clinical value of this new technology in advancing the field of heart and lung transplantation by increasing the total number and the quality of available organs and by further improving recipient early and long-term outcome.

Heart transplantation after the circulatory death; The ethical dilemma.

Donors after brain death (DBD) have been the major source of organ donation due to good perfusion of the organs. However, owing to the mismatch in demand and supply of the organ donors and recipients, donors after circulatory death (DCDDs) has increased recently all over the world. Kidneys, liver, and lungs are being used for transplantation from DCDDs. Recently, heart transplantation from DCDDs has been started, which is under the firestorm of scrutiny by the ethicists. The ethical dilemma revolves around the question whether the donors are actually dead when they are declared dead by cardiocirculatory death criteria for organ procurement. The subsequent literature review addresses all the perspectives by differentiating between the donation methods known as DBDs and DCDDs, explaining the implications of the dead-donor rule on the organ donation pool, and categorizing the determinants of death leading to separation of the arguments under the two methods of donations.

New classification of donation after circulatory death donors definitions and terminology.

In the face of a crisis in organ donation, the transplant community are increasingly utilizing donation after circulatory death (DCD) donors. Over the last 10 years, with the increasing usage of DCD donors, we have seen the introduction in a number of new terms and definitions. We report the results of the 6th International Conference in Organ Donation held in Paris in 2013 and report a consensus agreement of an established expert European Working Group on the definitions and terminology regarding DCD donation, including refinement of the Maastricht definitions. This document forms part of a special series where recommendations are presented for uncontrolled and controlled DCD donation and organ specific guidelines for kidney, pancreas, liver and lung transplantation. An expert panel formed a consensus on definitions and terms aiming to establish consistent usage of terms in DCD donation.

Patient with liver dysfunction while maintained on veno-venous extracorporeal membrane oxygenation should not be overlooked as a potential donor.

This report describes transplantation of liver allograft from a circulatory death donor who was supported by veno-venous extracorporeal membrane oxygenation (ECMO) for 14 days and presented with severely altered liver functions. Successful liver transplant was done in a patient with hepatocellular carcinoma (HCC) in the background of primary sclerosing cholangitis. There was immediate graft function and uneventful recovery with stable graft function at 1-year follow-up. This case illustrates the ability of veno-venous ECMO to resuscitate organs in the presence of severe dysfunction, and perhaps, lessons from this case may be incorporated to optimize the condition of organs rescued from these marginal donors and exemplify the use of ECMO in normothermic regional perfusion in donors after circulatory death.