Publications

AbstractIntroductionWith the growing demand for kidney transplants, kidneys from donors with diabetes mellitus are used more frequently. This raises the concerning possibility that a kidney with early-stage diabetic nephropathy may be transplanted into a recipient who subsequently develops posttransplant dysglycemia; however, it is unclear what impact this will have on graft function and survival. This study investigated graft and patient survival when the donor, recipient, or both have diabetes.MethodsData from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry were used to analyze first-time adult recipients of deceased-donor kidneys between 2003 and 2022. Cox proportional hazards models were used to compare primary outcomes of death-censored graft survival and patient survival across combinations of donor and recipient diabetic status. Secondary outcomes of rejection and estimated glomerular filtration rate (eGFR) over time were analyzed with logistic regression and linear mixed models, respectively.ResultsThe 11,343 recipients included 7377 donor-recipient nondiabetic pairs (D−/R−), 3253 diabetic recipients-nondiabetic donors (D−/R+), 524 nondiabetic recipients-diabetic donors (D+/R−), and 189 both donor and recipient diabetic (D+/R+). Death-censored graft survival was reduced only in the D+/R+ group (adjusted hazard ratio [aHR]: 1.70, 95% confidence interval [CI]: 1.15–2.51, P = 0.008). Diabetic recipients had the poorest survival, particularly in the D+/R+ group (aHR: 1.77, 95% CI: 1.33–2.37, P < 0.001). There was no difference in rejection and only a minor reduction in eGFR for recipients of diabetic donor kidneys.ConclusionThe D+/R+ combination is associated with inferior graft and patient survival and should be considered cautiously. This study supports continued use of diabetic donors with no impact on graft or patient survival in nondiabetic recipients.

Background: An efficient organ donation programme must maximise transplantation following initiation of organ recovery procedures.Methods: We conducted a cohort study of deceased donors in Australia (2014-2021) using Australia and New Zealand Organ Donation Registry data to characterise kidney non-retrieval (post-incision) and non-utilisation (retrieved, not transplanted). Donor characteristics included kidney side (left/right), kidney-only procurement, kidney donor profile index (KDPI), cause of death, resuscitation, donation after circulatory/neurological determination of death (DCDD/DNDD) and donor criteria (standard SCD/extended ECD), year, age, sex, blood group, ethnicity, comorbidities, smoking, BMI, weight, remoteness, occupation and socioeconomic disadvantage. System characteristics included jurisdiction of donor hospital, retrieval team and recipient's hospital.Results: Among 7211 kidneys (3683 donors) accepted for retrieval, 675 (9%) were non-retrieved and 430 (7%) were non-utilised. Crude non-retrieval rates doubled from 5% to 10% between 2014 and 2021 (p = 0.01) while non-utilisation remained around 7% (p = 0.1). After adjustment, non-retrieval was greater among donors with KDPI ≥ 75 (OR: 4.28, 95% CI: 2.08-8.81, p < 0.001), diabetes (OR: 1.74, 95% CI: 1.25-2.43, p = 0.001) and in recent years (annual OR: 1.08, 95% CI: 1.03-1.55, p = 0.002), and lower for ECD DCDD (OR: 0.46, 95% CI: 0.26-0.81, p = 0.01). Non-utilisation was greater for SCD DCDD (OR: 1.90, 95% CI: 1.28-2.82, p < 0.001), blood group AB (OR: 2.05, 95% CI: 1.16-3.64, p = 0.03) and in recent years (annual OR: 1.08, 95% CI: 1.02-1.15, p = 0.01), and lower in Tasmania (OR: 0.28, 95% CI: 0.08-0.97) and Queensland (OR: 0.57, 95% CI: 0.36-0.92, p = 0.03). Documented reasons for non-utilisation lacked transparency but included poor perfusion (17%).Conclusion:Increasing utilisation of higher KDPI kidneys and enhancing perfusion could help maximise kidney transplantation.

Background: Increasing deceased organ donation is a worldwide priority constrained by concerns of inadvertent transmission of cancer or infectious diseases from deceased organ donors. Up to 60% of potential donors referred for consideration for deceased organ donation in Australia do not proceed due to biovigilance concerns.Objective: We aim to describe the impact of accepting or declining potential donors foregone for biovigilance concerns on patient and transplant outcomes.Methods: The MODUS (Maximizing Organ Donor Utility Systemwide) study will use data for patients ever waitlisted for kidney transplantation and all potential donors referred for consideration for deceased organ donation. First, we will use binational data from the Australian and New Zealand Dialysis and Transplant Registry 2010-2020 to describe and evaluate factors impacting the current patient journey on the kidney transplant waitlist, including episodes of suspension and reactivation, time waiting, and whether transplanted. Second, we will quantify the time from offer decline to deceased donor transplantation and the impact of the intersectional disadvantage on the waiting time after decline for patients on the waitlist using flexible parametric survival models. Third, the MODUS study will use an established dataset of outcome data for all candidates for deceased organ donors referred to the New South Wales (NSW) Organ and Tissue Donation Service (OTDS) in 2010-2020 to describe donor referral risk profiles and determine any potential donor gains that could be made through better access to donor information at the time of decision-making, more accurate estimation of the absolute biovigilance risk, and varying of the acceptable biovigilance risk thresholds for accepting donors. Lastly, we will use the estimates derived from the first 3 aims as inputs for health economic models, where, using cohort- and individual patient-level simulations, we will quantify the impact of varying donor referral decisions on health care costs, quality-adjusted survival, the time on the waitlist, and the time to a kidney transplant.Results: Linked health data were received in 2023. Data analysis is ongoing, and results will be disseminated at scientific conferences, published in the scientific media, and published via collaborator networks in 2025.Conclusions: The MODUS study will provide evidence of the individual-level and health service effects of increasing acceptance of deceased donor kidneys that would otherwise be declined due to biovigilance concerns. Specifically, we expect to report our findings on improvements in overall patient survival and quality of life by increasing the number of waitlisted people transplanted from donors with an acceptable biovigilance risk who are currently foregone. We will also report on the cost-effectiveness of a potential "informed biovigilance strategy" versus current practice. In doing so, we will develop evidence to support policy and complex clinical decisions in Australia's organ donor referral process with potential worldwide application.

AbstractDelayed graft function (DGF), is associated with inferior graft outcomes. Whether poor graft function without dialysis, termed slow graft function (SGF), affects outcomes is unclear. We investigated associations between SGF (serum creatinine dropping by less than 30% between days 1 and 2), DGF and graft outcomes by donor type in a cohort of 17,579 Australian and New Zealand kidney transplant recipients from 2001-2021. The primary outcomes were graft survival and death-censored graft survival Compared with immediate graft function, both SGF (Adjusted hazard ratio [aHR] 1.48 (95% CI 1.14-1.91) and DGF [aHR 1.97 (1.42-2.73)] were associated with reduced graft survival in living donor and donation after brain death (DBD) recipients [SGF aHR 1.13 (1.01-1.27); DGF aHR 1.37 (1.24-1.51)]. In donation after circulatory death (DCD) recipients, DGF [(aHR 1.52 (1.13-2.04)] but not SGF [(aHR 1.55 (1.13-2.13)] was associated with reduced graft survival. Findings were similar for death-censored graft survival. In secondary analyses, SGFwas associated with reduced patient survival in living donor recipients. SGF and DGF were associated with lower 12-month eGFR for all donor types. DGF increased the odds of rejection for all donor types; for SGF this association was significant only for DBD recipients. SGF is associated with adverse outcomes in live donor and DBD kidney recipients.

Background: The number of donors from donation after circulatory determination of death (DCDD) has increased by at least 4-fold over the past decade. This study evaluated the association between the antecedent cardiac arrest status of controlled DCDD donors and the risk of delayed graft function (DGF).Methods: Using data from the Australia and New Zealand Dialysis and Transplant, the associations between antecedent cardiac arrest status of DCDD donors before withdrawal of cardiorespiratory support, DGF, posttransplant estimated glomerular filtration rate (eGFR), and allograft loss were examined using adjusted logistic, linear mixed modeling, and cox regression, respectively. Among donors who experienced cardiac arrest, we evaluated the association between duration and unwitnessed status of arrest and DGF.Results: A total of 1173 kidney transplant recipients received DCDD kidneys from 646 donors in Australia between 2014 and 2019. Of these, 335 DCDD had antecedent cardiac arrest. Compared with recipients of kidneys from donors without antecedent cardiac arrest, the adjusted odds ratio (95% confidence interval) for DGF was 0.85 (0.65-1.11) among those with kidneys from donors with cardiac arrest. There was no association between antecedent cardiac arrest and posttransplant eGFR or allograft loss. The duration of cardiac arrest and unwitnessed status were not associated with DGF.Conclusions:This focused analysis in an Australian population showed that the allograft outcomes were similar whether DCDD donors had experienced a prior cardiac arrest, with no associations between duration or unwitnessed status of arrest and risk of DGF. This study thus provides important reassurance to transplant programs and the patients they counsel, to accept kidneys from donors through the DCDD pathway irrespective of a prior cardiac arrest.

Objectives: To quantify the survival benefit of kidney transplantation for Aboriginal and Torres Strait Islander people waitlisted for deceased donor kidney transplantation in Australia.Study design: Retrospective cohort study; analysis of linked data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry, the Australia and New Zealand Organ Donation (ANZOD) registry, and OrganMatch (Australian Red Cross).Setting, participants: All adult Aboriginal and Torres Strait Islander people (18 years or older) who commenced dialysis in Australia during 1 July 2006 - 31 December 2020 and were included in the kidney-only deceased donor transplant waiting list.Main outcome measures: Survival benefit of deceased donor kidney transplantation relative to remaining on dialysis.Results:Of the 4082 Aboriginal and Torres Strait Islander people who commenced dialysis, 450 were waitlisted for kidney transplants (11%), of whom 323 received deceased donor transplants. Transplantation was associated with a significant survival benefit compared with remaining on dialysis after the first 12 months (adjusted hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20-0.73). This benefit was similar to that for waitlisted non-Indigenous people who received deceased donor kidney transplants (adjusted HR, 0.47; 95% CI, 0.40-0.57; Indigenous status interaction: P = 0.22).Conclusions: From twelve months post-transplantation, deceased donor transplantation provides a survival benefit for Aboriginal and Torres Strait Islander people. Our findings provide evidence that supports efforts to promote the waitlisting of Aboriginal and Torres Strait Islander people who are otherwise eligible for transplantation.

Rationale & objective: There is limited information about the association between primary kidney disease and donor relatedness with transplant outcomes. This study addresses this gap by evaluating clinical outcomes after kidney transplantation in recipients of living donor kidneys as a function of primary kidney disease type and donor relatedness in Australia and New Zealand.Study design: Retrospective observational study.Setting & participants: Kidney transplant recipients who received allografts from living donors between January 1, 1998, and December 31, 2018, as recorded in the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA).Exposures: Primary kidney disease type categorized as majority monogenic, minority monogenic, or other primary kidney disease based on disease heritability as well as donor relatedness.Outcome: Primary kidney disease recurrence, graft failure.Analytical approach: Kaplan-Meier analysis and Cox proportion hazards regression to generate hazard ratios for primary kidney disease recurrence, allograft failure, and mortality. Partial likelihood ratio test was used to examine possible interactions between primary kidney disease type and donor relatedness for both study outcomes.Results: Among 5,500 live donor kidney transplant recipients, majority monogenic (adjusted HR, 0.58, P<0.001) and minority monogenic primary kidney diseases (adjusted HR, 0.64, P<0.001) were associated with reduced primary kidney disease recurrence compared with other primary kidney diseases. Majority monogenic primary kidney disease was also associated with reduced allograft failure (adjusted HR, 0.86, P=0.04) compared with other primary kidney diseases. Donor relatedness was not associated with primary kidney disease recurrence nor graft failure. No interaction was detected between primary kidney disease type and donor relatedness for either study outcome.Limitations: Potential misclassification of primary kidney disease type, incomplete ascertainment of primary kidney disease recurrence, unmeasured confounding.Conclusions: Monogenic primary kidney disease is associated with lower rates of primary kidney disease recurrence and allograft failure. Donor relatedness was not associated with allograft outcomes. These results may inform pretransplant counseling and live donor selection.Plain-language summary: There are theoretical concerns that live-donor kidney transplants may be associated with increased risks of kidney disease recurrence and transplant failure due to unmeasurable shared genetic factors between the donor and the recipient. This study analyzed data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry and showed that, although disease type was associated with the risk of disease recurrence and transplant failure, donor relatedness did not impact transplant outcomes. These findings may inform pretransplant counseling and live donor selection.

Objectives: To assess the impact of the 2009 National Reform Program for organ donation in Australia on the number and characteristics of organ donors under 16 years of age.Design, setting, participants: Retrospective observational time series study; analysis of Australia and New Zealand Organ Donation (ANZOD) registry data for all consented potential deceased organ donors under 16 years of age during 2000-2019, and of numbers of donors aged 16 years or more reported in ANZOD annual reports.Main outcome measures: Difference between 2000-2008 (pre-reform) and 2009-2019 (reform period) in annual organ donor rates (donors per million population), by age group (under 16 years, 16 years or more), reported as incidence rate ratio (IRR).Secondary outcomes: Differences in child donor characteristics during 2000-2008 and 2009-2019.Results: During 2000-2019, 400 children under 16 years of age were consented potential deceased organ donors, of whom 374 were actual deceased donors (94%): 146 during 2000-2008, 228 during 2009-2019. The median annual rate was 3.3 (interquartile range [IQR], 3.0-4.3) actual donors per million population during 2000-2008 and 4.2 (IQR, 3.6-5.2) donors per million population during 2009-2019 (IRR, 1.15; 95% confidence interval [CI], 0.93-1.42). In contrast, the difference between the two periods was statistically significant for donors aged 16 years or more, rising from 11.7 (IQR, 11.2-11.8) to 19.9 (IQR, 18.3-24.4) actual donors per million population (IRR, 1.75; 95% CI, 1.66-1.85). The median age of actual organ donors under 16 was similar during 2000-2008 (11 years; IQR, 7-14 years) and 2009-2019 (10 years; IQR, 4-14 years), as was the proportion of donors in this age group under 10 kg (2000-2008: four of 146, 3%; 2009-2019: 14 of 228, 6%).Conclusions: Despite its overall effect on organ donation rates, the National Reform Program was not effective in increasing the numbers of donors under 16 years of age. Relying on broad initiatives for adult donors may not be appropriate for achieving this aim.

Background: While intra-operative duplex ultrasound scanning can be readily performed in renal transplantation, the value of this intervention in routine practice is not established.Methods: Three hundred thirty-one consecutive single renal transplants in adult recipients underwent intraoperative scanning at implantation. Early graft losses were compared with those recorded in the ANZDATA Registry.Results: Nine overt vascular abnormalities were corrected prior to scanning. Four further suspected venous outflow restrictions were confirmed by ultrasound and revised. Another 11 major vascular revisions were performed following intraoperative ultrasound consisting of 7 otherwise unsuspected inflow abnormalities, all corrected, and 4 anastomoses redone to reposition the graft. Thirty-two (9.7%) grafts were repositioned under ultrasound guidance to improve cortical perfusion but without vascular revision. One graft with hyperacute rejection was explanted 4 days postimplantation and one graft with primary nonfunction remained well perfused. Two patients died within 90 days, both with functioning grafts. Twenty-three grafts were re-explored within 7 days, including 9 solely for graft hypoperfusion. There were no postoperative arterial thromboses and, at re-exploration, no arterial anastomoses required revision. There were no postoperative venous thromboses, although one venous anastomosis was revised. No grafts were lost within 90 days for surgical or technical reasons compared with 76 (1.0%) of 7603 contemporaneous grafts in the ANZDATA Registry (P = .077 Fisher's exact test, P = .069 χ2 test).Conclusions: The routine use of intraoperative ultrasound appears to be of benefit by identifying otherwise unrecognized vascular abnormalities, leading to a reduction in early graft losses because of surgical factors.

Background: Parental donor kidney transplantation is the most common treatment option for children and adolescents with kidney failure. Emerging data from observational studies have reported improved short- and medium-term allograft outcomes in recipients of paternal compared to maternal donors. The INCEPTION study aims to identify potential differences in immunological compatibility between maternal and paternal donor kidneys and ascertain how this affects kidney allograft outcomes in children and adolescents with kidney failure.Methods: This longitudinal observational study will recruit kidney transplant recipients aged ≤18 years who have received a parental donor kidney transplant across 4 countries (Australia, New Zealand, United Kingdom and the Netherlands) between 1990 and 2020. High resolution human leukocyte antigen (HLA) typing of both recipients and corresponding parental donors will be undertaken, to provide an in-depth assessment of immunological compatibility. The primary outcome is a composite of de novo donor-specific anti-HLA antibody (DSA), biopsy-proven acute rejection or allograft loss up to 60-months post-transplantation. Secondary outcomes are de novo DSA, biopsy-proven acute rejection, acute or chronic antibody mediated rejection or Chronic Allograft Damage Index (CADI) score of > 1 on allograft biopsy post-transplant, allograft function, proteinuria and allograft loss. Using principal component analysis and Cox proportional hazards regression modelling, we will determine the associations between defined sets of immunological and clinical parameters that may identify risk stratification for the primary and secondary outcome measures among young people accepting a parental donor kidney for transplantation. This study design will allow us to specifically investigate the relative importance of accepting a maternal compared to paternal donor, for families deciding on the best option for donation.Discussion: The INCEPTION study findings will explore potentially differential immunological risks of maternal and paternal donor kidneys for transplantation among children and adolescents. Our study will provide the evidence base underpinning the selection of parental donor in order to achieve the best projected long-term kidney transplant and overall health outcomes for children and adolescents, a recognized vulnerable population.Trial registration: The INCEPTION study has been registered with the Australian New Zealand Clinical Trials Registry, with the trial registration number of ACTRN12620000911998 (14th September 2020).

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.