Catherine Boffa

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.

Past, Present, and Future of Dynamic Kidney and Liver Preservation and Resuscitation

The increased demand for organs has led to the increased usage of “higher risk” kidney and liver grafts. These grafts from donation after circulatory death or expanded criteria donors are more susceptible to preservation injury and have a higher risk of unfavorable outcomes. Dynamic, instead of static, preservation could allow for organ optimization, offering a platform for viability assessment, active organ repair and resuscitation. Ex situ machine perfusion and in situ regional perfusion in the donor are emerging as potential tools to preserve and resuscitate vulnerable grafts. Preclinical findings have ignited clinical organ preservation research that investigates dynamic preservation, its various modes (continuous, preimplantation) and temperatures (hypo‐, sub, or normothermic). This review outlines the current status of dynamic preservation of kidney and liver grafts and describes ongoing research and emerging clinical trials.

Utilization of organs from donors after circulatory death for vascularized pancreas and islet of Langerhans transplantation: recommendations from an expert group

Donation after circulatory death (DCD) donors are increasingly being used as a source of pancreas allografts for vascularized organ and islet transplantation. We provide practice guidelines aiming to increase DCD pancreas utilization. We review risk assessment and donor selection criteria. We report suggested factors in donor and recipient clinical management and provide an overview of the activities and outcomes of vascularized pancreas and islet transplantation.

Transplantation of kidneys from donors with acute kidney injury: Friend or foe?

The gap between supply and demand in kidney transplantation has led to increased use of marginal kidneys; however, kidneys with acute kidney injury are often declined/discarded. To determine whether this policy is justified, we analyzed outcomes of donor kidneys with acute kidney injury (AKI) in a large UK cohort. A retrospective analysis of the UK Transplant Registry evaluated deceased donors between 2003 and 2013. Donors were classified as no AKI, or AKI stage 1–3 according to Acute Kidney Injury Network (AKIN) criteria. Relationship of AKI with delayed graft function/primary nonfunction (DGF/PNF), estimated glomerular filtration rate (eGFR), and graft‐survival at 90 days and 1 year was analyzed. There were 11 219 kidneys (1869 [17%] with AKI) included. Graft failure at 1 year is greater for donors with AKI than for those without (graft survival 89% vs. 91%, p = 0.02; odds ratio (OR) 1.20 [95% confidence interval (CI): 1.03–1.41]). DGF rates increase with donor AKI stage (p < 0.005), and PNF rates are significantly higher for AKIN stage 3 kidneys (9% vs. 4%, p = 0.04) Analysis of association between AKI and recipient eGFR suggests a risk of inferior eGFR with AKI versus no AKI (p < 0.005; OR 1.25 [95% CI: 1.08–1.31]). We report a small reduction in 1‐year graft‐survival of kidneys from donors with AKI. We conclude that AKI stage 1 or 2 kidneys should be used; however, caution is advised for AKI stage 3 donors.

Ethical, legal, and societal issues and recommendations for controlled and uncontrolled DCD

This report deals with organ retrieval procedures in both controlled and uncontrolled DCD, looking at the ethical, legal, and psychosocial aspects during the different phases of the process. A recently published report by the UK Donation Ethics Committee (UKDEC) has served as an important reference document to outline the steps in the controlled DCD patient–donor pathway (Academy of Medical Royal Colleges. UK Donation Ethics Committee. An ethical framework for controlled donation after circulatory death. December 2011). For uncontrolled DCD, the UKDEC pathway description was adapted. At the 6th International Conference in Organ Donation held in Paris in 2013, an established expert European Working Group reviewed the UKDEC reports, which were then considered along with the available published literature. Along this pathway, the crucial ethical, legal, and psychosocial aspects have been flagged, and relevant recommendations have been formulated based on a consensus of the working group.

In-hospital logistics: what are the key aspects for succeeding in each of the steps of the process of controlled donation after circulatory death?

Donation after circulatory death (DCD) donors are becoming an increasingly important population of organ donors in Europe and worldwide. We report the state of the art regarding controlled DCD donation describing the organizational and technical aspects of establishing a controlled DCD programme and provide recommendations regarding the introduction and development of this type of programme.

Efficacy and Quality of Flush-Out Prior to Cold Storage of Liver and Kidney in Donation after Circulatory Death

Background and Aims There is a general perception that viscous solutions reduce the rate at which blood is washed out of organs during the cold flush during procurement, inhibit efficient cool-down, and prohibit optimal cortical perfusion of donor organs. Actual data on this topic are scarce but opinions are strong. To study perfusion characteristics we compared four hypothermic preservation solutions for abdominal organs i.e. UW SCS, HTK, IGL-1 and UW-MPS in a large animal model simulating donation after circulatory death (DCD). Materials and Methods Twenty 70kg female pigs were terminated [UW (6) and HTK (6), IGL-1 (4), UW-MPS (4)] followed by aortic cold flush-out and addition of slush-ice after 40min warm ischaemia. Companies’ instructions for volumes were used. During wash-out at pre-defined time points perfusate samples were obtained for further analysis and to determine viscosity. Organ temperature was measured continuously and cortical perfusion of kidney and liver was recorded using contrast-enhanced ultrasound. Biopsies were taken at start and end for histology and EM, including assessment of wash-out of blood. Results All solutions decreased the temperature of liver and kidney, although no solution reached temperatures lower than 18°C and 15°C resp. No significant difference in end liver temperatures was observed between different solutions (p=0.63), however end temperatures of kidneys were significantly different when comparing UW to HTK (15.1°C vs 20.3°C) (p=0.04). Cortical perfusion of livers was equally good between solutions (p=0.28), while in kidneys UW and IGL-1 penetrated better compared to HTK (p=0.02 and 0.03, resp.). No significant differences in histology or EM were seen in kidneys at the beginning or the end of the procedure, reflecting adequate intravascular wash-out, irrespective of viscosity. Discussion This study contradicts a popular perception and provides evidence that increased viscosity of a preservation solution does not negatively affect cooling and quality of organ perfusion. In fact, we found that UW SCS may be better at flushing out blood and cooling DCD kidneys. This study also provides interesting physiological data about the interaction between cold flush-out solutions and kidney and liver tissue at time of retrieval and start of preservation. Conclusion A higher viscosity in a preservation solution does not negatively affect cooling during flush-out at time of retrieval and does not have any detrimental effect on the quality of organ perfusion and preservation.

Transplantation of Kidneys From Donors With Acute Kidney Injury: Friend or Foe?

Introduction The widening gap between supply and demand in kidney transplantation has lead to the increased use of kidneys from marginal donors, including those with acute kidney injury (AKI). Despite the organ shortage, donor kidneys with AKI are often declined or discarded. To determine if this policy is justified we have analysed outcomes of AKI in a large UK cohort. Methods In a retrospective analysis of the UK transplant registry, adult deceased donors between 2003-2008 were evaluated. Donors were classified as no AKI, or AKI stage 1, 2 or 3 according to the AKIN criteria defined by change in creatinine between admission and donation. Relationship of AKI with DGF/PNF, eGFR and graft survival (GS) at 90d and 1y using risk adjusted Cox regression analysis. Results 11,244 kidneys were included in the analysis. 35% of AKI kidneys were not accepted or transplanted. There is evidence that the chance of graft failure (GF) at 1y is greater for donors with AKI than for those without (GS 89% v 91%, p=0.02; OR 1.20 (95% CI: 1.03-1.41)). The odds of DGF and PNF increase with donor AKI stage (p<0.005, p=0.04 resp). Analysis of association between donor AKI and recipient eGFR suggests risk of inferior eGFR with increasing AKI stage versus no AKI (p<0.005; OR 1.25 (95% CI: 1.08-1.31)). Discussion This study shows that a significant number of donor kidneys with AKI are discarded. We report a small but significant reduction of 2% in 1y GS of kidneys from donors with AKI. The 20% increased risk of graft failure due to AKI in the donor is similar to the 17% increased risk of graft failure associated with dialysis vintage of 6 months when compared to pre-emptive transplantation, and is significantly lower than the 37% and 55% increased risk of graft failure when dialysing for longer than 1 or 2 years prior to kidney transplantation (Meier-Kriesche, 2005). In this analysis, over 1500 recipients received a donor kidney with AKI and still had a functioning graft at 1y. We conclude that donor kidneys with AKI stage 1 or 2 should not be discarded as they give comparable outcomes; due to its small sample size we cannot but advise to be cautious for AKI stage 3 donors.

The Impact of Duration of Brain Death on Outcomes in Abdominal Organ Transplantation: Rush and Retrieve or Relax and Repair 2017? A Retrospective UK Transplant Registry Analysis

Background Brain death (BD) induces a profound inflammatory response affecting the quality and function of donor organs. Longer BD duration increases injury in donor organs, but up-regulation of defence mechanisms also occurs, initiating regeneration and repair. This poses the question what is better for the graft-to-be: retrieval of the organs as-soon-as-possible or wait and optimise in-situ repair? Methods A retrospective analysis of the UK transplant registry evaluated donors after brain death DBD donors during 2008-2012. In 1881 donors the relationship between BD duration and function or graft-survival at 1 and 3-years was analysed using multivariate and Cox regression analyses of 2815 kidneys, 1555 livers and 588 pancreata. Results Longer BD duration did not have a detrimental association with liver transplant survival (p = 0.89, 1 yr survival), whilst in fact prolonged BD duration was associated with increased transplant survival following first kidney-only transplantation (p = 0.02, 1 yr survival) for prolonged cold ischaemic time (18-24 hours) and following pancreas transplantation (p < 0.0001, 1 yr survival) in recent years. Although delayed graft function was more common in kidney transplants as the duration of BD increased (p < 0.0001), there was no association with primary non-function (p = 0.62). Longer BD duration had no detrimental association with graft function at 1 year when the donor was 30 years or older and was associated with increased graft function for donors aged 30 to 40 years (p = 0.01). Discussion This demonstrates that prolonged BD is not detrimental to outcomes in abdominal organ transplantation. This finding supports that time for donor management may be effectively used to adequately optimise donor organs. This analysis renounces the need for a ‘Rush and Retrieve’ policy and suggests that the DBD environment may be less ‘hostile’ than is perceived, allowing sufficient time to support repair through targeted intervention prior to organ retrieval.

Should Pulsatile Preservation Be the Gold Standard in Kidney Transplantation

In recent years, dramatic improvements in kidney transplantation, together with a rising incidence of diseases such as diabetes, have led to an increasing demand for deceased donor kidneys for transplantation. Hence, it has been necessary to expand the kidney donor pool by using organs once considered unsuitable for transplantation. These higher risk kidneys are typically from older donors with additional comorbidities and are more susceptible to injury. Therefore, the transplant community has been focusing efforts in trying to improve the outcomes of these high-risk organs. Preservation by pulsatile machine perfusion has been associated with decreased risk of delayed graft function and renoprotective effects on deceased donor kidneys. The aim of this review is to provide an overview of the principles of this preservation technique and to review the evidence regarding its usage for deceased donor kidneys compared to standard static cold storage.