Access to renal transplantation for the elderly in the face of new allocation policy: A review of contemporary perspectives on “older” issues

The benefits of renal transplantation have been demonstrated to extend to the elderly. As a result, more seniors have been placed on the kidney transplant wait list and have received renal allografts in recent years. In June 2013 significant amendments to deceased donor kidney allocation policy were approved to be instituted in 2014 with the goal of increasing overall life years and graft years achieved compared to the current system. Going forward, it is conceivable that transplant centers may perceive a need to adjust practice patterns and modify evaluation and listing criteria for the elderly as the proportion of kidneys distributed to this segment of the wait list would potentially decrease under the new system, further increasing wait times. This review examines contemporary perspectives on access to transplantation for seniors and pertinent issues for this subgroup such as wait time, comorbidity, and evaluation and listing practices. Potential approaches to improve the evaluation of elderly patients being considered for transplant and to increase availability of expanded criteria donor (or higher kidney donor profile index) and living donor organ transplant opportunities while maintaining acceptable outcomes for seniors are explored.     

机械灌注在公民逝世后器官捐献供肾质量维护方面的应用研究进展

公民逝世后器官捐献目前已成为我国器官捐献的主要来源,但是由于供者质量的复杂性,扩大标准供者(ECD)供肾占比增加,从而对供肾的可利用性以及肾移植受者术后的长期预后造成很大的影响.加强供肾质量的维护与评估,对于改善供肾质量、增加供肾获取与利用、改善受者和移植肾长期存活具有重要意义.机械灌注保存作为器官保存的重要方式之一,...     

Renal transplantation in the elderly

Elderly patients are increasingly being considered for kidney transplantation due to a global explosion of the aging population with end-stage renal disease (ESRD). However, mounting scarcity of available organs for transplant has led to a wider disparity between organ supply and demand. Consequently, the criteria for accepting kidneys for transplantation have been extended in an attempt to allow the use of organs from elderly donors or those with significant co-morbidities, so-called “expanded criteria donor” (ECD) kidneys. Excellent outcomes have been achieved from ECD kidneys with appropriate donor and recipient profiling and selection. With increasing recovery efforts directed at older donors, the concept of age-matching is becoming more accepted as a method of optimizing utilization of organs in elderly donors and recipients. Utilization of pulsatile perfusion has further improved ECD outcomes and helped the decision-making process for the UNOS (United Network for Organ Sharing) offer. However, age-related immune dysfunction and associated co-morbidities make the elderly transplant recipients ever more susceptible to complications associated with immunosuppressive agents. Consequently, the elderly population is at a higher risk to develop infections and malignancy in the post-transplant period notwithstanding improved transplant outcomes. Appropriate immunosuppressive agents and dosages should be selected to minimize adverse events while reducing the risk of acute rejections and maximizing patient and renal allograft survival.     

Availability,Utilization and Outcomes of Deceased Diabetic Donor Kidneys; Analysis Based on the UNOS Registry

The number of kidneys obtained from deceased diabetic donors available for transplantation has increased >eightfold increase in the past 15 years. We assessed allograft outcomes associated with deceased diabetic donors and compared them with that of standard and extended criteria donors (ECD) in the UNOS data registry. We identified 1982 recipients of diabetic standard criteria donors over a 10‐year period from 1995 through 2004. Both overall and death‐censored survival of organs from diabetic standard criteria donors was significantly better than that of organs obtained from nondiabetic ECD while inferior to that from nondiabetic standard criteria donors. Compared with ECD donors, diabetic donors had lower serum creatinine, less cold ischemia and these kidneys were less likely to be pump‐perfused. Recipients of diabetic kidneys were younger and less likely to experience delayed graft function compared with recipient of ECD kidneys. More recently, many diabetic donor kidneys have been given to diabetic recipients with early graft survival being similar to that among nondiabetic recipients. These findings demonstrate the potential to expand and to improve utilization of this resource without compromising outcomes for recipients. Improved, evidence‐based evaluation and allocation of deceased diabetic donor kidneys is needed to optimize their use.     

Results of a prospective allocation policy of expanded criteria donors kidneys based on clinical parameters

Re L, Curcio D, Rial M, Goldberg J, Casadei D. Results of a prospective allocation policy of expanded criteria donors kidneys based on clinical parameters. Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01053.x © 2009 John Wiley & Sons A/S. Abstract: The ideal system to allocate expanded criteria donors (ECD) kidneys has not been fully elucidated. In a previous retrospective study, we reported that donor clinical characteristics were more predictive of transplant outcome than biopsy findings. Subsequently, we decided to use ECD kidneys solely based on a clinical scoring system. To elucidate the value of the pre‐transplant biopsy, the patients were divided in two groups according to the suitability of the kidney they received for single or double transplantation as determined by a histological scoring system (HS). All kidneys were transplanted as a single (vs. dual) transplant. We studied whether a HS of the pre‐transplant biopsy was predictive of outcome of single transplant ECD kidneys. Recipients (n = 48) were divided into two groups by whether the histologic system suggested single or double transplants be done. There were no differences between groups in two‐yr outcomes. We conclude that a clinical scoring system can predict which ECD kidney donors can be safely used as single transplants in a cohort of low immunological risk de novo kidney transplant recipients. Use of the clinical scoring system maximizes organ use.     

Inferior long‐term allograft and patient outcomes among recipients of offspring living donor kidneys

While offspring‐to‐parent living donor kidney transplantations may represent an ideal donor–recipient combination to optimize long‐term transplantation outcomes, the sex‐specific long‐term success of these transplantations remains unclear. We hypothesize that allograft and recipient survivals in offspring‐to‐parent living donor kidney transplantation differ between men and women due to donor‐specific alloimmunization during pregnancy. We retrospectively analyzed long‐term allograft and patient survival among men and women who received an offspring living donor kidney compared with those who received other haplotype‐matched living donor kidneys. Based on multivariable Cox proportional hazards modeling of Organ Procurement and Transplantation Network data from 2001 to 2015, we found that both men and women who received offspring living donor kidneys had significantly increased mortality compared with recipients who received nonoffspring living donor kidneys. While male recipients of any living donor kidney had greater risk of mortality and allograft failure than female recipients, there was no significant difference in all‐cause allograft failure or mortality in male versus female recipients of offspring living donor kidney transplantations. Our analysis demonstrated no significant interaction between recipient sex and donor offspring status. We conclude that nonoffspring living donors should be considered whenever feasible for both men and women with multiple donor options.     

Current status of organ transplantation in Japan

To overcome severe donor shortage, Japanese doctors over the years have developed innovative strategies to maximize organs transplanted per brain death donor and expanded the donor pool using living donors. They also used living and marginal organs and drastically improved living donor lung, liver, pancreas and kidney transplantations. Moreover, they initiated ABO blood type incompatible liver transplantation advancements and succeeded in overcoming the blood type barrier in kidney and liver transplantations. Similar efforts are underway for pancreas transplantation. Furthermore, Japanese doctors have developed a nonaggressive step to achieve immunosuppression following organ transplantation by carefully monitoring donor-specific hyporesponsiveness and infectious immunostatus. However, the institution of amendments to allocation systems and the intensification of efforts to decrease living donor morbidity and to increase the number of brain death donors have remained important issues needing attention. Overall, the strategies Japan has adopted to overcome donor shortage can provide useful insights on how to increase organ transplantations.     

Expanded criteria donors for kidney transplantation

The shortage of deceased donor kidneys for transplantation continues to restrict the full application of this lifesaving procedure to all who might benefit. Increasing reliance on donors with characteristics previously thought to be unsuitable for use in transplantation has led to questions about graft outcomes for recipients of such organs. Careful definition of the expanded criteria donor (ECD) for kidney has facilitated modifications of national organ allocation policy that are designed to increase procurement, improve use, decrease cold ischemia time, and lead to improved outcome. The effects of these policy changes in the United States have been studied recently and are reviewed here. In addition, the impact of ECD kidney transplantation on mortality risk among candidates awaiting deceased donor renal transplantation is examined. Further studies of ECD organs and their recipients are needed to optimize the use of these scarce resources.     

Centers for Disease Control ‘High‐Risk’ Donors and Kidney Utilization

The aims of this study were to determine whether Centers for Disease Control high risk (CDCHR) status of organ donors affects kidney utilization and recipient survival. Data from the Scientific Registry of Transplant Recipients were used to examine utilization rates of 45 112 standard criteria donor (SCD) deceased donor kidneys from January 1, 2005, and February 2, 2009. Utilization rates for transplantation were compared between CDCHR and non‐CDCHR kidneys, using logistic regression to control for possible confounders. Cox regression was used to determine whether CDCHR status independently affected posttransplant survival among 25 158 recipients of SCD deceased donor kidneys between January 1, 2005, and February 1, 2008. CDCHR kidneys were 8.2% (95% CI 6.9–9.5) less likely to be used for transplantation than non‐CDCHR kidneys; after adjusting for other factors, CDCHR was associated with an odds ratio of utilization of 0.67 (95% CI 0.61–0.74). After a median 2 years follow‐up, recipients of CDCHR kidneys had similar posttransplant survival compared to recipients of non‐CDCHR kidneys (hazard ratio 1.06, 95% CI 0.89–1.26). These findings suggest that labeling donor organs as ‘high risk’ may result in wastage of approximately 41 otherwise standard kidneys per year.     

10 Jahre „Eurotransplant Senior Program“

On 1 January 1999 Eurotransplant started the “Eurotransplant Senior Program” (ESP), the first program worldwide for age-matched kidney allocation and transplantation of expanded criteria donors (ECD). By now more than 4.300 kidneys from donors aged ≥65 were transplanted into recipients ≥65, with local or regional allocation according only to blood group compatibility and waiting time. Compared to ongoing dialysis, renal transplantation in the ESP offers longer patient survival and improved quality of life. The article evaluates the results of the ESP and of other studies dealing with renal transplantation of old donor kidneys into aged recipients. Specific aspects like the unexpectedly high acute rejection rate and ways to assess the residual renal function of aged donor kidneys are covered as well as the specific post-transplant risks of aged recipients.     

Call to Develop a Standard Acquisition Charge Model for Kidney Paired Donation

We propose a Medicare Demonstration Project to develop a standard acquisition charge for kidney paired donation. A new payment strategy is required because Medicare and commercial insurance companies may not directly pay living donor costs intended to lead to transplantation of a beneficiary of a different insurance provider. Until the 1970s, when organ procurement organizations were empowered to serve as financial intermediaries to pay the upfront recovery expenses for deceased donor kidneys before knowing the identity of the recipient, there existed similar limitations in the recovery and placement of deceased donor organs. Analogous to the recovery of deceased donor kidneys, kidney paired donation requires the evaluation of living donors before identifying their recipient. Tissue typing, crossmatching and transportation of living donors or their kidneys represent additional financial barriers. Finally, the administrative expenses of the organizations that identify and coordinate kidney paired donation transplantation require reimbursement akin to that necessary for organ procurement organizations. To expand access to kidney paired donation for more patients, we propose a model to reimburse paired donation expenses analogous to the proven strategy used for over 30 years to pay for deceased donor solid organ transplantation in America.     

Allocation of deceased donor kidneys: A review of international practices

The demand for kidney transplantation continues to exceed the availability of deceased donor kidneys. Balancing the overarching principles of the optimal use of (utility) and equal access to (equity) this scarce resource requires a sophisticated allocation system. This review will examine how various factors are addressed in allocation systems around the world to strike a balance between utility and equity.     

Standard criteria donor pancreas donation status is associated with improved kidney transplant outcomes

Abstract: Background: Organ donor characteristics can be used to predict outcomes in kidney transplantation. We hypothesized that pancreas donation status could reflect organ quality and be predictive of kidney graft outcomes following Standard Criteria Donor (SCD) kidney transplantation. Methods: We performed a retrospective analysis of deceased donor kidney alone (DD KA) transplants reported to SRTR from 1992 to 2005. Group 1 = kidney alone recipients from pancreas donors (KA, P+) and Group 2 = kidney alone recipients from non‐pancreas donors (KA, P?). We compared patient and graft survival between groups at 10‐yr post‐transplant. Results: Group 1 (KA, P+) comprised 19 633 (20%) recipients and Group 2 (KA, P?) comprised 78 737 (80%) recipients. Ten‐yr graft survival for Group 1 vs. Group 2 was 42.6% and 36.9% (p < 0.0001), respectively. Pancreas donation status (non‐pancreas donor) was associated with a hazard ratio for graft loss of 1.23 on univariate analysis (p < 0.0001), and KA, P‐remained an independent risk factor for graft failure at 10 yr, HR 1.09 (p < 0.0001). Conclusion: Donor pancreas donation status is an independent predictor of improved outcomes of SCD kidney recipients. Further study of the pancreas organ donor pre‐procurement is warranted to optimize not only pancreas utilization but also kidney graft outcomes.     

The Broad Spectrum of Quality in Deceased Donor Kidneys

The quality of the deceased donor organ clearly is one of the most crucial factors in determining graft survival and function in recipients of a kidney transplant. There has been considerable effort made towards evaluating these organs culminating in an amendment to allocation policy with the introduction of the expanded criteria donor (ECD) policy.
Our study, from first solitary adult deceased donor transplant recipients from 1996 to 2002 in the National Scientific Transplant Registry database, presents a donor kidney risk grade based on significant donor characteristics, donor–recipient matches and cold ischemia time, generated directly from their risk for graft loss. We investigated the impact of our donor risk grade in a naïve cohort on short- and long-term graft survival, as well as in subgroups of the population.
The projected half-lives for overall graft survival in recipients by donor risk grade were I (10.7 years), II (10.0 years), III (7.9 years), IV (5.7 years) and V (4.5 years). This study indicates that there is great variability in the quality of deceased donor kidneys and that the assessment of risk might be enhanced by this scoring system as compared to the simple two-tiered system of the current ECD classification.     

Kidneys from Deceased Donors: Maximizing the Value of a Scarce Resource

Donor age is a significant risk factor for graft loss after kidney transplantation. We investigated the question whether significant graft years were being lost through transplantation of younger donor kidneys into older recipients with potentially shorter lifespans than the organs they receive. We examined patient and graft survival for deceased donor kidney transplants performed in the United States between the years 1990 and 2002 by Kaplan-Meier plots. We categorized the distribution of deceased donor kidneys by donor and recipient age. Subsequently, we calculated the actual and projected graft survival of transplanted kidneys from younger donors with the patient survival of transplant recipients of varying ages. Over the study period, 16.4% (9250) transplants from donors aged 15-50 were transplanted to recipients over the age of 60. At the same time, 73.6% of donors above the age of 50 were allocated to recipients under the age of 60. The graft survival of grafts from younger donors significantly exceeded the patient survival of recipients over the age of 60. The overall projected improvement in graft survival, by excluding transplantation of younger kidneys to older recipients, was approximately 3 years per transplant. Avoiding the allocation of young donor kidneys to elderly recipients, could have significantly increased the overall graft life, by a total 27,500 graft years, between 1990 and 2002, with projected cost savings of about 1.5 billion dollars.     

Kidney and pancreas transplantation

Data from the Scientific Registry of Transplant Recipients offer a unique and comprehensive view of US trends in kidney and pancreas waiting list characteristics and outcomes, transplant recipient and donor characteristics, and patient and allograft survival. Important findings from our review of developments during 2002 and the decade's transplantation trends appear below.
The kidney waiting list has continued to grow, increasing from 47 830 in 2001 to 50 855 in 2002. This growth has occurred despite the increasing importance of living donor transplantation, which rose from 28% of total kidney transplants in 1993 to 43% in 2002.
Policies and procedures to expedite the allocation of expanded criteria donor (ECD) kidneys were developed and implemented during 2002, when 15% of deceased donor transplants were performed with ECD kidneys. Unadjusted 1- and 5-year deceased donor kidney allograft survivals were 81% and 51% for ECD kidney recipients, and 90% and 68% for non-ECD kidney recipients, respectively.
Although more patients have been placed on the simultaneous kidney-pancreas waiting list, the number of these transplants dropped from a peak of 970 in 1998 to 905 in 2002. This decline may be due to competition for organs from increasing numbers of isolated pancreas and islet transplants.     

Organ donation and utilization in the USA

The processes leading to donor identification, consent, organ procurement, and allocation continue to dominate debates and efforts in the field of transplantation. A considerable shortage of donors remains while the number of patients needing organ transplantation increases.
This article reviews the main trends in organ donation practices and procurement patterns from both deceased and living sources in the USA. Although there have been increases in living donation in recent years, 2002 witnessed a much more modest growth of 1%. Absolute declines in living liver and lung donation were also noted in 2002.
In 2002, the number of deceased donors increased by only 1.6% (101 donors). Increased donation from deceased donors provides more organs for transplantation than a comparable increase in living donation, because on average 3.6 organs are recovered from each deceased donor. The total number of organs recovered from deceased donors increased by 2.1% (462 organs). Poor organ quality continued to be the major reason given for nonrecovery of consented organs from deceased donors.
The kidney is the organ most likely to be discarded after recovery. Over the past decade the discard rate of recovered kidneys has increased from 6% to 11%. Many of these are expanded criteria donor kidneys.     

Ethical Issues in Dialysis Aaron SpitalSeries Editor: Soliciting Kidneys on Web Sites: Is it Fair?

The Internet serves as a meeting place where people in need of kidney transplants can find strangers willing to donate. While Good Samaritan donors located via the Internet increase the number of kidneys available for transplantation, they also raise ethical issues. This practice alters the pattern for distributing kidneys from unrelated living donors and raises questions of justice in the allocation of organs. It is unclear if commercial forces are at play in the arrangements made between potential donors and recipients via the Internet. While it is unfair that some recipients do not have suitable willing living donors, Web sites help to balance the inequity by increasing the opportunity to find a living donor; they also benefit other potential recipients by reducing the waiting list. However, although these Web sites are probably here to stay, Internet donor-recipient matches can have negative consequences that we need to minimize. Suggested strategies include regulated, monitored Web sites and the development of more anonymous organ donor programs.     

Expanded criteria donors: process and outcomes

Expanded criteria donor (ECD) kidneys are transplantable deceased donor (DD) kidneys for which the average patient, graft survival, and renal function are inferior when compared to standard criteria DD kidneys. Although the term ECD kidneys has been used since the early 1990s to describe kidneys with various characteristics associated with poorer outcomes, the concept has been formally implemented in U.S. organ allocation. A DD kidney is considered to be an ECD organ if the estimated adjusted risk of graft failure is > or = 70% (RR > or = 1.70) compared to DD kidneys with standard characteristics of transplant suitability. The donor characteristics that define an ECD kidney include age > or = 60 years, or age 50-59 years plus two of the following: cerebrovascular accident as the cause of death, preexisting hypertension, or terminal serum creatinine greater than 1.5 mg/dl. In the aggregate, recipients of ECD kidneys have improved survival compared to end-stage renal disease (ESRD) patients on the kidney transplant waiting list. Patient survival is 5% lower at 1 year and 8-12% lower at 3-5 years for ECD kidney recipients. Adjusted graft survival in ECD kidneys is 8% lower at 1 year and 15-20% lower at 3-5 years after transplantation compared to standard criteria donor kidneys. However, patients less than 40 years of age, African Americans, Asians for whom the median waiting time is less than 1350 days receive no survival benefit from ECD kidney transplantation. Informed choice by the potential recipient is a prominent feature of the allocation policy regarding ECD kidneys. Since there are recipient characteristics associated with no survival benefit following ECD transplantation, nephrologists who refer patients for kidney transplantation should be familiar with the combination of donor and recipient factors that are likely to yield detrimental results.     

Clinical issues in renal transplantation in the elderly

Kidney transplantation is the best renal replacement therapy option and is superior to dialysis in elderly end‐stage renal disease (ESRD) patients. Furthermore, the outcome of transplantation in the elderly is comparable to younger patients in terms of allograft survival. The exact nature of this phenomenon is not completely clear. As the elderly population continues to grow, it becomes more important to identify specific issues associated with kidney transplantation. In particular, elderly transplant recipients might have a lower chance of acute rejection as their immune systems seem to be less reactive. This might predispose elderly recipients to greater risk of post‐transplant infectious complications or malignancies. Furthermore, due to differences in pharmacokinetics, elderly recipients might require lower doses of immunosuppressive medication. As the main cause of graft failure in the elderly is death with a functioning graft and also considering the scarcity of donor organs, it might make sense to recommend transplanting elderly recipients with extended criteria donor kidneys. This approach would balance shorter patient survival compared to younger recipients. In conclusion, old age should not preclude ESRD patients from kidney transplantation. However, specific differences that have to do with immunosuppression and other aspects of managing elderly transplant recipients should be considered.