Descriptive study of organ donation and hanging in Australia and New Zealand between 2006 and 2015

INTRODUCTION: The annual incidence of hanging in Australia & New Zealand had increased in the past decade, with an increasing number of such patients appearing to become organ donors. The rates of organ donation following death due to hanging is unknown and the characteristics of this cohort of donors have not been previously described. METHODS: The Australia and New Zealand Organ Donor (ANZOD) registry donor data (2006 - 2015), was analysed, to describe the cohort of donors following hanging, in comparison to other donors. RESULTS: During the study period, both the number and proportion of donors due to hanging have increased between 2006 - 2015. The probability that a victim of hanging would become an organ donor progressively increased from 0.5% to 3%. Compared to other donor groups, the donor population due to hanging is younger (median age 30 years Vs. 50 years), with less co-morbidities, but a higher incidence of smoking. There is no significant difference in the proportion who indicated a prior intent to donate between post-hanging donors (34%) and other donors (38%). A higher proportion of donors post hanging donated via the Donation after circulatory death (DCD) pathway (36.28%) compared to donors with other causes of death (24.2%). Patients in the post hanging cohort donated an average of 4.19 organs, compared to 3.62 organs in the other donor cohort. CONCLUSIONS: It is expected that this retrospective analysis will better inform clinical decision making surrounding organ donation, including consenting approaches while providing care to the patients and families in this challenging group with a high organ donation potential, as demonstrated in this study. Further investigation is required to determine which aspects of health care influence the donation rates in victims of hanging and the outcomes from transplanted organs

Comparison of cause of death between ANZDATA and the Australian national death index.

Aim: The aim of the present study was to understand the differences in how cause of death for patients receiving renal replacement therapy in Australia is recorded in The Australian and New Zealand Dialysis and Transplant Registry (ANZDATA) compared to the National Death Index (NDI). Methods: Data linkage was performed between ANZDATA and NDI for all deaths in the period 1980-2013. Cause of death was classified according to ICD-10 chapter. Overall and chapter specific agreement were assessed using the Kappa statistic. Descriptive analysis was used to explore differences where there was disagreement on primary cause of death. Results: The analysis cohort included 28 675 patients. Ninety five percent of ANZDATA reported deaths fell within +/- 3 days of the date recorded by NDI. Circulatory death was the most common cause of death in both databases (ANZDATA 48%, NDI 32%). Overall agreement at ICD chapter level of primary cause was poor (36%, kappa 0.22). Agreement was best for malignancy (kappa 0.71). When there was disagreement on primary cause of death these were most commonly coded as genitourinary (35%) and endocrine (25.0%) in NDI, and circulatory (39%) and withdrawal (24%) in ANZDATA. Sixty-nine percent of patients had a renal related cause documented as either primary or a contributing cause of death in the NDI. Conclusion: There is poor agreement in primary cause of death between ANZDATA and NDI which is in part explained by the absence of diabetes and renal failure as causes of death in ANZDATA and the absence of 'withdrawal' in NDI. These differences should be appreciated when interpreting epidemiological data on cause of death in the Australian end stage kidney disease population

Characteristics of Organ Donors Who Died From Suicide by Hanging in Australia and New Zealand: A Retrospective Study

Background and objective: The annual incidence of suicide by hanging in Australia and New Zealand has increased in the past decade, and a significant number of these individuals are becoming organ donors. The rates of organ donation following deaths from hanging is unknown and the characteristics of this cohort of donors have not been described in the literature. In light of this, we aimed to examine the trends in organ donation from individuals who had died from hanging, based on the solid organ donor data from the Australia and New Zealand Organ Donation (ANZOD) Registry. Methods: We conducted a retrospective study that analyzed the ANZOD Registry donor data (2006-2015) to describe the characteristics of solid organ donors who had died by hanging (post-hanging group); these characteristics were compared to those of individuals who died by all other causes (non-hanging group). Results: During the study period, the number and proportion of donors who died by suicide from hanging increased. Of the 4,024 consented organ donors, 226 had died by hanging and 3,798 had died from other causes. The probability that an individual who died by hanging would become an organ donor increased from 0.5 to 3%. Compared to donors who died by all other causes, post-hanging donors were younger (median age of 30 vs. 50 years), with fewer comorbidities, and a higher incidence of smoking. There was no significant difference in the proportion of those who indicated a prior intent to donate organs between post-hanging (34%) and non-hanging donors (38%). A higher proportion of post-hanging donors donated via the donation after the circulatory death pathway (36.3%) than non-hanging donors (24.2%). Individuals in the post-hanging cohort donated an average of 4.19 organs compared to 3.62 in the non-hanging cohort. Conclusion: We believe the findings of this retrospective analysis will help inform clinical decision-making regarding organ donation, including the best approaches to obtaining donation consent. Our findings will help physicians provide care to patients and to families of individuals in this challenging group, where organ donation potential is high. Further investigations are required to determine which aspects of healthcare influence the donation rates in individuals who have died by hanging and the outcomes related to transplanted organs

Enhanced Interleukin (IL)-13 Responses in Mice Lacking IL-13 Receptor α 2

Interleukin (IL)-13 has recently been shown to play important and unique roles in asthma, parasite immunity, and tumor recurrence. At least two distinct receptor components, IL-4 receptor (R)α and IL-13Rα1, mediate the diverse actions of IL-13. We have recently described an additional high affinity receptor for IL-13, IL-13Rα2, whose function in IL-13 signaling is unknown. To better appreciate the functional importance of IL-13Rα2, mice deficient in IL-13Rα2 were generated by gene targeting. Serum immunoglobulin E levels were increased in IL-13Rα2−/− mice despite the fact that serum IL-13 was absent and immune interferon γ production increased compared with wild-type mice. IL-13Rα2–deficient mice display increased bone marrow macrophage progenitor frequency and decreased tissue macrophage nitric oxide and IL-12 production in response to lipopolysaccharide. These results are consistent with a phenotype of enhanced IL-13 responsiveness and demonstrate a role for endogenous IL-13 and IL-13Rα2 in regulating immune responses in wild-type mice

Redesigning deceased donor kidney transplant allocation in Australia

© 2020 Matthew Peter SypekKidney transplantation is a life changing event for a person living with end stage kidney disease and the allocation of deceased donor kidneys can have profound impacts on who has access to this treatment, the benefit that is derived from the gift of donation and the long term outcomes for the individual receiving the organ. The system that determines the allocation of deceased donor kidneys comprises a number of interconnected processes and must address a range of competing priorities. This thesis presents a series of related studies that provide evidence on the current state of deceased donor kidney allocation and demonstrate the feasibility and effectiveness of a novel framework for redesigning organ allocation protocols in Australia. In order to better understand the context in which allocation occurs, Chapters 3 and 4 address key knowledge gaps in the Australian deceased donor kidney transplant system, reporting on the predictors of access to kidney transplant waitlisting in Australia, highlighting the disadvantage experienced by key populations, and exploring the causes of a recent increase in kidney non-utilisation. Chapter 5, 6 and 7 analyse the impacts of previous changes to the allocation system, assessing their effectiveness, unintended consequences and highlighting key areas in which further policy intervention is required. The study reported in chapter 5 demonstrates that the reporting of the Kidney Donor Performance Index (KDPI) with organ offers in Australia was associated with changes in acceptance behaviour but not an increase in non-utilisation and provide insights into how donor risk indices might be incorporated into future allocating algorithms. Analysis of the impact of the introduction of calculated panel reactive antibody (cPRA) to define sensitization for kidney transplant candidates, described in chapter 6, reveals the scale of disadvantage experienced by very highly sensitized patients and the ineffectiveness of the current allocation system in addressing this, adding urgency to the call for policy change to address this. Further evidence to support change is reported in chapter 7, in an analysis of the effectiveness of paediatric bonuses in the Australian deceased donor kidney allocation system. This shows that whilst paediatric candidates are achieving rapid access to high quality organs, under current rules children are not receiving kidneys with optimal immunological matching. Chapter 8 explores the association between HLA epitope based matching and clinical outcomes in the paediatric population to investigate whether this may have potential as a novel approach to reducing immunological risk through optimised allocation. Addressing the broader question of what the allocation system should be trying to achieve, results of a best worse scaling choice experiment presented in Chapter 9 show key differences in the principles prioritized by healthcare professionals when compared to the general community. The final chapter of the thesis reports the development, validation and implementation of a platform to simulate deceased donor kidney allocation in Australia. In working closely with the national Renal Transplant Allocation Committee (RTAC), this study not only provided proof of concept for the value of simulation in organ allocation policy development in Australia but produced direct and tangible improvements in the policy that will be implemented. In taking a holistic approach to the process of redesigning deceased donor kidney allocation this work reports several novel findings that have had a direct impact on policy development and lays the foundations for an ongoing framework of evidence-based design for deceased donor kidney allocation in Australia

ABO blood group relationships to kidney transplant recipient and graft outcomes

Introduction: Certain ABO blood types have been linked to cardiovascular disease, infection and cancers. The effect of recipient ABO blood group on patient and graft survival has not been studied in ABO-matched kidney transplantation. This study aims to determine the association between kidney transplant recipient ABO blood groups with patient and graft survival in Australian and New Zealand. Methods: All Australian and New Zealand transplant recipients who received ABO-compatible primary kidney transplants between 1995–2016 were analysed using a de-identified dataset from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Primary analysis was undertaken of recipient ABO blood group O versus non-O blood groups. The primary outcome was patient survival post kidney transplantation and the secondary outcome was death censored graft survival. Recipient age at first transplant, gender, ethnicity, body mass index, smoking status, vascular disease, presence of diabetes mellitus, chronic lung disease, primary kidney disease, donor source, donor age and gender, and era of transplants were included in the multivariate model as confounders. Results and conclusions: On analysis of 15,523 kidney transplant recipients, blood group O was not associated with patient survival (hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.89–1.04) nor death censored graft survival (HR 0.97, 95% CI 0.89–1.05) compared to non-blood group O recipients. Competing risks analyses showed an increased risk of cancer-related mortality in blood group O recipients on univariate analyses (HR 1.18, 95% CI 1.01–1.37) however, this became insignificant on multivariate analyses. On secondary analyses, recipient blood group AB (4.11% participants) was associated with inferior death censored graft survival compared to those with blood group O (HR 1.24, 95% CI 1.02–1.50). Although recipient ABO blood groups were not associated with patient nor graft survival, differences in cause-specific mortality between individual blood groups cannot be excluded based on current analyses

Donor kidney quality and transplant outcome:An economic evaluation of contemporary practice

Objectives: The study had two main aims. First, we assessed the cost-effectiveness of transplanting deceased donor kidneys of differing quality levels based on the Kidney Donor Profile Index (KDPI). Second, we assessed the cost-effectiveness of remaining on the waiting list until a high-quality kidney becomes available compared to transplanting a lower-quality kidney. Methods: A decision analytic model to estimate cost-effectiveness was developed using a Markov process. Separate models were developed for 4 separate KDPI bands, with higher values indicating lower quality. Models were simulated in 1-year cycles for a 20-year time horizon, with transitions through distinct health states relevant to the kidney recipient from the healthcare payer's perspective. Weibull regression was used to calculate the time-dependent transition probabilities in the base analysis. The impact uncertainty arising in model parameters was included by probabilistic sensitivity analysis using the Monte Carlo simulation method. Willingness to pay was considered as Australian $28 000. Results: Transplanting a kidney of any quality is cost-effective compared to remaining on a waitlist. Transplanting a lower KDPI kidney is cost-effective compared to a higher KDPI kidney. Transplanting lower KDPI kidneys to younger patients and higher KDPI kidneys to older patients is also cost-effective. Depending on dialysis in hopes of receiving a lower KDPI kidney is not a cost-effective strategy for any age group. Conclusion: Efforts should be made by the health systems to reduce the discard rates of low-quality kidneys with the view of increasing the transplant rates.</p

Deceased donor kidney allocation: an economic evaluation of contemporary longevity matching practices

Matching survival of a donor kidney with that of the recipient (longevity matching), is used in some kidney allocation systems to maximize graft-life years. It is not part of the allocation algorithm for Australia. Given the growing evidence of survival benefit due to longevity matching based allocation algorithms, development of a similar kidney allocation system for Australia is currently underway. The aim of this research is to estimate the impact that changes to costs and health outcomes arising from 'longevity matching' on the Australian healthcare system.A decision analytic model to estimate cost-effectiveness was developed using a Markov process. Four plausible competing allocation options were compared to the current kidney allocation practice. Models were simulated in one-year cycles for a 20-year time horizon, with transitions through distinct health states relevant to the kidney recipient. Willingness to pay was considered as AUD 28000.Base case analysis indicated that allocating the worst 20% of Kidney Donor Risk Index (KDRI) donor kidneys to the worst 20% of estimated post-transplant survival (EPTS) recipients (option 2) and allocating the oldest 25% of donor kidneys to the oldest 25% of recipients are both cost saving and more effective compared to the current Australian allocation practice. Option 2, returned the lowest costs, greatest health benefits and largest gain to net monetary benefits (NMB). Allocating the best 20% of KDRI donor kidneys to the best 20% of EPTS recipients had the lowest expected incremental NMB.Of the four longevity-based kidney allocation practices considered, transplanting the lowest quality kidneys to the worst kidney recipients (option 2), was estimated to return the best value for money for the Australian health system

Development and validation of a risk index to predict kidney graft survival: the kidney transplant risk index

Background: Kidney graft failure risk prediction models assist evidence-based medical decision-making in clinical practice. Our objective was to develop and validate statistical and machine learning predictive models to predict death-censored graft failure following deceased donor kidney transplant, using time-to-event (survival) data in a large national dataset from Australia.Methods: Data included donor and recipient characteristics (n = 98) of 7,365 deceased donor transplants from January 1st, 2007 to December 31st, 2017 conducted in Australia. Seven variable selection methods were used to identify the most important independent variables included in the model. Predictive models were developed using: survival tree, random survival forest, survival support vector machine and Cox proportional regression. The models were trained using 70% of the data and validated using the rest of the data (30%). The model with best discriminatory power, assessed using concordance index (C-index) was chosen as the best model.Results: Two models, developed using cox regression and random survival forest, had the highest C-index (0.67) in discriminating death-censored graft failure. The best fitting Cox model used seven independent variables and showed moderate level of prediction accuracy (calibration).Conclusion: This index displays sufficient robustness to be used in pre-transplant decision making and may perform better than currently available tools