Surveillance for donor-derived infections in Australia.

BACKGROUND: Systems for quality and safety assurance in organ donation and transplantation are vital, especially those that seek to minimize donor disease transmission. Australia has developed a national vigilance and surveillance system to identify, review, and analyze actual and potential donor-derived infections and other disease transmissions. METHODS: The system involves notification of incidents to the Australian Organ and Tissue Authority for review by a Vigilance and Surveillance Expert Advisory Committee (VSEAC). The VSEAC grades incidents, O makes recommendations, and issues communications both publicly and to the clinical donation and transplant sector. RESULTS: Annual notifications have increased since the inception of the system in 2012 until 2022. The vast majority relate to procedural aspects including donor assessment, information/data issues, and the recovery, offer, allocation, preservation and transportation of organs. Possible donor-derived disease accounted for 19% of all notifications, and those related to possible donor-derived infection only 12%. The VSEAC, as a result of reviewing these incidents, has made recommendations resulting in revisions to donor screening, organ allocation, packaging and transportation. The review of incidents has led to changes in clinical guidance for increased viral risk donor assessment, testing, and ensuing organ utilization and recipient surveillance. Guidance has also been reviewed for other infectious risks including strongyloides, human T-lymphotropic virus, and HEV. CONCLUSION: The Australian vigilance and surveillance system has enabled national retrospective reporting and evaluation of serious adverse events or reactions to identify trends and inform processes and guidelines, therefore improving the safety of donation and transplantation.

Moving Boundaries for Improving Organ Transplant Availability.

This brief overview is designed to address the options for increasing organ transplant rates to between 100 and 120 transplanted organs per million population globally. The focus of this review is the data produced through the World Health Organization's Global Observatory on Donation and Transplantation, with consideration for the issues that different countries need to address to achieve higher transplant rates. Without both optimized living donation and optimized deceased donation, rates of transplant are not sufficient to provide for a level of self-dependency for transplant therapy. Deceased donation comprises both donation from donors declared dead after cessation of all functions of the brain and donors declared dead from irreversible cessation of circulation of the blood. The preservation strategies that hold the greatest chance of increasing the utility of marginal and older donors involve normothermic circulation to prevent ischemic damage and potentially restore function of damaged organs. Normothermic in situ perfusion of abdominal organs has demonstrated utility, and consideration must be given to normothermic perfusion of the thoracic organs to improve heart and lung transplants, but this may challenge the legal definitions of death. Each nation must endeavor to increase organ donation capacity across the spectrum of donor types and must address the opportunities that normothermic perfusion of organs at retrieval may offer to alleviate shortages of organs for transplant and provide selfdependency for the communities.

Antecedent Cardiac Arrest Status of Donation After Circulatory Determination of Death (DCDD) Kidney Donors and the Risk of Delayed Graft Function After Kidney Transplantation: A Cohort Study.

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.

Donors With a Prior History of Cancer: Factors of Non-Utilization of Kidneys for Transplantation.

Cancer transmission from deceased donors is an exceedingly rare but potentially fatal complication in transplant recipients. We aimed to quantify the likelihood of non-utilization of kidneys for transplantation from donors with a prior cancer history. We included all intended and actual deceased donors in Australia and New Zealand between 1989 and 2017. Association between prior cancer history and non-utilization of donor kidneys was examined using adjusted logistic regression. Of 9,485 deceased donors, 345 (4%) had a prior cancer history. Of 345 donors with a prior cancer history, 197 (57%) were utilized for transplantation. Donor characteristics of age, sex and comorbidities were similar between utilized and non-utilized donors with prior cancer. The time from cancer to organ donation was similar between utilized and non-utilized donors, irrespective of cancer subtypes. Donors with a prior cancer history were less likely to be utilized [adjusted OR (95% CI) 2.29 (1.68-3.13)] than donors without prior cancer. Of all actual donors, the adjusted OR for non-utilization among those with prior cancer was 2.36 (1.58-3.53). Non-melanoma skin cancer was the most frequent prior cancer type for utilized and non-utilized potential donors. Donors with prior cancers were less likely to be utilized for transplantation, with no discernible differences in cancer characteristics between utilized and non-utilized donors.

Trajectories of systolic blood pressure decline in kidney transplant donors prior to circulatory death and delayed graft function.

Background: Kidneys donated after circulatory death suffer a period of functional warm ischaemia before death, which may lead to early ischaemic injury. Effects of haemodynamic trajectories during the agonal phase on delayed graft function (DGF) is unknown. We aimed to predict the risk of DGF using patterns of trajectories of systolic blood pressure (SBP) declines in Maastricht category 3 kidney donors. Methods: We conducted a cohort study of all kidney transplant recipients in Australia who received kidneys from donation after circulatory death donors, divided into a derivation cohort (transplants between 9 April 2014 and 2 January 2018 [462 donors]) and a validation cohort (transplants between 6 January 2018 and 24 December 2019 [324 donors]). Patterns of SBP decline using latent class models were evaluated against the odds of DGF using a two-stage linear mixed effects model. Results: In the derivation cohort, 462 donors were included in the latent class analyses and 379 donors in the mixed effects model. Of the 696 eligible transplant recipients, 380 (54.6%) experienced DGF. Ten different trajectories, with distinct patterns of SBP decline were identified. Compared with recipients from donors with the slowest decline in SBP after withdrawal of cardiorespiratory support, the adjusted odds ratio (aOR) for DGF was 5.5 [95% confidence interval (CI) 1.38-28.0] for recipients from donors with a steeper decline and lowest SBP [mean 49.5 mmHg (standard deviation 12.5)] at the time of withdrawal. For every 1 mmHg/min reduction in the rate of decline of SBP, the respective aORs for DGF were 0.95 (95% CI 0.91-0.99) and 0.98 (95% CI 0.93-1.0) in the random forest and least absolute shrinkage and selection operator models. In the validation cohort, the respective aORs were 0.95 (95% CI 0.91-1.0) and 0.99 (95% CI 0.94-1.0). Conclusion: Trajectories of SBP decline and their determinants are predictive of DGF. These results support a trajectory-based assessment of haemodynamic changes in donors after circulatory death during the agonal phase for donor suitability and post-transplant outcomes.

Variations in Risk of Cancer and Death From Cancer According to Kidney Allograft Function, Graft Loss, and Return to Dialysis.

BACKGROUND: Cancer incidence and mortality may change with varying kidney allograft function and after graft loss. We aimed to quantify cancer incidence and mortality during periods with a functioning graft and after graft loss. METHODS: We included all adult Australians aged 20 and above who commenced kidney replacement therapy between 1982 and 2014 using data from Australia and New Zealand Dialysis and Transplant Registry. We calculated the standardized incidence ratios and standardized mortality ratios (standardized against the Australian general population) for dialysis patients and transplant recipients during periods with a functioning graft and after graft loss. RESULTS: A total of 44 765 dialysis patients without transplants, 13 443 with first kidney transplants, 2951 after first graft loss, 1010 with second transplants, and 279 after second graft loss were followed for 274 660 patient-years. Cancer incidence and mortality (per 100 000 patient-years) were 1564 and 760 in dialysis patients, 1564 and 689 in recipients of first transplants, 1188 and 390 after first graft loss, 1525 and 693 after second transplants, and 1645 and 779 after second graft loss. Cancer standardized incidence ratios and standardized mortality ratios (95% confidence intervals) were 1.15 (1.11-1.20) and 1.29 (1.21-1.36) for dialysis patients, 2.03 (1.94-2.13) and 2.50 (2.33-2.69) for recipients following their first transplant, 1.55 (1.29-1.85) and 1.40 (1.00-1.90) after first graft loss, 2.18 (1.79-2.63) and 3.00 (2.23-3.96) for second transplants, 2.59 (1.56-4.04) and 3.82 (1.75-7.25) after second graft loss. CONCLUSIONS: In kidney transplant recipients, cancer incidence and mortality are highest during periods with a functioning graft and remained higher than in the general population even after graft loss.

Controversies in Living Kidney Donation.

The most precious gift that can be given is, arguably, a living organ to a person in need of replacement because of failure of that organ. Kidney transplantation remains the best modality of renal replacement therapy and there is an ever-increasing demand for organ donation. The inability of cadaveric organ donation to meet the needs of the increasing numbers of patients on global waiting lists highlights the important needs for alternate sources for kidneys such as those from living kidney donation. However, living donor kidney transplantation has been a focus of intense debate, with ethical concerns and controversies emanating from operating on an individual who does not need, and is put at a small but quantifiable risk from, the surgical intervention. Furthermore, health care systems across the world also are funded with different levels of national and individual affordability, leading to health inequalities for the sick and risks of exploitation for the poor, especially through commercialization of transplantation. This article highlights some of these contemporary ethical concerns and controversies in living organ donation.

Nonutilization of Kidneys From Donors After Circulatory Determinant of Death.

Background: The expansion of donation after circulatory determination of death (DCDD) programs and unmet demands for kidney transplantation indicate that there is a need to improve the efficiency and utilization of these organs. Methods: We studied all DCDD donors retrieved for kidney transplantation in Australia between 2014 and 2019 and determined the factors associated with nonutilization using least absolute shrinkage and selection operator and random forest models. Self-organizing maps were used to group these donors into clusters with similar characteristics and features associated with nonutilization were defined. Results: Of the 762 DCDD donors, 116 (15%) were not utilized for kidney transplantation. Of the 9 clusters derived from self-organizing map, 2 had the highest proportions of nonutilized kidneys. Factors for nonutilization (adjusted odds ratio [95% confidence interval], per SD increase) were duration from withdrawal of cardiorespiratory support till death (1.38 [1.16-1.64]), admission and terminal serum creatinine (1.43 [1.13-1.85]) and (1.41 [1.16-1.73]). Donor kidney function and duration of warm ischemia were the main factors for clinical decisions taken not to use kidneys from DCDD donors. Conclusions: Donor terminal kidney function and the duration of warm ischemia are the key factors for nonutilization of DCDD kidneys. Strategies to reduce the duration of warm ischemia and improve post-transplant recipient kidney function may reduce rates of nonutilization.

Factors Associated With Advanced Colorectal Neoplasia in Patients With CKD.

RATIONALE & OBJECTIVE: The risk of developing colorectal cancer in patients with chronic kidney disease (CKD) is twice that of the general population, but the factors associated with colorectal cancer are poorly understood. The aim of this study was to identify factors associated with advanced colorectal neoplasia in patients with CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Patients with CKD stages 3-5, including those treated with maintenance dialysis or transplantation across 11 sites in Australia, New Zealand, Canada, and Spain, were screened for colorectal neoplasia using a fecal immunochemical test (FIT) as part of the Detecting Bowel Cancer in CKD (DETECT) Study. EXPOSURE: Baseline characteristics for patients at the time of study enrollment were ascertained, including duration of CKD, comorbidities, and medications. OUTCOME: Advanced colorectal neoplasia was identified through a 2-step verification process with colonoscopy following positive FIT and 2-year clinical follow-up for all patients. ANALYTICAL APPROACH: Potential factors associated with advanced colorectal neoplasia were explored using multivariable logistic regression. Sensitivity analyses were performed using grouped LASSO (least absolute shrinkage and selection operator) logistic regression. RESULTS: Among 1,706 patients who received FIT-based screening-791 with CKD stages 3-5 not receiving kidney replacement therapy (KRT), 418 receiving dialysis, and 497 patients with a functioning kidney transplant-117 patients (6.9%) were detected to have advanced colorectal neoplasia (54 with CKD stages 3-5 without KRT, 34 receiving dialysis, and 29 transplant recipients), including 9 colorectal cancers. The factors found to be associated with advanced colorectal neoplasia included older age (OR per year older, 1.05 [95% CI, 1.03-1.07], P<0.001), male sex (OR, 2.27 [95% CI, 1.45-3.54], P<0.001), azathioprine use (OR, 2.99 [95% CI, 1.40-6.37], P=0.005), and erythropoiesis-stimulating agent use (OR, 1.92 [95% CI, 1.22-3.03], P=0.005). Grouped LASSO logistic regression revealed similar associations between these factors and advanced colorectal neoplasia. LIMITATIONS: Unmeasured confounding factors. CONCLUSIONS: Older age, male sex, erythropoiesis-stimulating agents, and azathioprine were found to be significantly associated with advanced colorectal neoplasia in patients with CKD.