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1.  Order of Donor Type in Pediatric Kidney Transplant Recipients Requiring Retransplantation 
Transplantation  2013;96(5):487-493.
Background
Living donor kidney transplantation (KT) is encouraged for children with end-stage renal disease due to superior long-term graft survival compared with deceased donor KT. Despite this, there has been a steady decrease in the use of living donor KT for pediatric recipients. Due to their young age at transplant, most pediatric recipients eventually require retransplantation, and the optimal order of donor type is not clear.
Methods
Using the Scientific Registry of Transplant Recipients, we analyzed first and second graft survival among 14,799 pediatric (<18 years old) recipients undergoing KT between 1987–2010.
Results
Living donor grafts had longer survival compared to deceased donor grafts, similarly among both first (adjusted hazard ratio [aHR]=0.78, 95% CI: 0.73–0.84; p<0.001) and second (aHR=0.74, 95% CI: 0.64–0.84; p<0.001) transplants. Living donor second grafts had longer survival compared to deceased donor second grafts, similarly following living donor (aHR=0.68, 95% CI: 0.56–0.83; p<0.001) and deceased donor (aHR=0.77, 95% CI: 0.63–0.95; p=0.02) first transplants. Cumulative graft life of two transplants was similar regardless of the order of deceased donor and living donor transplantation.
Conclusions
Deceased donor KT in pediatric recipients followed by living donor retransplantation does not negatively impact the living donor graft survival advantage and provides similar cumulative graft life compared to living donor KT followed by deceased donor retransplantation. Clinical decision-making for pediatric patients with healthy, willing living donors should consider these findings in addition to the risk of sensitization, aging of the living donor, and deceased donor waiting times.
doi:10.1097/TP.0b013e31829acb10
PMCID: PMC3763240  PMID: 24002689
pediatric kidney transplantation; donor selection; graft survival; donor type; retransplantation
2.  Prospective Swiss cohort study of living-kidney donors: study protocol 
BMJ Open  2011;1(2):e000202.
Background
Offering living kidney donation raised the concern that donors are exposed to unknown risks. All Swiss transplant centres therefore decided to start a prospective cohort study of living kidney donors in Switzerland. This paper describes the rationale for and implementation of this cohort study.
Methods/design
All kidney donors in Switzerland are registered and examined before donation and biennially after donation starting in the first year after nephrectomy. Before each follow-up visit, the study centre sends a package to the kidney donor containing the health questionnaire, blood and urine tubes and a prepaid envelope for sending the samples to the central laboratory. The donor makes an appointment with their family physician, who examines the donor and reports findings such as pain and other complaints, blood pressure, creatinine, albumin, all major health events and the state of mental and social well-being to the study centre. The family doctor draws the blood sample and mails it with the urine sample in the prepaid envelope. All data are centrally managed. All abnormal findings in the follow-up of individual donors are regularly discussed with the principal investigator, and necessary clinical changes made and recorded in the database. The health insurance of the recipient covers all costs of the donor follow-up. The main outcomes are the occurrence of albuminuria, hypertension and renal insufficiency. The secondary outcomes are major somatic and social events such as death, cardiovascular disease, stroke and depression.
Discussion
This prospective cohort offers unique opportunities to assess the risks of living kidney donation and will allow us to examine the risks associated with the methods used for nephrectomy in Switzerland (various forms of open surgery and laparoscopic nephrectomy). The prospective collection of all clinically relevant data and the regular monitoring of donors will allow timely interventions at early stages before serious kidney and general health problems occur.
Article summary
Article focus
To describe the rationale and set-up of the Swiss Living Kidney Donor Cohort Study.
Key messages
The question of whether kidney donation increases health risks such as hypertension and renal failure is still unsettled.
Data for this countrywide prospective cohort study over the period of at least 18 years will answer many still open questions concerning living kidney donor outcome.
Strengths and limitations of this study
This countrywide cohort study includes all consenting Swiss living kidney donors.
This is a long-term follow-up allowing the assessment of clinically relevant outcomes of donation such as hypertension and renal failure.
We cannot completely rule out residual confounding in this observational study.
doi:10.1136/bmjopen-2011-000202
PMCID: PMC3208897  PMID: 22080536
3.  Marginal kidney donor 
Renal transplantation is the treatment of choice for a medically eligible patient with end stage renal disease. The number of renal transplants has increased rapidly over the last two decades. However, the demand for organs has increased even more. This disparity between the availability of organs and waitlisted patients for transplants has forced many transplant centers across the world to use marginal kidneys and donors. We performed a Medline search to establish the current status of marginal kidney donors in the world. Transplant programs using marginal deceased renal grafts is well established. The focus is now on efforts to improve their results. Utilization of non-heart-beating donors is still in a plateau phase and comprises a minor percentage of deceased donations. The main concern is primary non-function of the renal graft apart from legal and ethical issues. Transplants with living donors outnumbered cadaveric transplants at many centers in the last decade. There has been an increased use of marginal living kidney donors with some acceptable medical risks. Our primary concern is the safety of the living donor. There is not enough scientific data available to quantify the risks involved for such donation. The definition of marginal living donor is still not clear and there are no uniform recommendations. The decision must be tailored to each donor who in turn should be actively involved at all levels of the decision-making process. In the current circumstances, our responsibility is very crucial in making decisions for either accepting or rejecting a marginal living donor.
doi:10.4103/0970-1591.33726
PMCID: PMC2721608  PMID: 19718332
Complex living donor; deceased marginal donor; marginal kidney donor; non-heart-beating donor
4.  Religious attitudes towards living kidney donation among Dutch renal patients 
Terminal kidney patients are faced with lower quality of life, restricted diets and higher morbidity and mortality rates while waiting for deceased donor kidney transplantation. Fortunately, living kidney donation has proven to be a better treatment alternative (e.g. in terms of waiting time and graft survival rates). We observed an inequality in the number of living kidney transplantations performed between the non-European and the European patients in our center. Such inequality has been also observed elsewhere in this field and it has been suggested that this inequality relates to, among other things, attitude differences towards donation based on religious beliefs. In this qualitative research we investigated whether religion might indeed (partly) be the explanation of the inequalities in living donor kidney transplants (LDKT) among non-European patients. Fifty patients participated in focus group discussions and in-depth interviews. The interviews were conducted following the focus group method and analyzed in line with Grounded Theory. The qualitative data analyses were performed in Atlas.ti. We found that religion is not perceived as an obstacle to living donation and that religion actually promotes helping and saving the life of a person. Issues such as integrity of the body were not seen as barriers to LDKT. We observed also that there are still uncertainties and a lack of awareness about the position of religion regarding living organ donation within communities, confusion due to varying interpretations of Holy Scriptures and misconceptions regarding the process of donation. Faith leaders play an important educational role and their opinion is influential. This study has identified modifiable factors which may contribute to the ethnic disparity in our living donation program. We argue that we need to strive for more clarity and awareness regarding the stance of religion on the issue of living donation in the local community. Faith leaders could be key figures in increasing awareness and alleviating uncertainty regarding living donation and transplantation.
doi:10.1007/s11019-011-9326-z
PMCID: PMC3319887  PMID: 21512856
Attitudes; Communication; Ethnicity; Kidney transplantation; Organ donation; Religion
5.  Perception About Transplant of Rural and Urban Patients With Chronic Kidney Disease; A Qualitative Study 
Nephro-urology Monthly  2014;6(2):e15726.
Background:
Chronic kidney disease (CKD) is a worldwide public health problem with increasing incidence and prevalence and associated expenses.
Objectives:
To explore different perceptions of rural and urban patients with chronic kidney disease (CKD) about kidney transplant.
Patients and Methods:
We conducted four focus groups, each including 5 or 6 patients with stage 5 CKD or end stage renal disease living in a rural or urban area. Open-ended questions probed patient familiarity with kidney transplant, perceptions of benefits of kidney transplant, perceived barriers to kidney transplant, and views about living donation. All the sessions were recorded and professionally transcribed. Responses were pooled, de-identified, and analyzed using qualitative thematic content analysis.
Results:
Urban patients were more likely to receive supplementary information and being strongly encouraged by their nephrologists to seek transplant. All participants acknowledged “independence” as the main advantage of transplantation. Increased freedom to travel and improved life expectancy were mentioned only among the urban groups. The main themes in all groups regarding perceived barriers to transplant were the tedious pre-transplant testing and workup expenses. Among rural groups, there was a perception that distance from transplant centers impedes transplant evaluation. Religious reasons favoring and opposing transplant were mentioned by participants in a rural group. Some members contended that since illness is God’s will, we should not change it. Others in the same group argued that “God is not ready for us to give up”. Praise and gratitude for the living donor were expressed in all groups, but concerns about donor’s outcome were discussed only within the rural groups. In discussing preference about known or anonymous donors, members of an urban group mentioned favoring an anonymous donor, citing unease with a sense of life-long indebtedness.
Conclusions:
Observed differences in perceptions among rural and urban patients about aspects of transplant may contribute to geographic disparities in transplant. The findings could be helpful to guide future individualized, culturally sensitive educational interventions about transplant for patients with CKD.
doi:10.5812/numonthly.15726
PMCID: PMC3997949  PMID: 24783174
Focus Groups; Geography; Disparity
6.  Changing Pattern of Organ Donation and Utilization in the USA 
Background: Organ transplantation has proven highly effective in the treatment of various forms of end-stage organ failure. However, organ shortage is still the greatest challenge facing the field of organ transplantation.
Objective: To assess the pattern of organ donation and utilization during the past decade in the USA.
Methods: We studied OPTN/UNOS database for organ donation between January 2000 and December 2009. The retrieved records were then categorized into two time periods—from January 2000 to December 2004 (era 1), and from January 2005 to December 2009 (era 2).
Results: There were 65,802 living and 71,401 deceased donors in the US from 2000 to 2009, including 66,518 (93.2%) brain-dead donors and 4,883 (6.8%) donation after cardiac death. Comparing two periods—from January 2000 to December 2004 (era 1) and from January 2005 to December 2009 (era 2), the number of deceased donors increased by 25% from 31,692 to 39,709 and living donors decreased by 7.6%. Donation after cardiac death increased from 3.5% to 9.3%. The portion of donors older than 64 years increased from 6.9% in era 1 to 11.3% in era 2 (p=0.03). The number of donors with a body mass index of >35 kg/m2 was also increased from 6.8% to 11.2%. A significant increase in the incidence of cardiovascular/cerebrovascular as cause of death was also noted from 38.1% in era 1 to 56.1% in era 2 (p<0.001), as was a corresponding decrease in the incidence of death due to head trauma (34.9% vs. 48.8%). The overall discard rate also increased by 41% from 13,411 in era 1 to 19,516 in era 2. This increase in discards was especially more prominent in donation after cardiac death group which rose by 374% from 440 in era 1 to 2,089 in era 2. The discard rate for livers and kidneys increased by 31% and 68%, respectively, comparing era 1 and era 2. We noted a 78% increase for discarded donation after cardiac death livers and 1,210% for discarded donation after cardiac death kidneys.
Conclusion: We detected significant changes in the make-up of the donor pool over the past decade in the US. Over time, donor characteristics have changed with increased numbers of elderly donors and donors with comorbidities, especially donors who died of cardiovascular/cerebrovascular disease. The incidence of donation after cardiac death has increased significantly; brain-dead donors have only increased slightly and living donors have decreased. As the result, the discard rates have increased. The transplant community and policy makers should consider every precaution to safeguard the donor pool and prevent the decay of organ quality in favor of quantity.
PMCID: PMC4089300  PMID: 25013640
Organ transplantation; End-stage organ failure; Brain-dead donor; Living donors
7.  Who should be prioritized for renal transplantation?: Analysis of key stakeholder preferences using discrete choice experiments 
BMC Nephrology  2012;13:152.
Background
Policies for allocating deceased donor kidneys have recently shifted from allocation based on Human Leucocyte Antigen (HLA) tissue matching in the UK and USA. Newer allocation algorithms incorporate waiting time as a primary factor, and in the UK, young adults are also favoured. However, there is little contemporary UK research on the views of stakeholders in the transplant process to inform future allocation policy. This research project aimed to address this issue.
Methods
Discrete Choice Experiment (DCE) questionnaires were used to establish priorities for kidney transplantation among different stakeholder groups in the UK. Questionnaires were targeted at patients, carers, donors / relatives of deceased donors, and healthcare professionals. Attributes considered included: waiting time; donor-recipient HLA match; whether a recipient had dependents; diseases affecting life expectancy; and diseases affecting quality of life.
Results
Responses were obtained from 908 patients (including 98 ethnic minorities); 41 carers; 48 donors / relatives of deceased donors; and 113 healthcare professionals. The patient group demonstrated statistically different preferences for every attribute (i.e. significantly different from zero) so implying that changes in given attributes affected preferences, except when prioritizing those with no rather than moderate diseases affecting quality of life. The attributes valued highly related to waiting time, tissue match, prioritizing those with dependents, and prioritizing those with moderate rather than severe diseases affecting life expectancy. Some preferences differed between healthcare professionals and patients, and ethnic minority and non-ethnic minority patients. Only non-ethnic minority patients and healthcare professionals clearly prioritized those with better tissue matches.
Conclusions
Our econometric results are broadly supportive of the 2006 shift in UK transplant policy which emphasized prioritizing the young and long waiters. However, our findings suggest the need for a further review in the light of observed differences in preferences amongst ethnic minorities, and also because those with dependents may be a further priority.
doi:10.1186/1471-2369-13-152
PMCID: PMC3576250  PMID: 23173887
Renal transplant; Allocation; Choice experiment; Stakeholder
8.  Could living unrelated renal transplantation ameliorate the actual shortage of organs in the Balkan region? 
Hippokratia  2013;17(3):243-245.
Background: Despite the efforts for more transplants performed with organs from deceased donors, the living renal transplantation is still the predominant transplant activity in the Balkan region. In order to adress the severe organ shortage, we started accepting unrelated (emotionally related) living donors (LURD). Here we present our 10-year experience with living unrelated renal transplantation (LURT).
Methods: Twenty four LURT were performed in our center in the last 10 years. The mean recipients and donors age was 41.7 and 47.2 years, respectively. As LURD spouses (n=17) and extended family members (n=7) were accepted predominantly. All donors went through careful psychological evaluation in order to confirm emotional relationship. The final decision was taken after both the recipient and the donor signed a consent in front of a judge. A quadruple sequential immunosuppressive protocol was used in all recipients. The 5-year Kaplan Meier graft survival rate, HLA mismatch, rejection episodes, delayed graft function, serum creatinine and Glomerular filtration rate-Modification of the diet in renal disease (GFR-MDRD) were analyzed. The results were compared with 30 living related renal transplants (LRT) performed during the same time with mean recipients and donors age of 35.9 and 58.5 years, respectively.
Results: The mean follow up for LURT and LRT recipients were 81.4 and 79.6 months, respectively. There was a significant difference regarding recipients and donors age, HLA mismatch (5.07 and 2.9) and rejection episodes (16% vs. 11%) in LURT and LRT recipients. The 5 years graft survival rate was excellent in both groups (83 and 81%, respectively). There was no significant difference in 5 years serum creatinine (129.3 vs 121.1 μmol/lit) and 5 years GFR-MDRD (56.6 and 58.6 ml/min).
Conclusion: The authors present an excellent 5-year graft survival rate in both LURT and LRT recipients. Therefore, LURT could ameliorate the severe organ shortage in the region and could be recommended as a valuable source of organs in the countries with developed and underdeveloped deceased donor donation.
PMCID: PMC3872461  PMID: 24470735
Kidney unrelated transplantation; Kaplan-Meier surviving curves; glomerular filtration rate
9.  Day-of-surgery rejection of donors in living donor liver transplantation 
World Journal of Hepatology  2012;4(11):299-304.
AIM: To study diagnostic laparoscopy as a tool for excluding donors on the day of surgery in living donor liver transplantation (LDLT).
METHODS: This study analyzed prospectively collected data from all potential donors for LDLT. All of the donors were subjected to a three-step donor evaluation protocol at our institution. Step one consisted of a clinical and social evaluation, including a liver profile, hepatitis markers, a renal profile, a complete blood count, and an abdominal ultrasound with Doppler. Step two involved tests to exclude liver diseases and to evaluate the donor’s serological status. This step also included a radiological evaluation of the biliary anatomy and liver vascular anatomy using magnetic resonance cholangiopancreatography and a computed tomography (CT) angiogram, respectively. A CT volumetric study was used to calculate the volume of the liver parenchyma. Step three included an ultrasound-guided liver biopsy. Between November 2002 and May 2009, sixty-nine potential living donors were assessed by open exploration prior to harvesting the planned part of the liver. Between the end of May 2009 and October 2010, 30 potential living donors were assessed laparoscopically to determine whether to proceed with the abdominal incision to harvest part of the liver for donation.
RESULTS: Ninety-nine living donor liver transplants were attempted at our center between November 2002 and October 2010. Twelve of these procedures were aborted on the day of surgery (12.1%) due to donor findings, and eighty-seven were completed (87.9%). These 87 liver transplants were divided into the following groups: Group A, which included 65 transplants that were performed between November 2002 and May 2009, and Group B, which included 22 transplants that were performed between the end of May 2009 and October 2010. The demographic data for the two groups of donors were found to match; moreover, no significant difference was observed between the two groups of donors with respect to hospital stay, narcotic and non-narcotic analgesia requirements or the incidence of complications. Regarding the recipients, our study clearly revealed that there was no significant difference in either the incidence of different complications or the incidence of retransplantation between the two groups. Day-of-surgery donor assessment for LDLT procedures at our center has passed through two eras, open and laparoscopic. In the first era, sixty-nine LDLT procedures were attempted between November 2002 and May 2009. Upon open exploration of the donors on the day of surgery, sixty-five donors were found to have livers with a grossly normal appearance. Four donors out of 69 (5.7%) were rejected on the day of surgery because their livers were grossly fatty and pale. In the laparoscopic era, thirty LDLT procedures were attempted between the end of May 2009 and October 2010. After the laparoscopic assessment on the day of surgery, twenty-two transplantation procedures were completed (73.4%), and eight were aborted (26.6%). Our data showed that the levels of steatosis in the rejected donors were in the acceptable range. Moreover, the results of the liver biopsies of rejected donors were comparable between the group A and group B donors. The laparoscopic assessment of donors presents many advantages relative to the assessment of donors through open exploration; in particular, the laparoscopic assessment causes less pain, requires a shorter hospital stay and leads to far superior cosmetic results.
CONCLUSION: The laparoscopic assessment of donors in LDLT is a safe and acceptable procedure that avoids unnecessary large abdominal incisions and increases the chance of achieving donor safety.
doi:10.4254/wjh.v4.i11.299
PMCID: PMC3536836  PMID: 23293715
Live donor; Laparoscopic assessment; Rejected donors; Day of surgery; Fatty liver
10.  Legal and ethical aspects of organ donation and transplantation 
The legislation called the Transplantation of Human Organ Act (THO) was passed in India in 1994 to streamline organ donation and transplantation activities. Broadly, the act accepted brain death as a form of death and made the sale of organs a punishable offence. With the acceptance of brain death, it became possible to not only undertake kidney transplantations but also start other solid organ transplants like liver, heart, lungs, and pancreas. Despite the THO legislation, organ commerce and kidney scandals are regularly reported in the Indian media. In most instances, the implementation of the law has been flawed and more often than once its provisions have been abused. Parallel to the living related and unrelated donation program, the deceased donation program has slowly evolved in a few states. In approximately one-third of all liver transplants, the organs have come from the deceased donor program as have all the hearts and pancreas transplants. In these states, a few hospitals along with committed NGOs have kept the momentum of the deceased donor program. The MOHAN Foundation (NGO based in Tamil Nadu and Andhra Pradesh) has facilitated 400 of the 1,300 deceased organ transplants performed in the country over the last 14 years. To overcome organ shortage, developed countries are re-looking at the ethics of unrelated programs and there seems to be a move towards making this an acceptable legal alternative. The supply of deceased donors in these countries has peaked and there has been no further increase over the last few years. India is currently having a deceased donation rate of 0.05 to 0.08 per million population. We need to find a solution on how we can utilize the potentially large pool of trauma-related brain deaths for organ donation. This year in the state of Tamil Nadu, the Government has passed seven special orders. These orders are expected to streamline the activity of deceased donors and help increase their numbers. Recently, on July 30, 2008, the Government brought in a few new amendments as a Gazette with the purpose of putting a stop to organ commerce. The ethics of commerce in organ donation and transplant tourism has been widely criticized by international bodies. The legal and ethical principles that we follow universally with organ donation and transplantation are also important for the future as these may be used to resolve our conflicts related to emerging sciences such as cloning, tissue engineering, and stem cells.
doi:10.4103/0970-1591.56203
PMCID: PMC2779960  PMID: 19881131
Cadaver transplantation; ethics in transplantation; related donor
11.  Does Kidney Transplantation With Deceased or Living Donor Affect Graft Survival? 
Nephro-urology Monthly  2014;6(4):e12182.
Background:
There are growing numbers of patients with end-stage renal disease globally at an unexpected rate. Today, the most serious challenge in transplantation is organ shortage; hence, using deceased donor is increasingly encouraged.
Objectives:
The aim of the study was to investigate the differences in survival rates between kidney transplant recipients with deceased donor and living donor.
Patients and Methods:
In a retrospective cohort study, 218 patients who had undergone kidney transplantation in our institute from April 2008 to September 2010 were recruited. Demographics and post-transplantation follow-up data including immunosuppression regimens, rejection episodes, and survival rates were evaluated. The patients were assigned to two groups according to the donor kidney transplantation: group I, living donor kidney transplants; and group II, deceased donor kidney transplants.
Results:
Although there were no significant differences in one-year survival rates of patient and graft between study groups, three-years survival rates of patient and graft were significantly longer in living donor kidney transplants in comparison with the deceased donor kidney recipients (P = 0.006 and P = 0.004, respectively). In Cox-regression model after adjusting for other confounding factors such as age, sex, diabetes mellitus, and first- or second-time transplantation, overall patient and graft survivals were also significantly shorter in deceased kidney transplantation than those who received kidney from a living donor (HR, 3.5; 95% CI, 1.2-10.4; and P = 0.02 for patient survival; and HR, 5.4; 95% CI, 1.5-19.5; and P = 0.009 for graft survival).
Conclusions:
We found acceptable short-term survival in both groups; however, living donor recipients continue to have better long-term patient and graft survival rates.
doi:10.5812/numonthly.12182
PMCID: PMC4317718
Living Donor; Donor; Survival; Kidney Transplantations
12.  Ethical guidelines for the evaluation of living organ donors 
Canadian Journal of Surgery  2004;47(6):408-413.
Transplantation is an effective, life-prolonging treatment for organ failure. Demand has steadily increased over the past decade, creating a shortage in the supply of organs. In addition, the number of deceased organ donors has reached a plateau.
Living-donor transplantation is increasingly an option, influenced by favourable clinical outcomes and increased waiting times at most transplant centres across North America. Living-donor kidney transplants have exceeded deceased-donor transplant rates at some centres.
Organ donations from living donors have challenged transplant programs to develop a framework for determining donor acceptability. After a multidisciplinary consensus-building process of discussion and debate, the Multi-Organ Transplant Program of the University Health Network in Toronto has developed ethical guidelines for these procedures. These proposed guidelines address ethical concerns related to selection criteria and procedures, voluntariness, informed consent and disclosure of risks and benefits to both donor and recipient.
PMCID: PMC3211588  PMID: 15646438
13.  Changing Donor Source Pattern for Kidney Transplantation over 40 Years: A Single-Center Experience 
Background/Aims
Kidney transplantations at our center rely mainly on living donors. The purpose of this study was to suggest future donor supply directions by reviewing changing trends in donor type.
Methods
During the past 40 years, 1,690 kidney transplantations were performed at our center. We divided the follow-up period into four decades and the donor population into three groups: living related, living unrelated, and deceased. We analyzed changing trends in donors from each group for each decade. Patients receiving overseas transplantation were also included.
Results
The proportion of living related donors decreased from 84% (54/64) in the 1970s to 61% (281/458) in the 2000s. Living unrelated donors showed a sustained proportion of around 20% after 1990. However, among living unrelated donors, the proportion of spouse donors increased from 4.6% (17/369) in the 1980s to 8.5% (39/458) in the 2000s. Transplants from deceased donors were only 3.3% (12/369) in the 1980s. However the proportion of deceased donors increased gradually, reaching 13.2% (105/799) in the 1990s and 19.9% (91/458) after 2000. Overseas transplantations increased after 2000 and reached 20% of all cases treated in our center during the 2000s. Such transplantations peaked in 2006 and decreased markedly thereafter.
Conclusions
The proportion of each donor type has continuously changed, and the changes were associated with changes in the social structure and system. We expect that this study could be an important reference for other countries to estimate future changes of donor type.
doi:10.3904/kjim.2010.25.3.288
PMCID: PMC2932942  PMID: 20830226
Kidney transplantation; Donor
14.  The Bioethics and Utility of Selling Kidneys for Renal Transplantation 
Transplantation proceedings  2008;40(5):1264-1270.
In the fifty years since kidney transplantation was first performed, this procedure has evolved from a highly speculative biomedical endeavor to a medically viable and often standard course of therapy (1). Long-term survival is markedly improved among patients who receive a kidney compared with patients who remain on the waiting list for such an organ (2). As outcomes have improved and more clinical indications have emerged, the number of people awaiting transplantation has grown significantly.
In stark contrast to the robust expansion of the waiting list, the number of available deceased donors has remained relatively constant over the last several years (1). The current mechanism for procuring kidneys relies on voluntary donations by the general public, with the primary motivation being altruism. However, in light of the ever-increasing waiting list, it is the authors’ belief that the current system needs to be revised if supply is ever going to meet demand. In response to this critical organ shortage, different programs have been developed in an attempt to increase organ donation. At present, however, no solution to the problem has emerged. This paper begins by outlining the scope of the problem and current legislation governing the procurement of transplantable organs/tissues in the United States. It continues with an overview of different proposals to increase supply. It concludes by exploring some of the controversy surrounding the proposal to increase donation using financial incentives. Though the following discussion certainly has implications for other transplantable organs, this paper will focus on kidney transplantation because the waiting list for kidneys is by far the longest of all the solid organs; and, as it carries the smallest risk to living donors, is the least ethically problematic.
doi:10.1016/j.transproceed.2008.03.095
PMCID: PMC2504358  PMID: 18589084
Bioethics; Transplantation; End Stage Renal Disease
15.  Ethical issues relating to renal transplantation from prediabetic living donor 
BMC Medical Ethics  2014;15:45.
Background
In Mexico, diabetes mellitus is the main cause of end − stage kidney disease, and some patients may be transplant candidates. Organ supply is limited because of cultural issues. And, there is a lack of standardized clinical guidelines regarding organ donation. These issues highlight the tension surrounding the fact that living donors are being selected despite being prediabetic. This article presents, examines and discusses using the principles of non-maleficience, autonomy, justice and the constitutionally guaranteed right to health, the ethical considerations that arise from considering a prediabetic person as a potential kidney donor.
Discussion
Diabetes is an absolute contraindication for donating a kidney. However, the transplant protocols most frequently used in Mexico do not consider prediabetes as exclusion criteria. In prediabetic persons there are well known metabolic alterations that may compromise the long − term outcomes of the transplant if such donors are accepted. Even so, many of them are finally included because there are not enough donor candidates. Both, families and hospitals face the need to rapidly accept prediabetic donors before the clinical conditions of the recipient and the evolution of the disease exclude him/her as a transplant candidate; however, when using a kidney potentially damaged by prediabetes, neither the donor’s nor the recipient’s long term health is usually considered.
Considering the ethical implication as well as the clinical and epidemiological evidence, we conclude that prediabetic persons are not suitable candidates for kidney donation. This recommendation should be taken into consideration by Mexican health institutions who should rewrite their transplant protocols.
Summary
We argue that the decision to use a kidney from a living donor known to be pre-diabetic or from those persons with family history of T2DM, obesity, hypertension, or renal failure, should be considered unethical in Mexico if the donor bases the decision to donate on socially acceptable norms rather than informed consent as understood in modern medicine.
doi:10.1186/1472-6939-15-45
PMCID: PMC4065609  PMID: 24935278
Renal transplantation; Living donors; Organ donor; Prediabetes; Diabetes mellitus; Clinical ethic; Mexico
16.  Age and the Associations of Living Donor and Expanded Criteria Donor Kidney With Kidney Transplant Outcomes 
Background
Recent studies show a survival advantage with kidney transplant amongst elderly patients compared to those on dialysis.
Study Design
In our present study we examined and compared the association of expanded donor criteria (ECD) kidney and living kidney donation with outcome of kidney transplant across different ages including elderly recipients.
Setting and Participants
Using the Scientific Registry of Transplant Recipients, we identified 145,470 adult kidney transplanted patients. Mortality and death-censored graft failure risks were estimated by Cox proportional regression analyses over a follow-up period with a median of 3.9 years.
Predictors
ECD kidney and living kidney donation and age compared to others.
Outcomes
Mortality and death-censored graft failure risk.
Results
Patients were 45±16 years old and included 40% women and 19% diabetics. Compared to transplanted patients 55-<65 years old, the fully adjusted death-censored graft failure risk was somewhat higher in patients ≥75 years old (HR, 1.30; 95% CI, 1.09–1.56), 35-<55 years (HR, 1.13; 95% CI, 1.08–1.17) and 18-<35 years (HR, 1.64; 95% CI, 1.57–1.71). Compared to non-ECD kidneys, ECD kidneys were significant predictors of mortality in non-elderly patients (18–<35 years: HR, 1.46 [95% CI, 1.19–1.77]; 35-<55 years: HR, 1.23 [95% CI, 1.14–1.32]; and 55-<65 years: HR, 1.26 [95% CI, 1.15–1.38]) and patients aged 65-<70 years (HR, 1.20; 9% CI, 1.05–1.36); but not in other groups of elderly patients (HRs of 1.12 [95% CI, 0.93–1.36] 70-<75 years and 1.04 [95% CI, 0.74–1.47] for ≥75 years). Similar results were found in risk of graft loss. Compared to deceased donor, living kidney was associated with better survival in all age groups and lower graft loss risk in patients aged <70 years.
Limitations
Unmeasured confounders cannot be adjusted for.
Conclusions
Among deceased donors, the ECD kidneys are not associated with either increased mortality or graft failure in recipients over 70 years. Among all types of donors, the persistent association between living donor kidneys and lower all-cause mortality across all ages suggests that, if possible, elderly patients gain longevity from living donor kidney transplant.
doi:10.1053/j.ajkd.2011.12.014
PMCID: PMC3532934  PMID: 22305759
elderly; kidney transplantation; mortality; graft failure; living donor
17.  Prediction of Graft-Versus-Host Disease in Humans by Donor Gene-Expression Profiling 
PLoS Medicine  2007;4(1):e23.
Background
Graft-versus-host disease (GVHD) results from recognition of host antigens by donor T cells following allogeneic hematopoietic cell transplantation (AHCT). Notably, histoincompatibility between donor and recipient is necessary but not sufficient to elicit GVHD. Therefore, we tested the hypothesis that some donors may be “stronger alloresponders” than others, and consequently more likely to elicit GVHD.
Methods and Findings
To this end, we measured the gene-expression profiles of CD4+ and CD8+ T cells from 50 AHCT donors with microarrays. We report that pre-AHCT gene-expression profiling segregates donors whose recipient suffered from GVHD or not. Using quantitative PCR, established statistical tests, and analysis of multiple independent training-test datasets, we found that for chronic GVHD the “dangerous donor” trait (occurrence of GVHD in the recipient) is under polygenic control and is shaped by the activity of genes that regulate transforming growth factor-β signaling and cell proliferation.
Conclusions
These findings strongly suggest that the donor gene-expression profile has a dominant influence on the occurrence of GVHD in the recipient. The ability to discriminate strong and weak alloresponders using gene-expression profiling could pave the way to personalized transplantation medicine.
The donor gene expression profile appears to have a dominant influence on the occurrence of graft-versus-host disease in the recipient.
Editors' Summary
Background.
Human blood contains red blood cells, white blood cells, and platelets, which carry oxygen throughout the body, fight infections, and help blood clot, respectively. Normally, blood-forming (hematopoietic) stem cells in the bone marrow (and their offspring, peripheral blood stem cells) continually provide new blood cells. Tumors that arise from the bone marrow (such as leukemia and lymphoma, two types of hematopoietic tumor) are often treated by a bone marrow or peripheral blood stem cell transplant from a healthy donor to provide new blood-forming stem cells, as a follow-up to chemotherapy or radiotherapy designed to eradicate as much of the tumor as possible. This procedure is called allogeneic hematopoietic cell transplantation (AHCT)—the word allogeneic indicates that the donor and recipient are not genetically identical. When solid organs (for example, kidneys) are transplanted, the recipient's immune system can recognize alloantigens (proteins that vary between individuals) on the donor organ as foreign and reject it. To reduce the risk of rejection, the donor and recipient must have identical major histocompatibility complex (MHC) proteins. MHC matching is also important in AHCT but for further reasons. Here, donor T lymphocytes (a type of white blood cell) can attack the skin and other tissues of the host. This graft versus host disease (GVHD) affects many people undergoing AHCT despite MHC matching either soon after transplantation (acute GVHD) or months later (chronic GVHD). As an aside, the transplant may also act against the tumor itself—this is known as a graft versus leukemia effect.
Why Was This Study Done?
GVHD can usually be treated with drugs that damp down the immune system (immunosuppressive drugs), but it would be preferable to avoid GVHD altogether. Indeed, GVHD continues to be the leading cause of nonrelapse mortality following AHCT. Unfortunately, what determines who will develop GVHD after MHC-matched AHCT is unclear. Although GVHD only develops if there are some mismatches in histocompatibility antigens between the donor and host, it does not inevitably develop. Until now, scientists have mainly investigated whether differences between ACHT recipients might explain this observation. But, in this study, the researchers have examined the donors instead to see whether differences in their immune responses might make some donors stronger “alloresponders” than others and consequently more likely to cause GVHD.
What Did the Researchers Do and Find?
The researchers used a molecular biology technique called microarray expression profiling to examine gene expression patterns in the T lymphocytes of peripheral blood stem cell donors. From these patterns, they identified numerous genes whose expression levels discriminated between donors whose MHC-identical transplant recipient developed GVHD after AHCT (GVHD+ donors) and those whose recipient did not develop GVHD (GVHD− donors). The researchers confirmed that the expression levels of 17 of these genes discriminated between GVHD+ and GVHD− donors using a second technique called quantitative reverse transcriptase polymerase chain reaction. Many of these genes are involved in TGF-β signaling (TGF-β is a protein that helps to control the immune system), cell growth, or proliferation. The researchers also identified four gene pairs that interacted with each other to determine the likelihood that a given donor would induce GVHD. Finally, the researchers computationally retested their data and showed that the measurement of expression levels of each of these genes and of the four interacting gene pairs could correctly identify a donor sample likely to cause GVHD in up to 80% of samples.
What Do These Findings Mean?
These findings provide the first evidence that the donor's gene expression profile influences the development of GVHD in the recipient after AHCT. The researchers suggest that a “dangerous donor” (strong alloresponder) is a key factor in determining whether GVHD occurs after AHCT and propose that gene expression profiling of donor T lymphocytes might identify those donors likely to cause GVHD. Before this approach can be used to reduce the incidence of GVHD after AHCT, these findings need to be confirmed in many more donors. Also, the development of a test that is accurate enough for clinical use—one that does not miss dangerous donors but does not discard too many safe donors—may require the identification of larger groups of interacting genes. But, if it survives further investigation, the concept of a dangerous donor could represent an important advance in transplantation medicine, one that could help clinicians select low-risk donors for AHCT and tailor patients' immunosuppressive drug regimens according to their donor-determined risk of GVHD.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/doi:10.1371/journal.pmed.0040023.
• The National Marrow Donor Program provides information for patients and physicians on all aspects of hematopoietic stem cell transplantation, including GVHD
• The MedlinePlus encyclopedia has pages on bone marrow transplants, GVHD and transplant rejection
• The US National Cancer Institute has a factsheet on bone marrow and peripheral blood stem cell transplantation
doi:10.1371/journal.pmed.0040023
PMCID: PMC1796639  PMID: 17378698
18.  Short-term outcomes for obese live kidney donors and their recipients1,2,3,4,5,6 
Transplantation  2009;88(5):662-671.
Background
Given the association between obesity and kidney disease, transplant professionals have debated the appropriateness of accepting obese live kidney donors. We hypothesized that compared to normal weight donors, donors with elevated body mass index (BMI) would have 1) more peri-operative re-admissions and re-operations, and 2) a greater rise in blood pressure, greater percent rise in serum creatinine, and a greater loss of estimated glomerular filtration rate (eGFR) following nephrectomy.
Methods
Retrospective cohort study using Organ Procurement and Transplantation Network data on live donors who donated kidneys from 7/1/2004 –12/31/2005.
Results
9319 live donor kidney transplants were performed. After eliminating donors with missing BMI data, 5304 donors were analyzed, among whom 2108 (40.0%) were overweight (25 ≤ BMI < 30), 944 (17.8%) were obese (30 ≤ BMI < 35), and 250 (4.7%) were very obese (BMI>=35). Re-admission and re-operation rates did not differ across donor BMI categories. At baseline and at 6 months after nephrectomy, higher BMI was associated with higher blood pressure (p<0.01), but changes in systolic blood pressure from baseline were similar across BMI categories (p=0.40). At six months, decline in eGFR from baseline (p=0.63) and percent change in creatinine (p=0.11) did not differ significantly across groups. Delayed graft function was more common among recipients of kidneys from very obese donors (OR 2.16, CI 1.20 – 3.89, p=0.01), but the rates of recipient allograft failure and mortality across donor BMI groups were similar.
Conclusion
Short-term follow-up data show good outcomes for donors with elevated BMI and their recipients.
doi:10.1097/TP.0b013e3181b27a17
PMCID: PMC2812564  PMID: 19741463
live donor; obesity; kidney transplantation
19.  Kidney paired donation in the presence of donor-specific antibodies 
Kidney international  2013;84(5):1009-1016.
Incompatible donor/recipient pairs with broadly sensitized recipients have difficulty finding a crossmatch-compatible match, despite a large kidney paired donation pool. One approach to this problem is to combine kidney paired donation with lower-risk crossmatch-incompatible transplantation with intravenous immunoglobulin. Whether this strategy is non-inferior compared with transplantation of sensitized patients without donor-specific antibody (DSA) is unknown. Here we used a protocol including a virtual crossmatch to identify acceptable crossmatch-incompatible donors and the administration of intravenous immunoglobulin to transplant 12 HLA-sensitized patients (median calculated panel reactive antibody 98%) with allografts from our kidney paired donation program. This group constituted the DSA(+) kidney paired donation group. We compared rates of rejection and survival between the DSA(+) kidney paired donation group with a similar group of 10 highly sensitized patients (median calculated panel reactive antibody 85%) that underwent DSA(−) kidney paired donation transplantation without intravenous immunoglobulin. At median follow-up of 22 months, the DSA(+) kidney paired donation group had patient and graft survival of 100%. Three patients in the DSA(+) kidney paired donation group experienced antibody-mediated rejection. Patient and graft survival in the DSA(−) kidney paired donation recipients was 100% at median follow-up of 18 months. No rejection occurred in the DSA(−) kidney paired donation group. Thus, our study provides a clinical framework through which kidney paired donation can be performed with acceptable outcomes across a crossmatch-incompatible transplant.
doi:10.1038/ki.2013.206
PMCID: PMC3913053  PMID: 23715120
desensitization; donor-specific HLA antibodies; kidney paired donation; living-donor kidney transplantation
20.  Histocompatibility Testing for Organ Transplantation Purposes in Albania: A Single Center Experience 
Balkan medical journal  2014;31(2):121-125.
Background:
Histocompatibility testing (HT) which includes donor-recipient human leukocyte antigen (HLA) matching, cross-match testing (XMT) and anti-HLA antibody searching are crucial examinations in solid organ transplantation aiming to avoid the hyperacute graft rejection and also to predict the immunological outcome of the graft.
Aims:
The aim of this study was to analyse the tissue typing data collected at the Laboratory of Immunology and Histocompatibility of the University Hospital Center of Tirana, Albania, in order to define those actions that should be taken for improvements in the situation of kidney transplantation in Albania.
Study Design:
Descriptive study.
Methods:
The donor/recipient cross-match testing was performed through a standard complement-dependent cytotoxicity (CDC) assay using separated donor T and B cells that were tested in parallel with the recipient serum sample. All recipient sera were screened for anti-Class I and anti-Class II HLA antibodies using a bead based Luminex anti-HLA antibody screening test. In the case of detected positivity, an allele-specific anti-HLA antibody determination was conducted with the respective Luminex anti-Class I and Class II HLA antibody determination kits.
Results:
A total of 174 recipients and 202 donors were typed for the purpose of living donor kidney transplantation at our laboratory between January 2006 and December 2012. The mean age and female gender proportion of patients were 34.9 years and 34.5%, respectively, and 48.0 years and 65.3% for the donors, respectively. Here, 25.9% of the patients reported a positive complement-dependent cytotoxicity cross-match test and/or a positive anti-HLA antibody testing result. Eighteen patients that were negative for the complement-dependent cytotoxicity cross-match test were positive for anti-HLA antibodies.
Conclusion:
The predominant causes of end-stage renal disease (ESRD) in our patient population are chronic pyelonephritis and glomerulonephritis. The female gender is significantly more frequent among donors, which emphasises the need for more gender equity as far as the altruistic willingness for organ donation is concerned. The significant number of patients with Luminex anti-HLA antibody positivity combined with complement-dependent cytotoxicity cross-match negative results underlines the necessity of using additional methods like cell-based flow cytometry or bead-based Luminex anti-HLA antibody assays for the detection of anti-donor-specific antibodies. We also suggest that the number of kidney transplantations in Albania needs to be increased significantly by expanding it with paired exchange living donation and also by implementing an efficient deceased donor kidney transplantation program.
doi:10.5152/balkanmedj.2014.13045
PMCID: PMC4115930  PMID: 25207182
Albanian population; end-stage renal disease; histocompatibility testing; human leukocyte antigens; kidney transplantation
21.  Substantial variation in the acceptance of medically complex live kidney donors across US renal transplant centers 
Concern exists about accepting live kidney donation from “medically complex donors” -those with risk factors for future kidney disease. This study’s aim was to examine variation in complex kidney donor use across United States (US) transplant centers. We conducted a retrospective cohort study of live kidney donors using Organ Procurement and Transplantation Network data. Donors with hypertension, obesity, or estimated glomerular filtration rate (eGFR) <60 ml/minute/1.73m2 were considered medically complex. Among 9319 donors, 2254 (24.2%) were complex: 1194 (12.8%) were obese, 956 (10.3%) hypertensive, and 392 (4.2%) had low eGFR. The mean proportion of medically complex donors at a center was 24% (range 0 – 65%.) In multivariate analysis, donor characteristics associated with medical complexity included spousal relationship to the recipient (OR 1.29, CI 1.06-1.56, p<0.01), low education (OR 1.19, CI 1.04-1.37, p=0.01), older age (OR 1.01 per year, CI 1.01-1.02, p<0.01), and non-US citizenship (OR 0.70, CI 0.51-0.97, p=0.01). Renal transplant centers with the highest transplant volume (OR 1.26, CI 1.02-1.57, p=0.03), and with a higher proportion of (living donation)/(all kidney transplants) (OR 1.97, CI 1.23-3.16, p<0.01) were more likely to use medically complex donors. Though controversial, the use of medically complex donors is widespread and varies widely across centers.
doi:10.1111/j.1600-6143.2008.02361.x
PMCID: PMC2590588  PMID: 18727695
22.  Willingness to donate: an interview study before liver transplantation 
Journal of Medical Ethics  2004;30(6):544-550.
Objectives: The introduction of the living donation in organ transplantation introduces important new psychological conflicts and ethical questions in the transplantation process. Operation related risks, as well as dependencies in the family structure, generate considerable pressure on potential donors. The aim of the study was to reconstruct the determinants of willingness to donate before transplantation.
Methods: Evaluation of 20 taped and transcribed interviews oriented to current approaches in qualitative interview research. The approach used is based on grounded theory, qualitative content analysis, and the concept of the ideal type.
Results: Before surgery, "openly motivated" donors push for an operation, leaving no room for ambivalence in the evaluation process. They idealise the relationship with the recipient, and link their donation with the individual—partly in subconscious expectations and wishes. In contrast, "openly ambivalent" donors formulate their anxieties and express arguments against donation.
Conclusions: Statements that claim ambivalence towards donation or utterance of arguments against donation indicate earlier coercion. Before transplantation, potential donors should have the opportunity to discuss their emotional situation to help their decision making process.
doi:10.1136/jme.2003.004879
PMCID: PMC1733970  PMID: 15574441
23.  International survey of nephrologists' perceptions and attitudes about rewards and compensations for kidney donation 
Nephrology Dialysis Transplantation  2013;28(6):1610-1621.
…The gap between supply and demand for organs persists worldwide and consequently the quest to narrow this gap continues to explore issues that court controversy, rewards and compensation. Ghahramani et al.'s article provides an interesting additional medical professional's perspective dimension to the knowledge-base concerning rewards and compensation for kidney donation…
Background
Payment for organ donation, whether in the form of incentives, rewards or compensation is highly debated and has been denounced by many professional and legislative bodies. Despite the passionate discussion in the literature, there is very limited data on attitudes and perceptions of physicians about providing rewards or compensation to organ donors. We investigated the relationship between demographic and practice characteristics of nephrologists and their perceptions and attitudes about rewards and compensations for organ donation.
Methods
Using a web-based survey, we explored the views of nephrologists around the world about rewards and compensations for kidney donation. The relationship between attitudes and demographic characteristics of 1280 nephrologists from 74 countries was examined by univariate and multivariable analyses.
Results
Seventy-five percent agreed with donor health insurance, 26% favored direct financial compensation and 31% agreed with financial rewards for unrelated donors. Sixty-six percent believed that rewards will lead to increased donation. Seventy-three percent indicated that rewards will lead to exploitation of the poor and 78% agreed with legislation prohibiting organ sales. Thirty-seven percent believed that rewards will negatively impact deceased-donor transplantation. Nephrologists from India/Pakistan and the Middle East had more favorable views about rewards, while respondents from Latin America and Europe, older than 50, female nephrologists and those practicing in rural areas had less favorable views.
Conclusions
We conclude that a minority of nephrologists favor rewards for donation, many agree with some compensation and a considerable majority favor donor health insurance. Perceptions of nephrologists about rewards and compensation are influenced by age, sex, urban versus rural location and geographic region of practice.
doi:10.1093/ndt/gft079
PMCID: PMC3685310  PMID: 23780679
donor; incentive; questionnaire; renal; survey; transplantation
24.  Differences in Medication Adherence between Living and Deceased Donor Kidney Transplant Patients 
Background: Literature review suggests that adherence to immunosuppressive drugs may be lower in recipients of living than of deceased donor kidney grafts, possibly because of profile differences.
Objective: To compare the level of immunosuppressive adherence levels between patients with deceased and living (-related; -unrelated) donor grafts in Switzerland.
Methods: Using data from two similar cross-sectional studies at two transplant centers in Switzerland, the level of adherence between the two groups was compared. Medication adherence was assessed by self-report or electronic monitoring. Possible explanatory factors included age, beliefs regarding immunosuppressive drugs, depressive symptomatology, pre-emptive transplantation, and the number of transplants received, were also considered. Data were analyzed using logistic regression analysis.
Results: Unadjusted non-adherence odds were 2 to 3 times higher in living-related than deceased donor transplantation (ORs: 2.09-3.05; p<0.05). Adjustment for confounders showed that these differences were associated most with the younger age of living-related subjects and the belief that immunosuppressive drugs are less important for living-related donations.
Conclusion: There is a lower immunosuppressive adherence in recipients of living-related donor kidneys, possibly owing to differences in patient profile (ie, health beliefs regarding their immunosuppressive needs), knowledge of which may enhance adherence if addressed.
PMCID: PMC4089329  PMID: 25013673
Living related transplantation; Immunosuppressant adherence; Kidney transplantation; Donor; Graft
25.  Residence location and likelihood of kidney transplantation 
Background
In a universal, public health care system, access to kidney transplantation should not be influenced by residence location. We determined the likelihood of kidney transplantation from deceased donors among Canadian dialysis patients living in 7 geographic regions. Within each region we also determined whether distance from the closest transplant centre was associated with the likelihood of transplantation.
Methods
A random sample of 7034 subjects initiating dialysis in Canada between 1996 and 2000 was studied. We used Cox proportional hazards models to examine the relation between residence location and the likelihood of kidney transplantation from deceased donors over a median period of 2.4 years.
Results
There were significant differences in the likelihood of kidney transplantation from deceased donors and predicted waiting times between the different geographic regions. For example, the adjusted relative likelihood of transplantation in Alberta was 3.74 (95% confidence interval [CI] 2.95–4.76) compared with the likelihood in Ontario (p < 0.001). These differences persisted after further adjustment for differences in the rate of deceased organ donation. Within regions, patients who resided 50.1–150 km, 150.1–300 km and more than 300 km from the closest transplant centre had a similar adjusted likelihood of receiving a kidney transplant as those who lived less than 50 km away.
Interpretation
The adjusted likelihood of undergoing a kidney transplant from a deceased donor varied substantially between geographic regions in Canada. In contrast, the likelihood of transplantation within regions was not affected by distance from the closest transplant centre.
doi:10.1503/cmaj.051356
PMCID: PMC1550764  PMID: 16940265

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