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.

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.

The IDEAL trial in Australia and New Zealand: clinical and economic impact.

BACKGROUND: The impact of research findings on clinical practice usually remains uncertain and unmeasured. To address this problem, we examined the long-term clinical and economic impact of the Initiating Dialysis Early and Late (IDEAL) trial using data from the Australia and New Zealand Dialysis and Transplant Registry. METHODS: We performed a registry-based study including all incident adult dialysis patients in Australia and New Zealand from July 2000 to June 2018. A piecewise linear regression model was used to examine differences in mean estimated glomerular filtration rate (eGFR) at dialysis commencement for the years prior to (2000-2010) and following (2010-2018) publication of the IDEAL trial results. The return on investment (ROI) was calculated using the total cost of performing the IDEAL trial and the cost or savings accruing in Australia and New Zealand from changes in dialysis initiation practice. RESULTS: From July 2000 to June 2010, mean eGFR at dialysis commencement increased at a rate of 0.21 mL/min/1.73 m2/year [95% confidence interval (CI) 0.19-0.23]. After the IDEAL trial results were published, mean eGFR at dialysis commencement did not show any temporal change [-0.01 mL/min/1.73 m2/year (95% CI -0.03-0.01)]. The ROI of the IDEAL trial was AU$35.70/AU$1 spent, an estimated savings to the Australian and New Zealand health systems of up to AU$84 million/year. CONCLUSIONS: The previous trend to higher eGFR at dialysis commencement changed following publication of the IDEAL trial results to a steady eGFR that has continued for a decade, avoiding unnecessary dialysis treatments and accruing savings to the Australian and New Zealand health systems.

Access to waitlisting for deceased donor kidney transplantation in Australia.

AIM: A detailed analysis of waitlisting for deceased donor kidney transplantation in Australia has not previously been reported. We aimed to determine if patient characteristics associated with waitlisting identify areas of potential inequality in access to transplantation in Australia. METHODS: A competing risk time-to-event model was used to determine predictors of waitlisting for all adult incident renal replacement therapy patients in Australia between 2006 and 2015. Secondary analysis was performed to determine predictors of overall access to transplantation (using a combined outcome of waitlisting and living donor transplantation). RESULTS: The cohort consisted of 21 231 patients with a median age of 63 years. Overall, 4361 (20.5%) were waitlisted and 1239 (5.8%) received a living donor transplant without being previously waitlisted. Primary analysis revealed that medical comorbidities, older age, smoking status and body mass index were all significant predictors of waitlisting and that and there was variation in waitlisting practice across states Despite adjustment for the above factors, demographic characteristics, including Indigenous ethnicity (subdistribution hazard ratios (SHR) 0.46 (95% confidence interval (CI) 0.38-0.55)), female gender (SHR 0.85 (95% CI 0.80, 0.91)) and residence in a regional area (SHR 0.88 (95% CI 0.81-0.95)) were also associated with a lower likelihood of waitlisting. Secondary analysis showed younger age and higher socio-economic advantage were additional predictors of overall access to transplantation, driven by higher rates of living donor transplantation. CONCLUSION: Demographic as well as clinical characteristics are associated with reduced likelihood of waitlisting for kidney transplantation in Australia. Further analysis and auditing should be considered to determine if this reflects other unmeasured factors or highlights a need to address inequality.

Identifying Outcomes that Are Important to Living Kidney Donors: A Nominal Group Technique Study.

BACKGROUND AND OBJECTIVES: Living kidney donor candidates accept a range of risks and benefits when they decide to proceed with nephrectomy. Informed consent around this decision assumes they receive reliable data about outcomes they regard as critical to their decision making. We identified the outcomes most important to living kidney donors and described the reasons for their choices. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Previous donors were purposively sampled from three transplant units in Australia (Sydney and Melbourne) and Canada (Vancouver). In focus groups using the nominal group technique, participants identified outcomes of donation, ranked them in order of importance, and discussed the reasons for their preferences. An importance score was calculated for each outcome. Qualitative data were analyzed thematically. RESULTS: Across 14 groups, 123 donors aged 27-78 years identified 35 outcomes. Across all participants, the ten highest ranked outcomes were kidney function (importance=0.40, scale 0-1), time to recovery (0.27), surgical complications (0.24), effect on family (0.22), donor-recipient relationship (0.21), life satisfaction (0.18), lifestyle restrictions (0.18), kidney failure (0.14), mortality (0.13), and acute pain/discomfort (0.12). Kidney function and kidney failure were more important to Canadian participants, compared with Australian donors. The themes identified included worthwhile sacrifice, insignificance of risks and harms, confidence and empowerment, unfulfilled expectations, and heightened susceptibility. CONCLUSIONS: Living kidney donors prioritized a range of outcomes, with the most important being kidney health and the surgical, lifestyle, functional, and psychosocial effects of donation. Donors also valued improvements to their family life and donor-recipient relationship. There were clear regional differences in the rankings.

Survival and Quality of Life Impact of a Risk-based Allocation Algorithm for Deceased Donor Kidney Transplantation.

BACKGROUND: To determine the incremental gains in graft and patient survival under a risk-based, deceased donor kidney allocation compared with the current Australian algorithm. METHODS: Risk-based matching algorithms were applied to first graft, kidney only recipients (n = 7513) transplanted in Australia between 1994 and 2013. Probabilistic models were used to compare the waiting time, life, and QALYs and graft years between the 8 risk-based allocation strategies against current practice. RESULTS: Compared with current practice, Kidney Donor Risk Index-Estimated Posttransplant Survival matching of the lowest 20% of scores reduced median waiting time by 0.64 years (95% confidence interval [CI], 0.52-0.73) for recipients aged 30 years or younger, but increased waiting time by 0.94 years (95% CI, 0.79-1.09) for recipients older than 60 years. Among all age groups, the greatest gains occurred if Kidney Donor Risk Index-Estimated Posttransplant Survival matching of the lowest 30% of scores was used, incurring a median overall gain of 0.63 (95% CI, 0.03-1.25) life years and 0.78 (95% CI, 0.30-1.26) graft years compared with the current practice. A median gain in survival of 1.91 years for younger recipients (aged 30-45 years) was offset by a median reduction in survival (by 0.95 life years) among the older recipients. Prioritization of lower-quality donor kidneys for older candidates reduced the waiting time for recipients older than 45 years, but no changes in graft and patient survivals were observed. CONCLUSIONS: Risk-based matching engendered a moderate, overall increase in graft and patient survivals, accrued through benefits for recipients 45 years or younger but disadvantage to recipients older than 60 years.

The Lived Experience of "Being Evaluated" for Organ Donation: Focus Groups with Living Kidney Donors.

BACKGROUND AND OBJECTIVES: Comprehensive evaluations are required to safeguard voluntarism and minimize harm to living kidney donors. This process is lengthy, invasive, and emotionally challenging, with up to one fifth of potential donors opting out. We aimed to describe donors' experiences of the evaluation process. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted 14 focus groups involving 123 kidney donors who completed donation from three transplant centers (Australia and Canada). Transcripts were analyzed thematically. RESULTS: We identified six themes reflecting donors' experiences of evaluation. The themes that related to perseverance included emotional investment (prioritizing the recipient's health, desperation for a normal life, protecting eligibility, shame of disappointing others, and overcoming opposition), undeterred by low risks (medical confidence and protection, worthwhile gamble, inherent invincibility, and normalizing risks), and mental preparation (avoiding regret, resolving decisional ambivalence, and managing expectations of recovery). The challenges included underlying fears for health (processing alarming information, unsettling uncertainty, and preoperative panic), system shortfalls (self-advocacy in driving the process, stressful urgency, inconsistent framing of safety, unnerving bodily scrutiny, questioning risk information, and draining finances); and lifestyle interference (living in limbo, onerous lifestyle disruption, and valuing flexibility). CONCLUSIONS: Previous donors described an emotional investment in donating and determination to protect their eligibility, despite having concerns for their health, financial and lifestyle disruption, and opposition from their family or community. Our findings suggest the need to prepare donors for surgery and recovery, minimize anxiety and lifestyle burdens, ensure that donors feel comfortable expressing their fears and concerns, reduce unnecessary delays, and make explicit the responsibilities of donors in their assessment process.

Research priority setting in organ transplantation: a systematic review.

Barriers to access and long-term complications remain a challenge in transplantation. Further advancements may be achieved through research priority setting with patient engagement to strengthen its relevance. We evaluated research priority setting in solid organ transplantation and described stakeholder priorities. Databases were searched to October 2016. We synthesized the findings descriptively. The 28 studies (n = 2071 participants) addressed kidney [9 (32%)], heart [7 (25%)], liver [3 (11%)], lung [1 (4%)], pancreas [1 (4%)], and nonspecified organ transplantation [7 (25%)] using consensus conferences, expert panel meetings, workshops, surveys, focus groups, interviews, and the Delphi technique. Nine (32%) reported patient involvement. The 336 research priorities addressed the following: organ donation [43 priorities (14 studies)]; waitlisting and allocation [43 (10 studies)]; histocompatibility and immunology [31 (8 studies)]; immunosuppression [21 (10 studies)]; graft-related complications [38 (13 studies)]; recipient (non-graft-related) complications [86 (14 studies)]; reproduction [14 (1 study)], psychosocial and lifestyle [49 (7 studies)]; and disparities in access and outcomes [10 (4 studies)]. The priorities identified were broad but only one-third of initiatives engaged patients/caregivers, and details of the process were lacking. Setting research priorities in an explicit manner with patient involvement can guide investment toward the shared priorities of patients and health professionals.

Progress in Transplantation: Will It Be Achieved in Big Steps or by Marginal Gains?

A wish for progress in transplantation assumes that there are needs not met by the currently available therapy and that the barriers to resolving the problems can be surmounted. There are 5 major unmet needs: the potential to avoid transplantation either by prevention of disease or provision of an alternative to natural biological organ replacement; geographic heterogeneity of access to, and quality of, transplantation; availability of transplantation to those in need of it; survival of the patient and the transplant; and the avoidance of adverse effects of immunosuppression. During the past 50 years, there have been advances on at least 4 of these 5 fronts that illustrate the interplay of "big steps" and "marginal gains" in the following areas: surgical technique, testing the immunologic barriers, introduction of chemical and biological immunosuppression, and prophylaxis for microbial infections. The potential for further improvement comes in 5 major areas: blood biomarkers for monitoring of rejection, drug-free transplantation through the development of stable tolerance, eliminating the impact of ischemia-reperfusion injury, xenotransplantation of porcine kidneys, and finally, the possibility of autologous regeneration of functioning kidney tissue to treat advanced kidney disease.

Patient experiences of training and transition to home haemodialysis: A mixed-methods study.

AIM: This study aims to describe patients' perspectives on the transition to home haemodialysis. METHODS: Up to three sequential semi-structured interviews were conducted with 20 patients during the transition to home haemodialysis at an Australian renal unit. Transcripts were analysed thematically. Participants completed a satisfaction questionnaire after commencing home haemodialysis. RESULTS: We identified six themes: persevering despite trepidations (diminishing intimidation of machinery, acquiescing to fatal risks, reconciling fears of cannulation, dispelling concerns of neglect and tolerating necessary concessions); optimizing the learning pathway (practising problem solving, learning from mistakes, grasping technical complexity, minimizing cognitive overload and progressing at own pace); developing confidence (believing in own abilities, adapting to independence, depending on caregiver partnership and faith in crisis support); interrupted transition momentum (lacking individual attention, language barriers, installation delays, interfering illness and complications and acclimatizing to new conditions); noticing immediate gains (reclaiming lifestyle normality, satisfying self-sufficiency, personalizing treatment regime and thriving in a positive environment); and depleting resources and energy (exhaustion with gruelling routine, confronting medicalization of the home, draining financial reserves and imposing family burden). Fewer than 30% of respondents indicated low satisfaction with staff availability domains, staff interpersonal domains or technical domains. CONCLUSION: Home haemodialysis training fosters confidence in patients; however, many patients experience stress because of medical isolation, treatment responsibilities, family impositions and financial difficulties. Addressing patient's on-going psychosocial concerns may alleviate burdens on patients and their families during the transition to home haemodialysis.

Statement of the Declaration of Istanbul Custodian Group Regarding Payments to Families of Deceased Organ Donors.

Governmental and private programs that pay next of kin who give permission for the removal of their deceased relative's organs for transplantation exist in a number of countries. Such payments, which may be given to the relatives or paid directly for funeral expenses or hospital bills unrelated to being a donor, aim to increase the rate of donation. The Declaration of Istanbul Custodian Group-in alignment with the World Health Organization Guiding Principles and the Council of Europe Convention Against Trafficking in Human Organs-has adopted a new policy statement opposing such practices. Payment programs are unwise because they produce a lower rate of donations than in countries with voluntary, unpaid programs; associate deceased donation with being poor and marginal in society; undermine public trust in the determination of death; and raise doubts about fair allocation of organs. Most important, allowing families to receive money for donation from a deceased person, who is at no risk of harm, will make it impossible to sustain prohibitions on paying living donors, who are at risk. Payment programs are also unethical. Tying coverage for funeral expenses or healthcare costs to a family allowing organs to be procured is exploitative, not "charitable." Using payment to overcome reluctance to donate based on cultural or religious beliefs especially offends principles of liberty and dignity. Finally, while it is appropriate to make donation "financially neutral"-by reimbursing the added medical costs of evaluating and maintaining a patient as a potential donor-such reimbursement may never be conditioned on a family agreeing to donate.

Maternal compared with paternal donor kidneys are associated with poorer graft outcomes after kidney transplantation.

Noninherited maternal human leukocyte antigens may be less detrimental on allograft outcomes after kidney transplantation compared with noninherited paternal antigens, but this association in the era of modern immunosuppression remains unknown. Here we determine the association between parental donor kidneys, acute rejection, and graft failure in primary live-donor parental kidney transplant recipients using data from the Australia and New Zealand Dialysis and Transplant Registry between 1997 and 2012. Of the 1139 recipients followed for a median of 7.2 years (8588 person-years), 652 received kidneys from maternal donors. Compared with paternal donor kidneys, maternal donor kidneys were associated with a significantly increased risk of acute rejection (adjusted odds ratio 1.54; 95% confidence interval [CI], 1.14-2.07) and significant overall graft loss. The latter was confined to recipients who have experienced acute rejection (adjusted hazard ratio 1.60; 95%CI, 1.05-2.43) but not in those who did not experience acute rejection. Thus, our study suggests that recipients of maternal donor kidneys have a greater risk of rejection and graft loss. Hence, clinicians and patients should be cognizant of this association when determining which of the 2 parental donors is most suitable for transplantation.

Nephrologists' Perspectives on Recipient Eligibility and Access to Living Kidney Donor Transplantation.

BACKGROUND: Wide variations in access to living kidney donation are apparent across transplant centers. Such disparities may be in part explained by nephrologists' beliefs and decisions about recipient eligibility. This study aims to describe nephrologists' attitudes towards recipient eligibility and access to living kidney donor transplantation. METHODS: Face-to-face semistructured interviews were conducted from June to October 2013 with 41 nephrologists from Australia and New Zealand. Transcripts were analyzed thematically. RESULTS: We identified five major themes: championing optimal recipient outcomes (maximizing recipient survival, increasing opportunity, accepting justified risks, needing control and certainty of outcomes, safeguarding psychological wellbeing), justifying donor sacrifice (confidence in reasonable utility, sparing the donor, ensuring reciprocal donor benefit), advocating for patients (being proactive and encouraging, addressing ambivalence, depending on supportive infrastructure, avoiding selective recommendations), maintaining professional boundaries (minimizing conflict of interest, respecting shared decision-making, emphasizing patient accountability, restricted decisional power, protecting unit interests), and entrenched inequities (exclusivity of living donors, inherently advantaging self-advocates, navigating language barriers, increasing center transparency, inevitable geographical disadvantage, understanding cultural barriers). CONCLUSIONS: Nephrologists' decisions about recipient suitability for living donor transplantation aimed to achieve optimal recipient outcomes, but were constrained by competing priorities to ensure reasonable utility derived from the donor kidney and protect the integrity of the transplant program. Comprehensive guidelines that provide explicit recommendations for complex medical and psychosocial risk factors might promote more equitable and transparent decision-making. Psychosocial support and culturally sensitive educational resources are needed to help nephrologists advocate for disadvantaged patients and address disparities in access to living kidney donor transplantation.

The relative benefits and costs of solid phase bead technology to detect preformed donor specific antihuman leukocyte antigen antibodies in determining suitability for kidney transplantation.

BACKGROUND: Screening for donor-specific anti-HLA antibodies (DSA) using bead-based multiplex assays to determine transplant suitability is standard practice in many countries. We compared the health benefits and costs of screening preformed DSA using bead-based assay as an add-on test to complement-dependent cytotoxicity (CDC) crossmatch with CDC crossmatch alone, and determined the optimal threshold to determine transplant suitability. METHODS: Three probabilistic Markov models were developed to compare bead-based assay with CDC and CDC alone. The model assumed a hypothetical cohort of 10,000 patients who received only a single kidney transplant and terminated when all patients were deceased. RESULTS: Assuming transplantation was permitted for recipients with no DSA or with a DSA mean fluorescence intensity (MFI) value of 500 or less, screening by bead-based assay and CDC saved 6.5 grafts and U.S. $1,192,303 per 100 transplants compared with CDC alone. If the thresholds were increased to an MFI of 2000 or less and 5000 or less, an extra 6.4 and 6.1 grafts would be saved, with cost savings of U.S. $867,203 and U.S. $830,664 per 100 transplants compared with CDC alone. The total number of kidney transplants performed would have increased by 8 and 9, respectively, but at the expense of an extra 0.1 and 0.4 graft lost per 100 transplants after 5 years. CONCLUSIONS: Screening using bead-based assay is cost-saving and improves graft outcomes. The greatest benefits and cost-savings are achieved if transplantation occurs at a threshold of MFI of 500 or less or in those without preformed DSA. Increasing the threshold to an MFI of 2000 or less may provide an acceptable balance for improving transplant eligibility without compromising longer-term outcomes.

'Suspended in a paradox'-patient attitudes to wait-listing for kidney transplantation: systematic review and thematic synthesis of qualitative studies.

Patients on waiting lists for kidney transplantation have higher mortality rates and have specific anxieties about their eligibility, process, and outcomes of wait-listing. We aimed to describe patient experiences and attitudes to wait-listing for kidney transplantation. Electronic databases were searched to September 2014. Thematic synthesis was used to analyze the findings. From 22 studies (n = 795 patients), we identified six themes: accepting the only option (chance to regain normality, avoiding guilt, impulsive decision-making); maintaining hope (determined optimism, appreciating a fortuitous gift, enduring for optimal outcomes, trust in clinical judgment); burden of testing (strenuous commitment, losing the battle, medical mistrust); permeating vulnerability (eligibility enigma, being threatened, angst of timing uncertainty, desperate urgency, living in limbo, spiraling doubt and disappointment, residual ambivalence); deprived of opportunity (unfairly dismissed, unexpected disqualification, self-resignation and acceptance, jealousy, suspicious of inequity); and moral guilt (awaiting someone's death, questioning deservingness). The waiting list offered hope of restored normality. However, the demands of workup, uncertainty about eligibility, and waiting times that exceeded expectations impelled patients to disillusionment, despair, and suspicion of inequity. Managing patient expectations and ensuring transparency of wait-listing and allocation decisions may allay patient disappointment and skepticism, to improve patient satisfaction and treatment outcomes.

Focus group study of public opinion about paying living kidney donors in Australia.

BACKGROUND AND OBJECTIVES: The unmet demand for kidney transplantation has generated intense controversy about introducing incentives for living kidney donors to increase donation rates. Such debates may affect public perception and acceptance of living kidney donation. This study aims to describe the range and depth of public opinion on financial reimbursement, compensation, and incentives for living kidney donors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Twelve focus groups were conducted with 113 participants recruited from the general public in three Australian states in February 2013. Thematic analysis was used to analyze the transcripts. RESULTS: Five themes were identified: creating ethical impasses (commodification of the body, quandary of kidney valuation, pushing moral boundaries), corrupting motivations (exposing the vulnerable, inevitable abuse, supplanting altruism), determining justifiable risk (compromising kidney quality, undue harm, accepting a confined risk, trusting protective mechanisms, right to autonomy), driving access (urgency of organ shortage, minimizing disadvantage, guaranteeing cost-efficiency, providing impetus, counteracting black markets), and honoring donor deservingness (fairness and reason, reassurance and rewards, merited recompense). Reimbursement and justifiable recompense are considered by the Australian public as a legitimate way of supporting donors and reducing disadvantage. Financial payment beyond reimbursement is regarded as morally reprehensible, with the potential for exploitative commercialism. Some contend that regulated compensation could be a defensible strategy to increased donation rates provided that mechanisms are in place to protect donors. CONCLUSIONS: The perceived threat to community values of human dignity, goodwill, and fairness suggests that there could be strong public resistance to any form of financial inducements for living kidney donors. Policy priorities addressing the removal of disincentives may be more acceptable to the public.

Perspectives of Transplant Professionals on the Values, Ethics, and Challenges of Living Kidney Donor Evaluation in Asia.

BACKGROUND: Deceased donor rates in Asia are among the lowest in the world. This has necessitated a reliance on living kidney donation, which has given rise to concerns about donor motivation and assessment in this region. We aimed to describe transplant professional perspectives on living kidney donor evaluation in Asia. METHODS: Face-to-face, semistructured interviews were conducted with 53 transplant professionals (nephrologists [n = 21], surgeons/urologists [n = 17], coordinators [n = 7], social workers [n = 5], ethicists [n = 2], psychologist [n = 1]) from 20 centers in 10 countries. Transcripts were analyzed thematically to identify themes. RESULTS: The theme of traversing vulnerability overarched 4 themes. Vigilance against exploitation of the vulnerable meant mitigating the threat of commercial transplantation, combating disparities, and verifying volunteerism. Maintaining clarity of professional roles encompassed the perceived necessity of legal safeguards to determine legitimacy of relationships, ensuring informed consent, demarcating responsibilities, minimizing conflict of interest, meeting community expectations, and resolving ambivalence regarding donor risk. Societal plight driving caution about living kidney donor assessment was emphasized in the context of poverty and desperation, higher risk of disease, and lack of social security. Navigating sociocultural barriers acknowledged the centrality of the family, economic priorities, distrust in modern medicine, generational traditions, and emotional opacity limiting their ability to gauge donor motivation. CONCLUSIONS: Moral, professional, sociocultural and societal vulnerabilities contribute to the barriers and ethical quandaries in living kidney donation in Asia. Strategies are needed to address culturally based anxieties and disparities in living donation. Transplant professionals depend on strong legislation and policies to prevent exploitation of living donors.