Safety and Outcomes in 100 Consecutive Donation After Circulatory Death Liver Transplants Using a Protocol That Includes Thrombolytic Therapy

Donation after circulatory death (DCD) liver transplantation (LT) reportedly yields inferior survival and increased complication rates compared with donation after brain death (DBD). We compare 100 consecutive DCD LT using a protocol that includes thrombolytic therapy (late DCD group) to an historical DCD group (early DCD group n = 38) and a cohort of DBD LT recipients (DBD group n = 435). Late DCD LT recipients had better 1‐ and 3‐year graft survival rates than early DCD LT recipients (92% vs. 76.3%, p = 0.03 and 91.4% vs. 73.7%, p = 0.01). Late DCD graft survival rates were comparable to those of the DBD group (92% vs. 93.3%, p = 0.24 and 91.4% vs. 88.2%, p = 0.62). Re‐transplantation occurred in 18.4% versus 1% for the early and late DCD groups, respectively (p = 0.001). Patient survival was similar in all three groups. Ischemic‐type biliary lesions (ITBL) occurred in 5%, 3%, and 0.2% for early DCD, late DCD, and DBD groups, respectively, but unlike in the early DCD group, in the late DCD group ITBL was endoscopically managed and resolved in each case. Using a protocol that includes a thrombolytic therapy, DCD LT yielded patient and graft survival rates comparable to DBD LT.     

Local Expansion of Donation After Circulatory Death Kidney Transplant Activity Improves Waitlisted Outcomes and Addresses Inequities of Access to Transplantation

In the United Kingdom, donation after circulatory death (DCD) kidney transplant activity has increased rapidly, but marked regional variation persists. We report how increased DCD kidney transplant activity influenced waitlisted outcomes for a single center. Between 2002–2003 and 2011–2012, 430 (54%) DCD and 361 (46%) donation after brain death (DBD) kidney‐only transplants were performed at the Cambridge Transplant Centre, with a higher proportion of DCD donors fulfilling expanded criteria status (41% DCD vs. 32% DBD; p = 0.01). Compared with U.K. outcomes, for which the proportion of DCD:DBD kidney transplants performed is lower (25%; p < 0.0001), listed patients at our center waited less time for transplantation (645 vs. 1045 days; p < 0.0001), and our center had higher transplantation rates and lower numbers of waiting list deaths. This was most apparent for older patients (aged >65 years; waiting time 730 vs. 1357 days nationally; p < 0.001), who received predominantly DCD kidneys from older donors (mean donor age 64 years), whereas younger recipients received equal proportions of living donor, DBD and DCD kidney transplants. Death‐censored kidney graft survival was nevertheless comparable for younger and older recipients, although transplantation conferred a survival benefit from listing for only younger recipients. Local expansion in DCD kidney transplant activity improves survival outcomes for younger patients and addresses inequity of access to transplantation for older recipients.     

A Multicenter Study on Long‐Term Outcomes After Lung Transplantation Comparing Donation After Circulatory Death and Donation After Brain Death

The implementation of donation after circulatory death category 3 (DCD3) was one of the attempts to reduce the gap between supply and demand of donor lungs. In the Netherlands, the total number of potential lung donors was greatly increased by the availability of DCD3 lungs in addition to the initial standard use of donation after brain death (DBD) lungs. From the three lung transplant centers in the Netherlands, 130 DCD3 recipients were one‐to‐one nearest neighbor propensity score matched with 130 DBD recipients. The primary end points were primary graft dysfunction (PGD), posttransplant lung function, freedom from chronic lung allograft dysfunction (CLAD), and overall survival. PGD did not differ between the groups. Posttransplant lung function was comparable after bilateral lung transplantation, but seemed worse after DCD3 single lung transplantation. The incidence of CLAD (p = 0.17) nor the freedom from CLAD (p = 0.36) nor the overall survival (p = 0.40) were significantly different between both groups. The presented multicenter results are derived from a national context where one third of the lung transplantations are performed with DCD3 lungs. We conclude that the long‐term outcome after lung transplantation with DCD3 donors is similar to that of DBD donors and that DCD3 donation can substantially enlarge the donor pool.     

Donation After Circulatory Determination of Death Lung Transplantation for Pulmonary Arterial Hypertension: Passing the Toughest Test

Lung transplantation (LTx) is a therapeutic option for severe pulmonary arterial hypertension (PAH) patients failing optimal medical therapy. The use of donation after circulatory determination of death (DCDD) donor lungs for PAH LTx has rarely been reported, primarily reflecting concerns that DCDD lungs represent extended criteria donors, at risk of morbidity and mortality. A retrospective study of all Alfred Hospital DCDD and DNDD (donation after neurologic determination of death) PAH LTx was undertaken. Protocolized fluid/inotrope/ventilator and extracorporeal membrane oxygenation (ECMO) strategies were utilized. Since our first DCDD LTx in 2006, 512 LTx have been performed. Of 31 PAH recipients, 11 received DCDD lungs (11% of DCDD LTx) and 20 received DNDD lungs (5% of DNDD LTx) (p = 0.04). Only one PAH patient died on the LTx waiting list. Peri‐LTx ECMO was utilized in 3/11 (27%) DCDD and 6/20 (30%) DNDD PAH LTx (p = 0.68). Primary graft dysfunction, intensive care, and overall stay were the same in both groups. Survival at 1 and 8 years was 100% and 80% for DCDD versus 100% and 70% for DNDD LTx (p = 0.88), respectively. In conclusion, excellent results can be achieved for PAH LTx. DCDD donor lungs are not extended lungs per se having passed the toughest test.     

Sociodemographic Determinants of Waitlist and Posttransplant Survival Among End‐Stage Liver Disease Patients

While regional organ availability dominates discussions of distribution policy, community‐level disparities remain poorly understood. We studied micro‐geographic determinants of survival risk and their distribution across Donor Service Areas (DSAs). Scientific Registry of Transplant Recipients records for all adults waitlisted for liver transplantation 2002–2014 were reviewed. The primary exposure variables were county‐level sociodemographic risk, as measured by the Community Health Score (CHS), a previously‐validated composite index local health conditions, and distance to listing transplant center. Among 114 347 patients, the median CHS was 19.4 (range: 0–40). Compared the lowest risk counties (CHS 1–10), highest‐risk counties (CHS 31–40) had more black (14.6% vs. 5.4%), publicly insured (44.9% vs. 33.0), and remote candidates (34.0% vs. 15.1% living >100 miles away). Higher‐CHS candidates had greater waitlist mortality in Cox multivariable (HR 1.16 for CHS 31–40, 95% CI 1.11–1.21) and competing risks analysis (sHR 1.07, 95% CI 0.99–1.14). Post‐transplant survival was similar across CHS quartiles. Living >25 miles from the transplant center conferred excess mortality risk (sHR 1.08, 95% CI 1.03–1.12). Proposed distribution changes would disproportionately impact DSAs with more high‐CHS or distant candidates. Low‐income, rural and minority patients experience excess mortality while awaiting transplant, and risk disproportionately worse outcomes with reduced organ availability under current proposals.     

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.     

Variation in Biliary Complication Rates Following Liver Transplantation: Implications for Cost and Outcome

Although biliary complications (BCs) have a significant impact on the outcome of liver transplantation (LT), variation in BC rates among transplant centers has not been previously analyzed. BC rate, LT outcome and spending were assessed using linked Scientific Registry of Transplant Recipients and Medicare claims (n = 16 286 LTs). Transplant centers were assigned to BC quartiles based upon risk‐adjusted observed to expected (O:E) ratio of BC separately for donation after brain death (DBD) and donation after cardiac death (DCD) donors. The median incidence of BC was 300% greater in the highest versus lowest DBD quartiles (19.0% vs. 5.9%) and varied 250% between DCD quartiles (20.3%–8.4%). Donor and recipient characteristics suggest that high BC centers actually used lower donor risk index organs, fewer split livers and fewer imports (p < 0.001 for all). Transplant at a center in the highest O:E quartile was associated with increased posttransplant mortality (adjusted hazard ratio [aHR] 2.53, p = 0.007) in DCD transplant and increased graft loss (aHR 1.21, p = 0.02) in DBD transplant. Medicare spending was $22 895 (p < 0.0001) higher at centers in highest versus lowest BC quartile. In summary, BC rates vary widely among transplant centers and higher rates are a marker for an increased risk of death, graft failure and health‐care spending.     

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.     

The Use of Donation After Cardiac Death Allografts Does Not Increase Recurrence of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) recurrence in patients undergoing liver transplantation (LT) with donation after brain death (DBD) and donation after cardiac death (DCD) allografts has not previously been investigated. Rates and patterns of HCC recurrences were investigated in patients undergoing DBD (N = 1633) and DCD (N = 243) LT between 2003 and 2012. LT for HCC was identified in 397 patients (340 DBD and 57 DCD). No difference in tumor number (p = 0.26), tumor volume (p = 0.34) and serum alphafetoprotein (AFP) (p = 0.47) was seen between the groups. HCC recurrence was identified in 41 (12.1%) patients in the DBD group and 7 (12.3%) patients in the DCD group. There was no difference in recurrence‐free survival (p = 0.29) or cumulative incidence of HCC recurrence (p = 0.91) between the groups. Liver allograft was the first site of recurrence in 22 (65%) patients in the DBD group and two (37%) patients in the DCD group (p = 0.39). LT for HCC with DBD and DCD allografts demonstrate no difference in the rate of HCC recurrence. Previously published differences in survival demonstrated between recipients with HCC receiving DBD and DCD allografts despite statistical adjustment can likely be explained by practice patterns not captured by variables contained in the SRTR database.     

Adult Living Donor Liver Transplantation for Acute‐on‐Chronic Liver Failure in High–Model for End‐Stage Liver Disease Score Patients

The large volume of adult living donor liver transplantations (ALDLTs) at our center affords a unique opportunity to examine the impact of acute‐on‐chronic liver failure (ACLF) among high–Model for End‐Stage Liver Disease MELD score patients. From February 1998 to March 2010, 1958 cirrhotic recipients were analyzed to study the relationship between MELD scores and ALDLT outcomes. A total of 327 high‐MELD score recipients were categorized into ACLF and non‐ACLF groups, and their outcomes were compared. The 5‐year graft and patient survival in the high‐MELD group were 75.2% and 76.4%, respectively, which were significantly worse than the low and intermediate MELD groups. The presence of ACLF associated with higher MELD scores appeared to be the dominant factor responsible for the inferior results of patients with MELD score of 30–34 points. The 5‐year graft survivals in the ACLF group was 70.5% and in the non‐ACLF group it was 81.0% (p = 0.035). Therefore, ALDLT should be performed as soon as possible in high‐MELD score patients prior to ACLF development. Moreover, ACLF patients should be separately categorized when analyzing the outcomes of ALDLT. ALDLT for ACLF patients should not be discouraged because favorable outcomes can be expected through timely ALDLT and comprehensive management.     

Improving the Outcomes of Organs Obtained From Controlled Donation After Circulatory Death Donors Using Abdominal Normothermic Regional Perfusion

The use of donation after circulatory death (DCD) has increased significantly during the past decade. However, warm ischemia results in a greater risk for transplantation. Indeed, controlled DCD (cDCD) was associated with inferior outcomes compared with donation after brain death. The use of abdominal normothermic regional perfusion (nRP) to restore blood flow before organ recovery in cDCD has been proposed as better than rapid recovery to reverse the effect of ischemia and improve recipients’ outcome. Here, the first Spanish series using abdominal nRP as an in situ conditioning method is reported. A specific methodology to avoid restoring circulation to the brain after death determination is described. Twenty‐seven cDCD donors underwent abdominal nRP during at least 60 min. Thirty‐seven kidneys, 11 livers, six bilateral lungs, and one pancreas were transplanted. The 1‐year death‐censored kidney survival was 91%, and delayed graft function rate was 27%. The 1‐year liver survival rate was 90.1% with no cases of ischemic cholangiopathy. Transplanted lungs and pancreas exhibited primary function. The use of nRP may represent an advance to increase the number and quality of grafts in cDCD. Poor results in cDCD livers could be reversed with nRP. Concerns about restoring brain circulation after death are easily solved.     

Efficacy and Safety Outcomes of Extended Criteria Donor Kidneys by Subtype: Subgroup Analysis of BENEFIT‐EXT at 7 Years After Transplant

The phase III Belatacept Evaluation of Nephroprotection and Efficacy as First‐Line Immunosuppression Trial–Extended Criteria Donors Trial (BENEFIT‐EXT) study compared more or less intensive belatacept‐based immunosuppression with cyclosporine (CsA)–based immunosuppression in recipients of extended criteria donor kidneys. In this post hoc analysis, patient outcomes were assessed according to donor kidney subtype. In total, 68.9% of patients received an expanded criteria donor kidney (United Network for Organ Sharing definition), 10.1% received a donation after cardiac death kidney, and 21.0% received a kidney with an anticipated cold ischemic time ≥24 h. Over 7 years, time to death or graft loss was similar between belatacept‐ and CsA‐based immunosuppression, regardless of donor kidney subtype. In all three donor kidney cohorts, estimated mean GFR increased over months 1–84 for belatacept‐based treatment but declined for CsA‐based treatment. The estimated differences in GFR significantly favored each belatacept‐based regimen versus the CsA‐based regimen in the three subgroups (p < 0.0001 for overall treatment effect). No differences in the safety profile of belatacept were observed by donor kidney subtype.     

Impact of donation after circulatory death donor allografts on outcomes following liver transplantation for fulminant hepatic failure in the United States

Limited data exist regarding the impact of donation after circulatory death (DCD) allografts on outcomes following liver transplantation in fulminant hepatic failure (FHF). Utilizing the Scientific Registry of Transplant Recipients (SRTR), we compared outcomes after DCD in FHF to donation after brain death (DBD) in FHF and DCD in non-FHF over a 15-year period. Primary outcome measures were graft and patient survival. A total of 117, 3437, and 4379 recipients underwent DCD-FHF, DBD-FHF and DCD-non-FHF, respectively. One-year graft survival in DCD-FHF was inferior to DBD-FHF (72.9% vs. 83.8%, p = .002), but comparable to DCD-non-FHF (72.9% vs. 82.7%, p = .23). However, 3- and 5-year graft survival in DCD-FHF were comparable to DBD-FHF (67.9 vs. 77.6%, p = .63; 57.8% vs. 73.2%, p = .27) and DCD-non-FHF (67.9% vs. 72.9%, p = .44; 57.8% vs. 66.6%, p = .06). One-, 3-, and 5-year patient survival were also comparable among the three groups. Graft and patient survival in DCD-FHF improved over the study period. Multivariable analysis identified recipient age, male gender, African American ethnicity, donor age, and cold ischemia time as predictors of graft and patient survival in FHF, while DCD status was only predictive of graft survival. Long-term graft survival and patient survival in DCD-FHF are comparable to DBD-FHF and DCD-non-FHF. Consideration of DCD in FHF could help expand the donor pool in this subset of critically ill patients.     

A Comparison of Request Process and Outcomes in Donation After Cardiac Death and Donation After Brain Death: Results From a National Study

Available literature points to healthcare providers’ discomfort with donation after cardiac death (DCD) and their perception of public reluctance toward the procedure. Using a national sample, we report on the communication content of actual DCD and donation after brain death (DBD) approaches by organ procurement organization (OPO) requesters and compare family decision makers’ (FDMs’) experiences of both modalities. We recruited 1601 FDMs using a validated protocol; 347 (21.7%) were of potential DCD donors. Semistructured telephone interviews yielded FDMs’ sociodemographic data, donation attitudes, assessment of approach, final outcomes, and substantiating reasons. Initial analysis consisted of bivariate analyses. Multilevel mixture models compared groups representing authorization outcome and DCD/DBD status. No significant differences in family authorization were found between DCD and DBD cases. Statistically significant associations were found between sociodemographic characteristics and authorization, with white FDMs more likely to authorize DCD or DBD than black FDMs. FDMs of both modalities had similar evaluations of requester skills, topics discussed, satisfaction, and refusal reasons. The findings suggest that the DCD/DBD distinction may not be notable to families. We recommend the use of similar approach strategies and communication skills and the development of education campaigns about the public's acceptance of DCD.     

Recipient Outcomes Following Transplantation of Allografts From Live Kidney Donors Who Subsequently Developed End‐Stage Renal Disease

Live kidney donors have an increased risk of end‐stage renal disease (ESRD) compared with nondonors; however, it is unknown whether undetected, subclinical kidney disease exists at donation that subsequently contributes to this risk. To indirectly test this hypothesis, the authors followed the donated kidneys, by comparing the outcomes of 257 recipients whose donors subsequently developed ESRD with a matched cohort whose donors remained ESRD free. The compared recipients were matched on donor (age, sex, race/ethnicity, donor–recipient relationship), transplant (HLA mismatch, peak panel‐reactive antibody, previous transplantation, year of transplantation), and recipient (age, sex, race/ethnicity, body mass index, cause of ESRD, and time on dialysis) risk factors. Median recipient follow‐up was 12.5 years (interquartile range 7.4–17.9, maximum 20 years). Recipients of allografts from donors who developed ESRD had increased death‐censored graft loss (74% versus 56% at 20 years; adjusted hazard ratio [aHR] 1.7; 95% confidence interval [CI] 1.5–2.0; p < 0.001) and mortality (61% versus 46% at 20 years; aHR 1.5; 95% CI 1.2–1.8; p < 0.001) compared with matched recipients of allografts from donors who did not develop ESRD. This association was similar among related, spousal, and unrelated nonspousal donors. These findings support a novel view of the mechanisms underlying donor ESRD: that of pre‐donation kidney disease. However, biopsy data may be required to confirm this hypothesis.     

Nonstandard Exception Requests Impact Outcomes for Pediatric Liver Transplant Candidates

Nonstandard exceptions requests (NSERs), in which transplant centers appeal on a case‐by‐case basis for Pediatric End‐Stage Liver Disease/Mayo End‐Stage Liver Disease points, have been highly utilized for pediatric liver transplant candidates. We evaluated whether NSE outcomes are associated with waitlist and posttransplant mortality. United Network for Organ Sharing (UNOS) Scientific Registry of Transplant Recipients data on pediatric liver transplant candidates listed in 2009–2014 were analyzed after excluding those granted automatic UNOS exceptions. Of 2581 pediatric waitlist candidates, 44% had an NSE request. Of the 1134 children with NSERs, 93% were approved and 7% were denied. For children 2–18 years at listing, NSER denial increased the risk of waitlist mortality or removal for being too sick (subhazard ratio 2.99, 95% confidence interval [CI] 1.26–7.07, p = 0.01 in multivariate analysis). For children younger than 2 years, NSER denial did not impact waitlist mortality/removal. Children with NSER approved had reduced risk of graft loss 3 years posttransplant in univariate but not multivariable analysis (odds ratio 0.73, 95% CI 0.53–1.01, p = 06). Those with NSER denial had a higher risk of posttransplant death than those with no NSER (hazard ratio 2.43, 95% CI 0.99–5.95, p = 0.05, multivariable analysis), but NSER approval did not impact posttransplant death. Further research on NSER utilization in pediatric liver transplant is needed to optimize organ allocation and outcomes for children.