Deceased donors as nondirected donors in kidney paired donation.

As proof of concept, we simulate a revised kidney allocation system that includes deceased donor (DD) kidneys as chain-initiating kidneys (DD-CIK) in a kidney paired donation pool (KPDP), and estimate potential increases in number of transplants. We consider chains of length 2 in which the DD-CIK gives to a candidate in the KPDP, and that candidate's incompatible donor donates to theDD waitlist. In simulations, we vary initial pool size, arrival rates of candidate/donor pairs and (living) nondirected donors (NDDs), and delay time from entry to the KPDP until a candidate is eligible to receive a DD-CIK. Using data on candidate/donor pairs and NDDs from the Alliance for Paired Kidney Donation, and the actual DDs from the Scientific Registry of Transplant Recipients (SRTR) data, simulations extend over 2 years. With an initial pool of 400, respective candidate and NDD arrival rates of 2 per day and 3 per month, and delay times for access to DD-CIK of 6 months or less, including DD-CIKs increases the number of transplants by at least 447 over 2 years, and greatly reduces waiting times of KPDP candidates. Potential effects on waitlist candidates are discussed as are policy and ethical issues.

A Roadmap for Innovation to Advance Transplant Access and Outcomes: A Position Statement From the National Kidney Foundation.

Over the past 65 years, kidney transplantation has evolved into the optimal treatment for patients with kidney failure, dramatically reducing suffering through improved survival and quality of life. However, access to transplant is still limited by organ supply, opportunities for transplant are inequitably distributed, and lifelong transplant survival remains elusive. To address these persistent needs, the National Kidney Foundation convened an expert panel to define an agenda for future research. The key priorities identified by the panel center on the needs to develop and evaluate strategies to expand living donation, improve waitlist management and transplant readiness, maximize use of available deceased donor organs, and extend allograft longevity. Strategies targeting the critical goal of decreasing organ discard that warrant research investment include educating patients and clinicians about potential benefits of accepting nonstandard organs, use of novel organ assessment technologies and real-time decision support, and approaches to preserve and resuscitate allografts before implantation. The development of personalized strategies to reduce the burden of lifelong immunosuppression and support "one transplant for life" was also identified as a vital priority. The panel noted the specific goal of improving transplant access and graft survival for children with kidney failure. This ambitious agenda will focus research investment to promote greater equity and efficiency in access to transplantation, and help sustain long-term benefits of the gift of life for more patients in need.

Burden and Cost of Caring for US Veterans With CKD: Initial Findings From the VA Renal Information System (VA-REINS).

Kidney disease is a common, complex, costly, and life-limiting condition. Most kidney disease registries or information systems have been limited to single institutions or regions. A national US Department of Veterans Affairs (VA) Renal Information System (VA-REINS) was recently developed. We describe its creation and present key initial findings related to chronic kidney disease (CKD) without kidney replacement therapy (KRT). Data from the VA's Corporate Data Warehouse were processed and linked with national Medicare data for patients with CKD receiving KRT. Operational definitions for VA user, CKD, acute kidney injury, and kidney failure were developed. Among 7 million VA users in fiscal year 2014, CKD was identified using either a strict or liberal operational definition in 1.1 million (16.4%) and 2.5 million (36.3%) veterans, respectively. Most were identified using an estimated glomerular filtration rate laboratory phenotype, some through proteinuria assessment, and very few through International Classification of Diseases, Ninth Revision coding. The VA spent ∼$18 billion for the care of patients with CKD without KRT, most of which was for CKD stage 3, with higher per-patient costs by CKD stage. VA-REINS can be leveraged for disease surveillance, population health management, and improving the quality and value of care, thereby enhancing VA's capacity as a patient-centered learning health system for US veterans.

Life and expectations post-kidney transplant: a qualitative analysis of patient responses.

BACKGROUND: The effect of a kidney transplant on a recipient extends beyond the restoration of kidney function. However, there is limited qualitative analysis of recipient perspectives on life following transplantation, particularly in the United States. To understand the full patient experience, it is necessary to understand recipient views on life adjustments after kidney transplantation, medical management, and quality of life. This could lead to improvements in recipient care and sense of well-being. METHODS: We conducted a paper-based survey from March 23 to October 1, 2015 of 476 kidney transplant recipients at the University of Michigan Health System in Ann Arbor, Michigan. We analyzed their open-ended responses using qualitative research methods. This is a companion analysis to a previous quantitative report on the closed-ended responses to that survey. RESULTS: Common themes relating to changes following transplantation included: improvements in quality of life, a return to normalcy, better health and more energy. Concerns included: duration of graft survival, fears about one day returning to dialysis or needing to undergo another kidney transplant, comorbidities, future quality of life, and the cost and quality of their healthcare. Many recipients were grateful for their transplant, but some were anxious about the burdens transplantation placed on their loved ones. CONCLUSIONS: While most recipients reported meaningful improvements in health and lifestyle after kidney transplantation, a minority of participants experienced declines in energy or health status. Worries about how long the transplant will function, future health, and cost and quality of healthcare are prevalent. Future research could study the effects of providing additional information, programs, and interventions following transplantation that target these concerns. This may better prepare and support kidney recipients and lead to improvements in the patient experience.

The adoption of generic immunosuppressant medications in kidney, liver, and heart transplantation among recipients in Colorado or nationally with Medicare part D.

The transplant community is divided regarding whether substitution with generic immunosuppressants is appropriate for organ transplant recipients. We estimated the rate of uptake over time of generic immunosuppressants using US Medicare Part D Prescription Drug Event (PDE) and Colorado pharmacy claims (including both Part D and non-Part D) data from 2008 to 2013. Data from 26 070 kidney, 15 548 liver, and 6685 heart recipients from Part D, and 1138 kidney and 389 liver recipients from Colorado were analyzed. The proportions of patients with PDEs or claims for generic and brand-name tacrolimus or mycophenolate mofetil were calculated over time by transplanted organ and drug. Among Part D kidney, liver, and heart beneficiaries, the proportion dispensed generic tacrolimus reached 50%-56% at 1 year after first generic approval and 78%-81% by December 2013. The proportion dispensed generic mycophenolate mofetil reached 70%-73% at 1 year after generic market entry and 88%-90% by December 2013. There was wide interstate variability in generic uptake, with faster uptake in Colorado compared with most other states. Overall, generic substitution for tacrolimus and mycophenolate mofetil for organ transplant recipients increased rapidly following first availability, and utilization of generic immunosuppressants exceeded that of brand-name products within a year of market entry.

Coagulation status after therapeutic plasma exchange using citrate in kidney transplant recipients.

BACKGROUND: Therapeutic plasma exchange (TPE) is increasingly used for treatment of antibody-mediated rejection (AMR) after solid organ transplants. There is concern that TPE may increase risk of bleeding, although data are limited. After TPE, clot-based coagulation tests may not accurately represent the levels of coagulation factors due to the effect of citrate. We investigated protein levels of fibrinogen using antigen detection method (FibAg) and correlated results with a clot-based fibrinogen activity test (Fib). STUDY DESIGN AND METHODS: Nine kidney transplant recipients who received TPE for AMR were investigated. Fib, FibAg, prothrombin time/international normalized ratio (PT/INR), partial thromboplastin time (PTT), coagulation factor X chromogenic activity (CFX), and ionized calcium (iCa) were measured at pre- and post-TPE and 1, 3, 6, 9, 24, and 48 hours after the first TPE. RESULTS: Mean Fib/FibAg ratio before TPE was 1.08; therefore, all Fib values were normalized (n) by dividing by 1.08. Overall, the mean normalized Fib (nFib)/FibAg ratio at post-TPE was 0.89 and returned to close to 1.0 at 6 hours after the first TPE. Decreases in nFib, FibAg, and CFX and increases in PT/INR and PTT post-TPE were observed. The lowest Fib, FibAg, CFX, platelet, and iCa levels were still at levels that would be considered sufficient for hemostasis at all time points. CONCLUSION: The mean nFib/FibAg ratio after TPE was 0.89 and normalized in 6 hours, which demonstrates a persistent effect of citrate for up to 6 hours. Therefore, similar data observed in clot-based tests of PT/INR and PTT may be falsely elevated up to 6 hours after TPE due to the citrate effect.

Efficacy of plasmapheresis on donor-specific antibody reduction by HLA specificity in post-kidney transplant recipients.

BACKGROUND: Donor-specific antibodies (DSAs) to HLA antigens can cause acute antibody-mediated rejection (AMR) after kidney transplantation (Txp). Therapeutic plasma exchange (TPE) has been used for AMR treatment; however, DSA reduction rates are inconsistent. We investigated DSA reduction rates by HLA specificity and clinical outcome. STUDY DESIGN AND METHODS: Sixty-four courses of TPE for 56 kidney Txp recipients with high DSA were investigated. Dates of TPE procedures and Txp, patients' age, sex, race, creatinine (Cr), and mean fluorescent intensity (MFI) of DSA were retrieved. MFI reduction rate after one to three TPE and four to six TPE procedures were calculated by HLA DSA specificity in each patient, and the mean reduction rates were compared. The relationship of TPE treatment, MFI or Cr improvement rate, and graft age was also investigated. RESULTS: Patients received a mean 6.0 TPE procedures. Most received intravenous immunoglobulin after TPE and immunosuppressives. Forty-two cases (65.6%) had DSA to HLA Class I and 54 cases (84.4%) to Class II, including 32 cases (50.0%) to both. Mean MFI reduction rates after one to three TPE and four to six TPE procedures were 25.7 and 37.1% in HLA Class I, 25.1 and 34.2% in Class II, and 14.3 and 19.9% in DR51-53. The mean Cr improvements at the end of TPE and 3 and 6 months after TPE were 3.41, -0.37, and -0.72%, respectively. CONCLUSION: Six TPE procedures decreased DSA more than three TPE procedures, but reduction rate was lower by the second three TPE procedures than the first three TPE procedures. Although the mean Cr improvement was minimal, the treatment has good potential to stop further deterioration of kidney function. Better Cr improvement rate is correlated with the graft age.

The global diffusion of organ transplantation: trends, drivers and policy implications.

Rising incomes, the spread of personal insurance, lifestyle factors adding to the burden of illness, ageing populations, globalization and skills transfer within the medical community have increased worldwide demand for organ transplantation. The Global Observatory on Donation and Transplantation, which was built in response to World Health Assembly resolution WHA57.18, has conducted ongoing documentation of global transplantation activities since 2007. In this paper, we use the Global Observatory's data to describe the current distribution of - and trends in - transplantation activities and to evaluate the role of health systems factors and macroeconomics in the diffusion of transplantation technology. We then consider the implications of our results for health policies relating to organ donation and transplantation. Of the World Health Organization's Member States, most now engage in organ transplantation and more than a third performed deceased donor transplantation in 2011. In general, the Member States that engage in organ transplantation have greater access to physician services and greater total health spending per capita than the Member States where organ transplantation is not performed. The provision of deceased donor transplantation was closely associated with high levels of gross national income per capita. There are several ways in which governments can support the ethical development of organ donation and transplantation programmes. Specifically, they can ensure that appropriate legislation, regulation and oversight are in place, and monitor donation and transplantation activities, practices and outcomes. Moreover, they can allocate resources towards the training of specialist physicians, surgeons and transplant coordinators, and implement a professional donor-procurement network.

La hausse des revenus, le développement des assurances personnelles, les facteurs de mode de vie ajoutant à la charge de morbidité des maladies, le vieillissement des populations, la mondialisation et le transfert des compétences au sein de la communauté médicale ont augmenté la demande mondiale de transplantation d'organe. L'Observatoire Mondial du Don et de la Transplantation, qui a été fondé en réponse à la résolution WHA57.18 de l'Organisation mondiale de la Santé, a rassemblé une documentation sur les activités de transplantation dans le monde de façon continue depuis 2007. Dans cet article, nous utilisons les données de l'Observatoire Mondial pour décrire la distribution actuelle (et les tendances) des activités de transplantation et pour évaluer le rôle des facteurs de systèmes de santé et de la macroéconomie dans la diffusion des technologies de transplantation. Nous considérons ensuite les implications de nos résultats sur les politiques de santé relatives au don et à la transplantation d'organe. La majorité des États Membres de l'Organisation mondiale de la Santé s'engagent maintenant dans la transplantation d'organe et plus d'un tiers d'entre eux ont réalisé des transplantations avec des organes provenant de donneurs décédés en 2011. En général, les États Membres qui se sont engagés dans la transplantation d'organe, ont un meilleur accès aux services médicaux et des dépenses totales de santé plus élevées par habitant que les États Membres où la transplantation d'organe n'est pas réalisée. La disponibilité de la transplantation avec des organes provenant de donneurs décédés était étroitement associée avec des niveaux élevés de revenu national brut par habitant. Il existe plusieurs manières possibles pour les gouvernements de soutenir le développement éthique des programmes de don et de transplantation d'organe. En particulier, ils peuvent s'assurer que la législation, la réglementation et la surveillance sont en place, et contrôler les activités, les pratiques et les résultats des dons et des transplantations. En outre, ils peuvent affecter des ressources pour la formation des médecins spécialistes, des chirurgiens et des coordinateurs de transplantation, et mettre en œuvre un réseau professionnel de recrutement des donneurs.

El aumento de la renta, la proliferación de los seguros personales y los factores del estilo de vida, sumados a la carga de enfermedades, el envejecimiento de la población, la globalización y la transferencia de conocimientos en la comunidad médica, han aumentado la demanda mundial de trasplantes de órganos. El Observatorio Mundial de Donación y Trasplante, creado en respuesta a la resolución WHA57.18 de la Asamblea Mundial de la Salud, ha llevado a cabo una documentación continua de las actividades mundiales de trasplantes desde 2007. En este informe, se emplean los datos del Observatorio Global para describir la distribución actual (y las tendencias) de las actividades de trasplante y para evaluar el papel de los factores de los sistemas sanitarios y de la macroeconomía en la difusión de la tecnología de trasplante. A continuación, se consideraron las repercusiones de los resultados en las políticas de salud relacionadas con la donación y el trasplante de órganos. En la actualidad, la mayoría de los Estados miembros de la Organización Mundial de la Salud participa en el trasplante de órganos y más de un tercio realizó trasplantes de donantes fallecidos en 2011. En general, los Estados miembros que participan en el trasplante de órganos cuentan con mayor acceso a los servicios médicos y tienen un mayor gasto total en salud per cápita que los Estados miembros donde no se realizan el trasplantes de órganos. La prestación de los trasplantes de donantes fallecidos se asoció estrechamente con altos niveles de renta nacional bruta per cápita. Existen varias formas en que los gobiernos pueden fomentar el desarrollo ético de los programas de donación y trasplante de órganos. En concreto, pueden garantizar que se adopte una legislación, regulación y supervisión adecuadas, así como realizar un seguimiento de las actividades, las prácticas y los resultados de la donación y el trasplante. Además, pueden destinar recursos a la formación de médicos especialistas, cirujanos y coordinadores de trasplantes, así como poner en marcha una red profesional de adquisición de donantes.

Decision Making in Kidney Paired Donation Programs with Altruistic Donors.

In recent years, kidney paired donation (KPD) has been extended to include living non-directed or altruistic donors, in which an altruistic donor donates to the candidate of an incompatible donor-candidate pair with the understanding that the donor in that pair will further donate to the candidate of a second pair, and so on; such a process continues and thus forms an altruistic donor-initiated chain. In this paper, we propose a novel strategy to sequentially allocate the altruistic donor (or bridge donor) so as to maximize the expected utility; analogous to the way a computer plays chess, the idea is to evaluate different allocations for each altruistic donor (or bridge donor) by looking several moves ahead in a derived look-ahead search tree. Simulation studies are provided to illustrate and evaluate our proposed method.

Comparison of communication and personal characteristics of living kidney donors and a matched quota sample.

Deceased organ donation does not meet the need for kidney transplants. Thus, it is important to examine topics relevant to kidney donors such as communication leading to the donation decision and donor characteristics. This study reports personal characteristics and communication leading to the decision to donate among living kidney donors and a demographically matched quota sample. Donors had higher scores for compassion, while non-donors reported more volunteerism. Donors and non-donors did not differ in conversation or conformity orientations of family communication styles. Only 4.7% of donors reported being asked to donate directly. Matched respondents reported feeling more comfortable than unsettled with the idea of being asked directly and indicated a preference to learn of the need directly or indirectly, giving them the option to volunteer. The majority of donors were giving to family members and friends, and the matched sample indicated greater willingness to donate to immediate family members, followed by friends. Practical implications of the findings are offered.

Kidney Paired Donation Chains Initiated by Deceased Donors.

Introduction: Rather than generating 1 transplant by directly donating to a candidate on the waitlist, deceased donors (DDs) could achieve additional transplants by donating to a candidate in a kidney paired donation (KPD) pool, thereby, initiating a chain that ends with a living donor (LD) donating to a candidate on the waitlist. We model outcomes arising from various strategies that allow DDs to initiate KPD chains. Methods: We base simulations on actual 2016 to 2017 US DD and waitlist data and use simulated KPD pools to model DD-initiated KPD chains. We also consider methods to assess and overcome the primary criticism of this approach, namely the potential to disadvantage blood type O-waitlisted candidates. Results: Compared with shorter DD-initiated KPD chains, longer chains increase the number of KPD transplants by up to 5% and reduce the number of DDs allocated to the KPD pool by 25%. These strategies increase the overall number of blood type O transplants and make LDs available to candidates on the waitlist. Restricting allocation of blood type O DDs to require ending KPD chains with LD blood type O donations to the waitlist markedly reduces the number of KPD transplants achieved. Conclusion: Allocating fewer than 3% of DD to initiate KPD chains could increase the number of kidney transplants by up to 290 annually. Such use of DDs allows additional transplantation of highly sensitized and blood type O KPD candidates. Collectively, patients of each blood type, including blood type O, would benefit from the proposed strategies.

Living kidney donor follow-up: state-of-the-art and future directions, conference summary and recommendations.

In light of continued uncertainty regarding postkidney donation medical, psychosocial and socioeconomic outcomes for traditional living donors and especially for donors meeting more relaxed acceptance criteria, a meeting was held in September 2010 to (1) review limitations of existing data on outcomes of living kidney donors; (2) assess and define the need for long-term follow-up of living kidney donors; (3) identify the potential system requirements, infrastructure and costs of long-term follow-up for living kidney donor outcomes in the United States and (4) explore practical options for future development and funding of United States living kidney donor data collection, metrics and endpoints. Conference participants included prior kidney donors, physicians, surgeons, medical ethicists, social scientists, donor coordinators, social workers, independent donor advocates and representatives of payer organizations and the federal government. The findings and recommendations generated at this meeting are presented.

Living kidney donor decision making and communication.

There is high demand for kidney donors in the United States, and it is widely accepted that living donation is optimal for individuals who need a kidney. Much research has focused on the potential recipient, but little has been studied about the communication and decision making of living kidney donors. Interviews assessed the communication and decision-making processes of 43 kidney donor volunteers. Almost all of the participants were not asked, but instead volunteered, to donate. The majority of donors reported having conversations with the recipient and speaking about their decisions with other individuals in their social networks besides the recipient. Some participants said that they stopped talking to others because of negative feedback. Future research should further examine the communication of donors with non-recipient others and potential methods of training recipients and donors to communicate effectively about the donation process.

KPDGUI: An interactive application for optimization and management of a virtual kidney paired donation program.

BACKGROUND AND OBJECTIVES: The aim in kidney paired donation (KPD) is typically to maximize the number of transplants achieved through the exchange of donors in a pool comprising incompatible donor-candidate pairs and non-directed (or altruistic) donors. With many possible options in a KPD pool at any given time, the most appropriate set of exchanges cannot be determined by simple inspection. In practice, computer algorithms are used to determine the optimal set of exchanges to pursue. Here, we present our software application, KPDGUI (Kidney Paired Donation Graphical User Interface), for management and optimization of KPD programs. METHODS: While proprietary software platforms for managing KPD programs exist to provide solutions to the standard KPD problem, our application implements newly investigated optimization criteria that account for uncertainty regarding the viability of selected transplants and arrange for fallback options in cases where potential exchanges cannot proceed, with intuitive resources for visualizing alternative optimization solutions. RESULTS: We illustrate the advantage of accounting for uncertainty and arranging for fallback options in KPD using our application through a case study involving real data from a paired donation program, comparing solutions produced under different optimization criteria and algorithmic priorities. CONCLUSIONS: KPDGUI is a flexible and powerful tool for offering decision support to clinicians and researchers on possible KPD transplant options to pursue under different user-specified optimization schemes.

Secular Trends in the Cost of Immunosuppressants after Solid Organ Transplantation in the United States.

BACKGROUND AND OBJECTIVES: Immunosuppressive medications are critical for maintenance of graft function in transplant recipients but can represent a substantial financial burden to patients and their insurance carriers. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: To determine whether availability of generic immunosuppressive medications starting in 2009 may have alleviated some of that burden, we used Medicare Part D prescription drug events between 2008 and 2013 to estimate the average annualized per-patient payments made by patients and Medicare in a large national sample of kidney, liver, and heart transplant recipients. Repeated measures linear regression was used to determine changes in payments over the study period. RESULTS: Medicare Part D payments for two commonly used immunosuppressive medications, tacrolimus and mycophenolic acid (including mycophenolate mofetil and mycophenolate sodium), decreased overall by 48%-67% across organs and drugs from 2008 to 2013, reflecting decreasing payments for brand and generic tacrolimus (21%-54%), and generic mycophenolate (72%-74%). Low-income subsidy payments, which are additional payments made under Medicare Part D, also decreased during the study period. Out-of-pocket payments by patients who did not receive the low-income subsidy decreased by more than those who did receive the low-income subsidy (63%-79% versus 24%-44%). CONCLUSIONS: The decline in payments by Medicare Part D and by transplant recipients for tacrolimus and mycophenolate between 2008 and 2013 suggests that the introduction of generic immunosuppressants during this period has resulted in substantial cost savings to Medicare and to patients, largely reflecting the transition from brand to generic products.

Comparison of patient and provider goals, expectations, and experiences following kidney transplantation.

OBJECTIVE: This study examined whether kidney transplant recipients' post-transplant goals and expectations align with those as perceived by their healthcare providers. METHODS: Post-transplant goals and expectations across four domains were assessed via a descriptive survey of healthcare providers (N=72) and kidney transplant recipients (N=476) at the University of Michigan from March 23 - October 1, 2015. Demographic and transplant-related data were collected via a retrospective review of medical records, and survey responses were compared using Chi-square tests, Wilcoxon two-sample tests, and logistic regression. RESULTS: Patients expressed higher quality of life (mean Neuro-QOL T-score 60.2 vs. 52.7), were less likely to report that they were currently experiencing complications (11% vs. 24%), and anticipated their transplants to last longer (median 25 vs. 15 years) and to live longer (median 80 vs. 71 years) than providers expected for their typical patient. However, provider perceptions of patients' future ability to feel well, perform daily activities and work were significantly higher than those expressed by patients (all p<0.05). CONCLUSION: Kidney transplant patient and provider expectations differ in significant ways. PRACTICE IMPLICATIONS: Identified areas of discordance may provide opportunities for patients and providers to better evaluate treatment option tradeoffs in post-transplant clinical interactions.

Establishing a Core Outcome Measure for Life Participation: A Standardized Outcomes in Nephrology-kidney Transplantation Consensus Workshop Report.

BACKGROUND: Kidney transplantation confers substantial survival and quality of life benefits for many patients with end-stage kidney disease compared with dialysis, but complications and side effects of immunosuppression can impair participation in daily life activities. Life participation is a critically important patient-reported outcome for kidney transplant recipients but is infrequently and inconsistently measured in trials. We convened a consensus workshop on establishing an outcome measure for life participation for use in all trials in kidney transplantation. METHODS: Twenty-five (43%) kidney transplant recipients/caregivers and 33 (57%) health professionals from 8 countries participated in 6 facilitated breakout group discussions. Transcripts were analyzed thematically. RESULTS: Four themes were identified. Returning to normality conveyed the patients' goals to fulfill their roles (ie, in their family, work, and community) and reestablish a normal lifestyle after transplant. Recognizing the diverse meaning and activities of "life" explicitly acknowledged life participation as a subjective concept that could refer to different activities (eg, employment, recreation, family duties) for each individual patient. Capturing vulnerability and fluctuations posttransplant (eg, due to complications and side-effects) distinguished between experiences in the first year posttransplant and the long-term impact of transplantation. Having a scientifically rigorous, feasible, and meaningful measure was expected to enable consistent and frequent assessment of life participation in trials in kidney transplantation. CONCLUSIONS: A feasible and validated core outcome measure for life participation is needed so that this critically important patient-reported outcome can be consistently and meaningfully assessed in trials in kidney transplantation to inform decision making and care of recipients.