Kidney donor outcomes ≥ 50 years after donation

Many living kidney donors (LDs) are young at donation; yet there are little data on long‐term LD follow‐up. We report on 66 LDs who donated ≥50 years ago: 22 (33.3%) are still alive (current age, 78.5 ± 7.25 years); 39 (59%) died (mean age at death, 74.2 ± 12.3 years); and 5 are lost to follow‐up (mean age at last contact, 68.7 ± 4.6 years). Those who died were older at donation (P < .001). Causes of death included 12 (30.8% of deaths) cardiovascular diseases, 9 (23.0%) respiratory failures, 5 (12.8%) malignancies and 4 (10.3%) infections, and 9 (23%) were unknown or miscellaneous. Forty‐nine living donors (74%) developed hypertension at a mean age of 59.9 ± 14.0 years; 12 (18%) developed diabetes at a mean age of 62 ± 19.4 years; and 11 (16.7%) developed proteinuria at a mean age of 60.6 ± 18.2 years—each at a similar incidence as seen in the age‐matched general population. At last follow‐up, the eGFR by CKD‐EPI (mean ± SD) for donors currently alive was 60.2 ± 13.4 mL/min/1.73 m²; for those that died, 54.0 ± 21.5 mL/min/1.73 m²; for those lost to follow‐up, 55.6 ± 7.5 mL/min/1.73 m². ESRD developed in 2 (3.3%). SF‐36 quality of life health survey scores (n = 21) were similar to the age‐matched general population.     

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.     

Psychological Outcomes of Living Liver Donors From a Multicenter Prospective Study: Results From the Adult‐to‐Adult Living Donor Liver Transplantation Cohort Study2 (A2ALL‐2)

Although single‐center and cross‐sectional studies have suggested a modest impact of liver donation on donor psychological well‐being, few studies have assessed these outcomes prospectively among a large cohort. We conducted one of the largest, prospective, multicenter studies of psychological outcomes in living liver donors within the Adult‐to‐Adult Living Donor Liver Transplantation Cohort Study2 (A2ALL‐2) consortium. In total, 271 (91%) of 297 eligible donors were interviewed at least once before donation and at 3, 6, 12, and 24 mo after donation using validated measures. We found that living liver donors reported low rates of major depressive (0–3%), alcohol abuse (2–5%), and anxiety syndromes (2–3%) at any given assessment in their first 2 years after donation. Between 4.7% and 9.6% of donors reported impaired mental well‐being at various time points. We identified significant predictors for donors’ perceptions of being better people and experiencing psychological growth following donation, including age, sex, relationship to recipient, ambivalence and motivation regarding donation, and feeling that donation would make life more worthwhile. Our results highlight the need for close psychosocial monitoring for those donors whose recipients died (n=27); some of those donors experienced guilt and concerns about responsibility. Careful screening and targeted, data‐driven follow‐up hold promise for optimizing psychological outcomes following this procedure for potentially vulnerable donors.     

Report From the American Society of Transplantation Conference on Donor Heart Selection in Adult Cardiac Transplantation in the United States

Cardiac transplantation remains the only definitive treatment for end‐stage heart failure. Transplantation rates are limited by a shortage of donor hearts. This shortage is magnified because many hearts are discarded because of strict selection criteria and concern for regulatory reprimand for less‐than‐optimal posttransplant outcomes. There is no standardized approach to donor selection despite proposals to liberalize acceptance criteria. A donor heart selection conference was organized to facilitate discussion and generate ideas for future research. The event was attended by 66 participants from 41 centers with considerable experience in cardiac donor selection. There were state‐of‐the‐art presentations on donor selection, with subsequent breakout sessions on standardizing the process and increasing utilization of donor hearts. Participants debated misconceptions and established agreement on donor and recipient risk factors for donor selection and identified the components necessary for a future donor risk score. Ideas for future initiatives include modification of regulatory practices to consider extended criteria donors when evaluating outcomes and prospective studies aimed at identifying the factors leading to nonacceptance of available donor hearts. With agreement on the most important donor and recipient risk factors, it is anticipated that a consistent approach to donor selection will improve rates of heart transplantation.     

Long‐Term Outcomes in Belatacept‐ Versus Cyclosporine‐Treated Recipients of Extended Criteria Donor Kidneys: Final Results From BENEFIT‐EXT,a Phase III Randomized Study

In the Belatacept Evaluation of Nephroprotection and Efficacy as First‐Line Immunosuppression Trial–Extended Criteria Donors (BENEFIT‐EXT), extended criteria donor kidney recipients were randomized to receive belatacept‐based (more intense [MI] or less intense [LI]) or cyclosporine‐based immunosuppression. In prior analyses, belatacept was associated with significantly better renal function compared with cyclosporine. In this prospective analysis of the intent‐to‐treat population, efficacy and safety were compared across regimens at 7 years after transplant. Overall, 128 of 184 belatacept MI–treated, 138 of 175 belatacept LI–treated and 108 of 184 cyclosporine‐treated patients contributed data to these analyses. Hazard ratios (HRs) comparing time to death or graft loss were 0.915 (95% confidence interval [CI] 0.625–1.339; p = 0.65) for belatacept MI versus cyclosporine and 0.927 (95% CI 0.634–1.356; p = 0.70) for belatacept LI versus cyclosporine. Mean estimated GFR (eGFR) plus or minus standard error at 7 years was 53.9 ± 1.9, 54.2 ± 1.9, and 35.3 ± 2.0 mL/min per 1.73 m² for belatacept MI, belatacept LI and cyclosporine, respectively (p < 0.001 for overall treatment effect). HRs comparing freedom from death, graft loss or eGFR <20 mL/min per 1.73 m² were 0.754 (95% CI 0.536–1.061; p = 0.10) for belatacept MI versus cyclosporine and 0.706 (95% CI 0.499–0.998; p = 0.05) for belatacept LI versus cyclosporine. Acute rejection rates and safety profiles of belatacept‐ and cyclosporine‐based treatment were similar. De novo donor‐specific antibody incidence was lower for belatacept (p ≤ 0.0001). Relative to cyclosporine, belatacept was associated with similar death and graft loss and improved renal function at 7 years after transplant and had a safety profile consistent with previous reports.     

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.     

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.     

Long‐Term Non–End‐Stage Renal Disease Risks After Living Kidney Donation

Despite generally positive outcomes and high rates of satisfaction, living kidney donors are at risk for both medical and psychosocial problems. In this review, the authors summarize non–end‐stage renal disease (ESRD) risks for donors and describe limitations to the data. We review the evidence of medical risks (e.g. increased cardiovascular disease and mortality, preeclampsia) and psychosocial risks (e.g. mood disturbance, financial burden). We then discuss the evidence of differential risks among subsets and the impact of postdonation events (e.g. development of diabetes). Collectively, available evidence indicates the following. (1) Recognizing the importance of non‐ESRD risks has been overshadowed by analyses of the reported risk of ESRD. This imbalance should be remedied. (2) There is little quantification of the true contribution of donation to medical and psychosocial outcomes. (3) Most studies, to date, have been retrospective, with limited sample sizes and diversity and with less‐than‐ideal controls for comparison of outcomes. (4) Many postdonation events (diabetes and hypertension) can now be reasonably predicted, and their association with adverse outcomes can be quantified. (5) Mechanisms and systems need to be implemented to evaluate and care for donors who develop medical and/or psychosocial problems. (6) Costs to donors are a significant burden, and making donation financially neutral should be a priority.     

Use of expanded-criteria donors and > 85 KDPI kidneys for pediatric kidney transplantation in the United States

Pediatric kidney transplant outcomes associated with expanded-criteria donors (ECD) and high Kidney Donor Profile Index (KDPI) kidneys are unknown. We reviewed the Scientific Registry of Transplant Recipients data from 1987-2017 to identify 96 ECD and 92 > 85 KDPI kidney recipients (<18 years). Using propensity scores, we created comparison groups of 375 non-ECD and 357 ≤ 85 KDPI recipients for comparisons with ECD and > 85 KDPI transplants, respectively. We used Cox regression for patient/graft survival and sequential Cox approach for survival benefit of ECD and > 85 KDPI transplantationvs remaining on the waitlist. After adjustment, ECD recipients were at significantly increased risk of graft failure (adjusted hazard ratio [aHR] = 1.6; P = .001) but not of mortality (aHR = 1.33; P = .15) compared with non-ECD recipients. We observed no survival benefit of ECD transplants vs remaining on the waitlist (aHR = 1.05; P = .83). We found no significant difference in graft failure (aHR = 1.27; P = .12) and mortality (aHR = 1.41; P = .13) risks between > 85 KDPI and ≤ 85 KDPI recipients. However, > 85 KDPI transplants were associated with a survival benefit vs remaining on the waitlist (aHR = 0.41; P = .01). ECD transplantation in children is associated with a high graft loss risk and no survival benefit, whereas > 85 KDPI transplantation is associated with a survival benefit for children vs remaining on the waitlist.     

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.     

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.     

Solid organ donation after death in the United States: Data‐driven messaging to encourage potential donors

US deceased donor solid organ transplantation (dd‐SOT) depends upon an individual's/family's altruistic willingness to donate organs after death; however, there is a shortage of deceased organ donors in the United States. Informing individuals of their own lifetime risk of needing dd‐SOT could reframe the decision‐making around organ donation after death. Using United Network for Organ Sharing (UNOS) data (2007‐2016), this cross‐sectional study identified (1) deceased organ donors, (2) individuals waitlisted for dd‐SOT (liver, kidney, pancreas, heart, lung, intestine), and (3) dd‐SOT recipients. Using US population projections, life tables, and mortality estimates, we quantified probabilities (Pr) of (1) becoming deceased organ donors, (2) needing dd‐SOT, and (3) receiving dd‐SOT. Lifetime Pr (per 100 000 US population) for males and females of becoming deceased organ donors were 212 and 146, respectively, and of needing dd‐SOT were 1323 and 803, respectively. Lifetime Pr of receiving dd‐SOT was 50% for males, 48% for females. Over a lifetime, males were 6.2 and females 5.5 times more likely to need dd‐SOT than to become deceased organ donors. Organ donation is traditionally contextualized in terms of charity toward others. Our analyses yield a new tool, in the form of quantifying an individual's own likelihood of needing dd‐SOT, which may assist with reframing motivations toward deceased donor organ donation.     

An Assessment of HIV‐Infected Patients Dying in Care for Deceased Organ Donation in a United States Urban Center

Organ transplantation is an acceptable option for human immunodeficiency virus (HIV)‐infected patients with end‐stage kidney or liver disease. With worse outcomes on the waitlist, HIV‐infected patients may actually be disproportionately affected by the organ shortage in the United States. One potential solution is the use of HIV‐infected deceased donors (HIVDD), recently legalized by the HIV Organ Policy Equity (HOPE) Act. This is the first analysis of patient‐specific data from potential HIVDD, retrospectively examining charts of HIV‐infected patients dying in care at six HIV clinics in Philadelphia, Pennsylvania from January 1, 2009 to June 30, 2014. Our data suggest that there are four to five potential HIVDD dying in Philadelphia annually who might yield two to three kidneys and three to five livers for transplant. Extrapolated nationally, this would approximate 356 potential HIVDD yielding 192 kidneys and 247 livers annually. However, several donor risk indices raise concerns about the quality of kidneys that could be recovered from HIVDD as a result of older donor age and comorbidities. On the other hand, livers from these potential HIVDD are of similar quality to HIV‐negative donors dying locally, although there is a high prevalence of positive hepatitis C antibody.     

Factors associated with perceived donation‐related financial burden among living kidney donors

The perception of living kidney donation–related financial burden affects willingness to donate and the experience of donation, yet no existing tools identify donors who are at higher risk of perceived financial burden. We sought to identify characteristics that predicted higher risk of perceived financial burden. We surveyed 51 living kidney donors (LKDs) who donated from 01/2015 to 3/2016 about socioeconomic characteristics, predonation cost concerns, and perceived financial burden. We tested associations between both self‐reported and ZIP code–level characteristics and perceived burden using Fisher's exact test and bivariate modified Poisson regression. Donors who perceived donation‐related financial burden were less likely to have an income above their ZIP code median (14% vs. 72%, P = .006); however, they were more likely than donors who did not perceive burden to rent their home (57% vs. 16%, P = .03), have an income <$60 000 (86% vs. 20%, P = .002), or have had predonation cost concerns (43% vs. 7%, P = .03). Perceived financial burden was 3.6‐fold as likely among those with predonation cost concerns and 10.6‐fold as likely for those with incomes <$60 000. Collecting socioeconomic characteristics and asking about donation‐related cost concerns prior to donation might allow transplant centers to target financial support interventions toward potential donors at higher risk of perceiving donation‐related financial burden.     

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.     

UK registry analysis of donor substance misuse and outcomes following pancreas transplantation

Substance abuse is unfortunately common in organ donors. Often, these organs are declined for transplant, not only because of concerns around blood‐borne virus transmission but also because of perceived poor outcomes. In kidney transplantation, previous studies have demonstrated donor smoking status significantly impacts transplant outcome, but intravenous drug use or alcohol dependence does not. This study aims to clarify these issues in pancreas transplantation. Retrospective data on all UK solid organ pancreas transplants from 1994 to 2015 were obtained from the NHSBT UK Transplant Registry. The impact of illicit drug misuse, alcohol abuse, and smoking on graft and patient survival were analyzed using Kaplan‐Meier plots and a Cox regression model. A total of 1175 of the 2317 (49.5%) donors were categorized as substance misusers. Univariate survival analysis revealed no significant impact of substance misuse on 10‐year graft or patient survival. Multivariate analysis confirmed substance misuse was not associated with impaired graft or patient survival. A history of donor substance misuse does not negatively impact 10‐year graft or patient survival following pancreas transplantation. This is a large national registry analysis with long‐term follow‐up data and should therefore provide clinicians with reassurance when considering pancreas grafts from substance misuse donors.