Making a national donor research program a reality: Concepts for operationalizing a system

Deceased donor research remains an elusive goal for improving organ utilization and function. Many working in this field have cited the barriers that impede the conduct of such trials. Recent reports from the Academy of Medicine and individual authors provide a general framework on which a National Donor Research Program could be built. This paper provides one observer's viewpoint on how such a program could be operationalized.     

The “oldest and coldest” shipped living donor kidneys transplanted through kidney paired donation

To date, thousands of living donor kidneys have been shipped through kidney paired donation (KPD). To expand on this growing segment of living donor transplantation, we evaluated the effect of advanced age donation (“oldest kidneys”) and prolonged cold ischemia time (“coldest kidneys”) on graft function and survival using the National Kidney Registry database from February 2008 to May 2018. Donors were stratified by age at time of donation (<65 or ≥65 years) and kidneys were stratified by cold ischemia time (<16 or ≥16 hours). We evaluated delayed graft function and death‐censored graft failure (DCGF) for up to seven posttransplant years. Of the 2363 shipped living donor kidney transplants, 4.1% of donors were ≥65 years and 6.0% of transplanted kidneys had cold ischemia times ≥16 hours. Delayed graft function and DCGF occurred in 5.2% and 4.7% of cases. There were no significant associations between delayed graft function and donor age (P = .947) or cold ischemia (P = .532). Donor age and cold ischemia time were not predictive of delayed graft function (OR = 0.86,1.20; P = .8, .6) or DCGF (HR = 1.38,0.35, P = .5, .1). These findings may alleviate concerns surrounding the utilization of kidneys from older donors or those originating from distant transplant centers.     

External validation of prediction models for time to death in potential donors after circulatory death

Predicting time to death in controlled donation after circulatory death (cDCD) donors following withdrawal of life‐sustaining treatment (WLST) is important but poses a major challenge. The aim of this study is to determine factors predicting time to circulatory death within 60 minutes after WSLT and validate previously developed prediction models. In a single‐center retrospective study, we used the data of 92 potential cDCD donors. Multivariable regression analysis demonstrated that absent cough‐, corneal reflex, lower morphine dosage, and midazolam use were significantly associated with death within 60 minutes (area under the curve [AUC] 0.89; 95% confidenence interval [CI] 0.87‐0.91). External validation of the logistic regression models of de Groot et al (AUC 0.86; 95% CI 0.77‐0.95), Wind et al (AUC 0.62; 95% CI 0.49‐0.76), Davila et al (AUC 0.80; 95% CI 0.708‐0.901) and the Cox regression model by Suntharalingam et al (Harrell's c‐index 0.63), exhibited good discrimination and could fairly identify which patients died within 60 minutes. Previous prediction models did not incorporate the process of WLST. We believe that future studies should also include the process of WLST as an important predictor.     

Uncontrolled donation after circulatory death: A cohort study of data from a long‐standing deceased‐donor kidney transplantation program

Despite good long‐term outcomes of kidney transplants from controlled donation after circulatory death (DCD) donors, there are few uncontrolled DCD (uDCD) programs. This longitudinal study compares outcomes for all uDCD (N = 774) and all donation after brain death (DBD) (N = 613) kidney transplants performed from 1996 to 2015 at our center. DBD transplants were divided into those from standard‐criteria (SCD) (N = 366) and expanded‐criteria (N = 247) brain‐dead donors (ECD). One‐, 5‐, and 10‐year graft survival rates were 91.7%, 85.7%, and 80.6% for SCD; 86.0%, 75.8%, and 61.4% for ECD; and 85.1%, 78.1%, and 72.2% for uDCD, respectively. Graft survival was worse in recipients of uDCD kidneys than of SCD (P = .004) but better than in transplants from ECD (P = .021). The main cause of graft loss in the uDCD transplants was primary nonfunction. Through logistic regression, donor death due to pulmonary embolism (OR 4.31, 95% CI 1.65‐11.23), extrahospital CPR time ≥75 minutes (OR1.94, 95%CI 1.18‐3.22), and in‐hospital CPR time ≥50 minutes (OR 1.79, 95% CI 1.09‐2.93) emerged as predictive factors of primary nonunction. According to the outcomes of our long‐standing kidney transplantation program, uDCD could help expand the kidney donor pool.     

Increasing the Number of Organ Transplants in the United States by Optimizing Donor Authorization Rates

While recent policies have focused on allocating organs to patients most in need and lessening geographic disparities, the only mechanism to increase the actual number of transplants is to maximize the potential organ supply. We conducted a retrospective cohort study using OPTN data on all “eligible deaths” from 1/1/08 to 11/1/13 to evaluate variability in donor service area (DSA)‐level donor authorization rates, and to quantify the potential gains associated with increasing authorization rates. Despite adjustments for donor demographics (age, race/ethnicity, cause of death) and geographic factors (rural/urban status of donor hospital, statewide participation in deceased‐donor registries) among 52 571 eligible deaths, there was significant variability (p < 0.001) in donor authorization rates across the 58 DSAs. Overall DSA‐level adjusted authorization rates ranged from 63.5% to 89.5% (median: 72.7%). An additional 773–1623 eligible deaths could have been authorized, yielding 2679–5710 total organs, if the DSAs with authorization rates below the median and 75th percentile, respectively, implemented interventions to perform at the level of the corresponding reference DSA. Opportunities exist within the current organ acquisition framework to markedly improve DSA‐level donor authorization rates. Such initiatives would mitigate waitlist mortality while increasing the number of transplants.     

Controlled donation after circulatory death up to 80 years for liver transplantation: Pushing the limit again

Our main objective was to compare liver transplant (LT) results between donation after circulatory death (DCD) and donation after brainstem death (DBD) in our hospital and to analyze, within the DCD group, the influence of age on the results obtained with DCD donors aged >70 years and up to 80 years. All DCD‐LTs performed were analyzed prospectively. The results of the DCD group were compared with those of a control group who received a DBD‐LT immediately after each DCD‐LT. Later, the results obtained within the DCD group were analyzed according to the age of the donors, considering 2 subgroups with a cut‐off point at 70 years. Survival results for LT with DCD and super rapid recovery were not inferior to those obtained in a similar group of patients transplanted with DBD livers. However, the cost of DCD was a higher rate of biliary complications, including ischemic cholangiopathy. Donor age was not a negative factor.     

Impact of a National Controlled Donation After Circulatory Death (DCD) Program on Organ Donation in the United Kingdom: A 10‐Year Study

Organ transplantation is the most successful treatment for some forms of organ failure, yet a lack of organs means many die on the waiting list. In the United Kingdom, the Organ Donation Taskforce was set up to identify barriers to organ donation and in 2008 released its first report (Organ Donation Taskforce Report; ODTR). This study assesses the success since the ODTR and examines the impact of the United Kingdom's controlled donation after circulatory death (DCD) program and the controversies surrounding it. There were 12 864 intended donation after brain death (DBD) or DCD donors from April 2004 to March 2014. When the 5 years preceding the ODTR was compared to the 5 years following, intended DCD donors increased 292% (1187 to 4652), and intended DBD donors increased 11% (3327 to 3698). Organs retrieved per intended DBD donor remained static (3.30 to 3.26), whereas there was a decrease in DCD (1.54 to 0.99) due to a large rise in donors who did not proceed to donation (325 to 2464). The majority of DCD donors who proceeded did so within 30 min from time of withdrawal. Our study suggests further work on converting eligible referrals to organ donation and exploring methods of converting DCD to DBD donors.     

Incentivizing Authorization for Deceased Organ Donation With Organ Allocation Priority: The First 5 Years

The allocation system of donor organs for transplantation may affect their scarcity. In 2008, Israel's Parliament passed the Organ Transplantation Law, which grants priority on waiting lists for transplants to candidates who are first‐degree relatives of deceased organ donors or who previously registered as organ donors themselves. Several public campaigns have advertised the existence of the law since November 2010. We evaluated the effect of the law using all deceased donation requests made in Israel during the period 1998–2015. We use logistic regression to compare the authorization rates of the donors’ next of kin in the periods before (1998–2010) and after (2011–2015) the public was made aware of the law. The authorization rate for donation in the period after awareness was substantially higher (55.1% vs. 45.0%, odds ratio [OR] 1.43, p = 0.0003) and reached an all‐time high rate of 60.2% in 2015. This increase was mainly due to an increase in the authorization rate of next of kin of unregistered donors (51.1% vs. 42.2%). We also found that the likelihood of next‐of‐kin authorization for donation was approximately twice as high when the deceased relative was a registered donor rather than unregistered (89.4% vs. 44.6%, OR 14.27, p < 0.0001). We concluded that the priority law is associated with an increased authorization rate for organ donation.     

The unique moral permissibility of uncontrolled lung donation after circulatory death

Implementing uncontrolled donation after circulatory determination of death (uDCDD) in the United States could markedly improve supply of donor lungs for patients in need of transplants. Evidence from US pilot programs suggests families support uDCDD, but only if they are asked permission for using invasive organ preservation procedures prior to initiation. However, non‐invasive strategies that confine oxygenation to lungs may be applicable to the overwhelming majority of potential uDCDD donors that have airway devices in place as part of standard resuscitation. We propose an ethical framework for lung uDCDD by: (a) initiating post mortem preservation without requiring prior permission to protect the opportunity for donation until an authorized party can be found; (b) using non‐invasive strategies that confine oxygenation to lungs; and (c) maintaining strict separation between the healthcare team and the organ preservation team. Attempting uDCDD in this way has great potential to obtain more transplantable lungs while respecting donor autonomy and family wishes, securing public support, and enabling authorized persons to affirm or cease preservation decisions without requiring evidence of prior organ donation intent. It ensures prioritization of life‐saving, the opportunity to allow willing donors to donate, and respect for bodily integrity while adhering to current ethical norms.     

Comparable graft survival is achievable with the usage of donation after circulatory death liver grafts from donors at or above 70 years of age: A long-term UK national analysis

The aim of the study was to assess the UK donation after circulatory death (DCD) liver transplant experience from donors ≥70 years. Nationwide UK DCD retrospective analysis was conducted between 2001 and 2015 (n = 1163). Recipients were divided into group 1 vs. group 2 (donors 70≥ vs. <70 years, respectively). group 1 (n = 69, 5.9%) recipients were older (median 59 vs. 55 years, p = .001) and had longer waitlist time (128 vs. 84 days; p = .039). 94.2% of group 1 clustered in London and Birmingham, where the two busiest centers are located. group 1 allografts had higher UKDRI and UK DCD Risk Scores but similar WIT and CIT and were more likely to have been imported. Both groups had similar 1-, 3-, and 5-year graft survival (group 1, 90%, 81.4%, and 74% vs. group 2, 88.6%, 81.4%, and 78.6%, respectively; p = .54). Both groups had similar ICU stay length (p = .22), 3-month hepatic artery thrombosis rates (4.4% vs 4.0%; p = .9), and 12-month readmission rates for all biliary complications (20.3% vs 25.7%; p = .32). This study demonstrates that acceptable outcomes are achievable using older grafts in a highly selected cohort at experienced centers. Advanced age should not be an absolute contraindication to utilizing a DCD graft from donors aged ≥70 years.     

The Living Donor Collective: A Scientific Registry for Living Donors

In the setting of an overall decline in living organ donation and new questions about long‐term safety, a better understanding of outcomes after living donation has become imperative. Adequate information on outcomes important to donors may take many years to ascertain and may be evident only by comparing large numbers of donors with suitable controls. Previous studies have been unable to fully answer critical questions, primarily due to lack of appropriate controls, inadequate sample size, and/or follow‐up duration that is too short to allow detection of important risks attributable to donation. The Organ Procurement and Transplantation Network does not follow donors long term and has no prospective control group with which to compare postdonation outcomes. There is a need to establish a national living donor registry and to prospectively follow donors over their lifetimes. In addition, there is a need to better understand the reasons many potential donors who volunteer to donate do not donate and whether the reasons are justified. Therefore, the US Health Resources and Services Administration asked the Scientific Registry of Transplant Recipients to establish a national registry to address these important questions. Here, we discuss the efforts, challenges, and opportunities inherent in establishing the Living Donor Collective.     

Increasing the Use of Kidneys From Unconventional and High‐Risk Deceased Donors

In this paper, we have reviewed the literature and report on kidney donors that are currently used at relatively low rates. Kidneys from donors with acute kidney injury (AKI) seem to have outcomes equivalent to those from donors without AKI, provided one can rule out significant cortical necrosis. Kidneys from donors with preexisting diabetes or hypertension may have marginally lower aggregate survival but still provide patients with a significant benefit over remaining on the wait list. The Kidney Donor Profile Index derives only an aggregate association with survival with a very modest C statistic; therefore, the data indicated that this index should not be the sole reason to discard a kidney, except perhaps in patients with extremely low estimated posttransplant survival scores. It is important to note that the Scientific Registry of Transplant Recipients models of risk adjustment should allay concerns regarding regulatory issues for observed outcomes falling below expectations. The successful utilization of kidneys from donation after cardiac death over the past decade shows how expanding our thinking can translate into more patients benefiting from transplantation. Given the growing number of patients on the wait list, broadening our approach to kidney acceptance could have an important impact on the population with end‐stage renal disease. Many lives could be prolonged by carefully considering use of kidneys that are often discarded.     

How Spain Reached 40 Deceased Organ Donors per Million Population

With 40 donors and more than 100 transplant procedures per million population in 2015, Spain holds a privileged position worldwide in providing transplant services to its patient population. The Spanish success derives from a specific organizational approach to ensure the systematic identification of opportunities for organ donation and their transition to actual donation and to promote public support for the donation of organs after death. The Spanish results are to be highlighted in the context of the dramatic decline in the incidence of brain death and the changes in end‐of‐life care practices in the country since the beginning of the century. This prompted the system to conceive the 40 donors per million population plan, with three specific objectives: (i) promoting the identification and early referral of possible organ donors from outside of the intensive care unit to consider elective non‐therapeutic intensive care and incorporate the option of organ donation into end‐of‐life care; (ii) facilitating the use of organs from expanded criteria and non–standard risk donors; and (iii) developing the framework for the practice of donation after circulatory death. This article describes the actions undertaken and their impact on donation and transplantation activities.     

The Impact of Hydroxyethyl Starch Use in Deceased Organ Donors on the Development of Delayed Graft Function in Kidney Transplant Recipients: A Propensity‐Adjusted Analysis

Our objective was to evaluate the impact of hydroxyethyl starch (HES) use in organ donors after neurologic determination of death (DNDD) on recipient renal graft outcomes. The following data elements were prospectively collected for every DNDD managed by a single organ procurement organization from June 2011 to July 2013: demographics; critical care endpoints; treatments, including the use of HES; graft cold ischemia time (CIT); and the occurrence of recipient delayed graft function (DGF, dialysis in the first week after transplantation). Logistic regression was performed to identify independent predictors of DGF with a p‐value <0.05. The results were then adjusted for each donor's calculated propensity to receive HES. Nine hundred eighty‐six kidneys were transplanted from 529 donors. Forty‐two percent received HES (1217 ± 528 mL) and 35% developed DGF. Kidneys from DNDDs who received HES had a higher crude rate of DGF (41% vs. 31%, p < 0.001). After accounting for the propensity to receive HES, independent predictors of DGF were age (OR 1.02 [1.01–1.04] per year), CIT (OR 1.04[1.02–1.06] per hour), creatinine (OR 1.5 [1.32–1.72] per mg/dL) and HES use (OR 1.41 [1.02–1.95]). HES use during donor management was independently associated with a 41% increase in the risk of DGF in kidney transplant recipients.