Comprehensive Options for Pediatric Donation After Circulatory Death Donors

Although donor shortages have prompted increased use of livers from donors after circulatory death, data are limited on their outcomes in low-volume centers and their applicability in this setting. We retrospectively reviewed liver transplants from donors after circulatory death performed at our low-volume center over a 7-year period and identified predictors of outcomes. Between 2007 and 2014, of 196 liver transplants (mean 28/year), donations after circulatory death accounted for 31%. Patient/liver graft survival rates were similar in recipients of brain dead donor versus circulatory death donor allografts (P = .47 and P = .87 respectively): 88.4% versus 85.7%/87.7 versus 86.3% at 1 year, 78.5 versus 74.2%/76.5% versus 75.4% at 3 years, and 70.8% versus 62.0%/65.1% versus 63.7% at 5 years. Multivariable analysis identified recipients with hepatitis C virus from donors >50 years old as an independent predictor of graft and patient survival (P < .01). Biliary complications trended higher in recipients of circulatory death donor livers. Among solitary liver transplant recipients, although biliary complications adversely affected graft survival in both groups (circulatory death vs brain dead donor cohorts, P = .02 vs P = .03), patient survival was only affected in the circulatory death donor cohort (P = .01). However, when all transplants were included in graft loss modeling, presence of biliary complications significantly impacted graft survival only in recipients of livers from circulatory death donors (P < .01). Among biliary complications, ischemic cholangiopathy had the greatest impact on graft loss (P ≤ .01). Donation after circulatory death allografts could be safely used to expand the donor pool even in low-volume liver transplant centers. Outcomes were comparable to grafts from donors after brain death, although biliary complications, mainly because of ischemic cholangiopathy, had a greater effect on liver transplants from circulatory death donors. Efforts to minimize ischemic cholangiopathy could enable their greater utilization, regardless of center volume, without compromising outcomes.

Cold ischemia time (CIT) is known to impact kidney graft survival rates. We compare the impact of CIT on graft failure and mortality in circulatory death versus brain death donor kidneys and how it relates to donor age. We used the prospective Dutch Organ Transplantation Registry to include 2153 adult recipients of brain death (n = 1266) and circulatory death (n = 887) donor kidneys after static cold storage from transplants performed between 2005 and 2012. CIT was modeled nonlinearly with splines. Associations and interactions between CIT, donor type, donor age, 5-year (death-censored) graft survival, and mortality were evaluated. The median CIT was 16.2 hours (interquartile range 12.8-20), ranging from 3.4 to 44.7 hours for brain death and 4.7 to 46.6 hours for circulatory death donor kidneys. At >12 hours of CIT, we observed an increased risk of graft failure in kidneys donated after circulatory death versus after brain death. This risk rose significantly at >22 hours of CIT (hazard ratio 1.45; 95% confidence interval, 1.01-2.49; P = 0.043). Kidneys that came from 60-year-old circulatory death donors demonstrated elevated hazard risk at 19 hours of CIT, a shorter timeline than that for kidneys that came from brain death donors of the same age (hazard ratio 1.33; 95% confidence interval, 1.00-1.78; P = 0.045). The additional harmful effects of increased CIT in kidneys from circulatory-death donors were also found for death-censored graft failure but did not affect mortality rates in any significant way. The findings support the hypothesis that prolonged cold ischemia is more harmful for circulatory death donor kidneys that have already been subjected to a permissible period of warm ischemia. Efforts should be made to reduce CIT, especially for older circulatory death donor kidneys.

BackgroundLiver grafts from donation after circulatory death (DCD) donors are increasingly accepted as an extension of the organ pool for transplantation. There is little data on the outcome of liver transplantation with DCD grafts from a pediatric donor. The objective of this study was to assess the outcome of liver transplantation with pediatric DCD grafts and to compare this with the outcome after transplantation of livers from pediatric donation after brain death (DBD) donors.MethodAll transplantations performed with a liver from a pediatric donor (≤16 years) in the Netherlands between 2002 and 2015 were included. Patient survival, graft survival, and complication rates were compared between DCD and DBD liver transplantation.ResultsIn total, 74 liver transplantations with pediatric grafts were performed; twenty (27%) DCD and 54 (73%) DBD. The median donor warm ischemia time (DWIT) was 24 min (range 15–43 min). Patient survival rate at 10 years was 78% for recipients of DCD grafts and 89% for DBD grafts (p = 0.32). Graft survival rate at 10 years was 65% in recipients of DCD versus 76% in DBD grafts (p = 0.20). If donor livers in this study would have been rejected for transplantation when the DWIT ≥30 min (n = 4), the 10-year graft survival rate would have been 81% after DCD transplantation. The rate of non-anastomotic biliary strictures was 5% in DCD and 4% in DBD grafts (p = 1.00). Other complication rates were also similar between both groups.ConclusionsTransplantation of livers from pediatric DCD donors results in good long-term outcome especially when the DWIT is kept ≤30 min. Patient and graft survival rates are not significantly different between recipients of a pediatric DCD or DBD liver. Moreover, the incidence of non-anastomotic biliary strictures after transplantation of pediatric DCD livers is remarkably low.

Early national trends of lung allograft use during donation after circulatory death heart procurement in the United States

There are three categories of deceased donors of kidney transplantation in China, donation after brain death (DBD), donation after circulatory death (DCD), and donation after brain death followed by circulatory death (DBCD) donors. The aim of this study was to compare the outcomes of kidney transplantation from these three categories of deceased donors. We retrospectively reviewed 469 recipients who received deceased kidney transplantation in our hospital from February 2007 to June 2015. The recipients were divided into three groups according to the source of their donor kidneys: DBD, DCD, or DBCD. The primary endpoints were delayed graft function (DGF), graft loss, and patient death. The warm ischemia time was much longer in DCD group compared to DBCD group (18.4minutes vs 12.9minutes, P<.001). DGF rate was higher in DCD group than in DBD and DBCD groups (22.5% vs 10.2% and 13.8%, respectively, P=.021). Urinary leakage was much higher in DCD group (P=.049). Kaplan-Meier analysis showed that 1-, 2-, and 3-year patient survivals were all comparable among the three groups. DBCD kidney transplantation has lower incidences of DGF and urinary leakage than DCD kidney transplant. However, the overall patient and graft survival were comparable among DBD, DCD, and DBCD kidney transplantation.

The application of normothermic machine perfusion (NMP) machine technology as an assessment device may help to increase the utility of kidneys from uncontrolled donation after circulatory death (uDCD) donors. Here, we describe a case in which NMP perfusion characteristics were misleading and failed to predict primary nonfunction in 2 kidneys from a uDCD. The donor was a 37-y-old man who died of an intracerebral hemorrhage. Before withdrawal of life supporting treatment the donor had a cardiac arrest. He was rapidly transferred to the operating room and the abdominal organs cold perfused in situ with University of Wisconsin solution at 4°C. The first warm ischemic time was 27 min. Both kidneys appeared very poorly perfused and were further flushed on the back table with 4 L of hyperosmolar citrate solution over a period of 90 min. The appearance of both kidneys improved but they still remained patchy. The kidneys underwent a 1-h period of NMP as previously described.1,2 During NMP, the macroscopic appearance, renal blood flow, and urine output of both kidneys met our published criteria for transplantation2 (Table 1). The kidneys were transplanted into 2 separate nonsensitized recipients (Table 1). Immunological cross-matching was negative for both transplants. Both kidneys had a single renal artery and vein and these were anastomosed to the external iliac vessels. There was no intraoperative hypotension. A baseline biopsy taken from the left kidney 30 min after transplantation showed severe ischemic/reperfusion injury with almost all glomerular and peritubular capillaries filled with sludged red cells. Percutaneous needle core biopsies of both kidneys at day 8 showed infarction of the entire specimen. Computerized tomography angiography demonstrated patency of the main renal arteries and veins but diffuse poor parenchymal enhancement. In the absence of any improvement in renal function, primary nonfunction (PNF) was diagnosed in both kidneys at 3 mo. TABLE 1. - Recipient characteristics, preservation times, and normothermic machine perfusion parameters of the left and right kidney Left kidney Right kidney Recipient characteristics Gender/age Male 44 y Male 43 y Cause of ESRF APCKD Membranous GN Dialysis Predialysis Predialysis eGFR (mL/min) 9 10 HLA mismatch 1-0-1 1-0-1 Preservation times CIT (first) min 177 291 NMP min 67 60 CIT (second) min 158 433 Anastomosis min 47 55 Total CIT min 335 724 NMP parameters Macroscopic appearance 2 1 Mean RBF (mL/min/100g) 65.6 112.8 Total urine output (mL) 45 65 Oxygen consumption (mL/min/g) 36.6 48.0 Pre-NMP Post-NMP Pre-NMP Post-NMP pH 7.42 7.43 7.51 7.53 Potassium (mmol/L) 10.8 15.4 8.4 13.2 Lactate (mmol/L) 10.4 8.2 7.3 7.5 Glucose (mmol/L) 10.6 7.2 10.4 5.2 Recipient characteristics; gender/age, cause of ESRF, dialysis, eGFR, and HLA mismatch. Preservation times; CIT, NMP, second CIT, and anastomosis time. NMP parameters; macroscopic appearance (1, excellent; 2, patchy; 3, poor), mean RBF, total urine output, oxygen consumption after 60 min, prearterial and postarterial NMP levels of pH, potassium, lactate, and glucose. APCKD and membranous GN.APCKD, autosomal dominant polycystic kidney disease; CIT, cold ischemic time; eGFR, estimated glomeruli filtration rate; ESRF, end-stage renal failure; membranous GN, membranous glomerulonephritis; NMP, normothermic machine perfusion; RBF, renal blood flow. Extensive red cell plugging at revascularization led to cortical necrosis and allograft quality assessment by NMP failed to predict PNF. The young age of the donor and the short ischemic times were favorable factors. However, inadequate clearance of the microcirculation after in situ and back-table flushing is a well-described complication of prolonged warm-ischemic injury in uDCD organs.3,4 NMP theoretically offers a more accurate pretransplant viability assessment, because it restores cellular metabolism.2 We have used NMP to successfully assess and salvage kidneys from controlled donation after circulatory death donors because of inadequate clearance of the microcirculation after in situ cooling.2 This is the first report of applying the same principle to uDCD kidneys, and the adverse outcome is admonitory. The failure of NMP to predict PNF in these cases may be related to the duration and nature of the perfusion protocol. A 1-h period of NMP has been the standard in our practice and its effect on delayed graft function is currently being trialed in donation after circulatory death kidneys.5 However, cortical necrosis takes some hours to evolve and a more extended period of NMP might have been more predictive of the outcome. Furthermore, NMP conditions are designed to be protective and could mask the actual level of ischemic injury within a short timeframe. In conclusion, NMP strategies need to be further developed to reliably salvage and assess kidneys with severe ischemic injury complicated by poor clearance of the microvasculature.

ABSTRACTIntroductionUtilization of donation after circulatory death (DCD) donors in lung transplant in the United States lags when compared to other countries. We sought to evaluate geographical variation in the percentage of donation after circulatory death donors, conversion to lung transplant, agonal times, and consent for donation.MethodsWe queried the United Network for Organ Sharing database (2018–2023) to identify DCD donors and compared across organ procurement organizations (OPO). We illustrated the geographical variation in the location of transplant centers using DCDs, DCD donors used for solid organ transplant/ lung transplant, and median agonal time. Also, a special mapping was performed for the geographical difference of the refusal code utilization for declining the DCD lungs.ResultsThere were 889 DCD donors where at least one lung was used for transplant, while 13,030 (75.6%) resulted in other solid organ transplants. The utilization of DCD organs was >65% and equal across the US, while DCD transplant centers were predominantly located in 5 states. The lower utilization of DCD lungs, up to 12.7% was equally observed in each state. Over 75%, of DCDs had an agonal time ≤ 30 min in most states except South Florida, eastern Pennsylvania and Colorado/Wyoming. The map colored based on the refusal code categories also showed the geographical differences.ConclusionAs we continue to increase DCD lung utilization in the United States, better understanding of geographical barriers, adopting universal protocols in DCD organ donation and palliative care will hopefully lead to better utilization of organs from DCD donors, thereby increasing the number of transplants and decreasing organ wait times.

Retrograde flush is more protective than heparin in the uncontrolled donation after circulatory death lung donor

Background.There is limited evidence on heart and kidney transplants using donation after circulatory death (DCD) donors, especially regarding graft outcomes. However, little is known about the use of DCD donors for simultaneous heart and kidney transplants (SHKTs) compared with SHKTs using donation after brain death (DBD) donors.Methods.From May 22, 2020, to September 30, 2023, 1129 adult patients received SHKTs (DCD, N = 91 versus DBD, N = 1038), identified using the United Network for Organ Sharing database, excluding other multiorgan transplants and retransplants. A propensity score matching was performed using characteristics. Ninety-one DCD- and 273 DBD-matched cases were compared.Results.In the unmatched cohort, DCD recipients were older (DCD: 60 versus DBD: 58 y, P = 0.03), had a lower rate of dialysis at transplant (27% versus 40%, P = 0.03), and were of status 1 to 2 (43% versus 72%, P < 0.001). In the matched cohort, kidney delayed graft function (27% versus 22%, P = 0.29) was comparable, as were recipient survival (P = 0.19), heart graft survival (P = 0.19), and kidney graft survival (P = 0.17). In multivariate Cox proportional hazards analysis, donor type (DCD) was not associated with an increased risk of mortality (hazard ratio, 1.69; 95% confidence interval, 0.90-3.16; P = 0.10). Subgroup analysis showed that survival and freedom from graft failures were comparable between different modes of DCD recovery.Conclusions.SHKT using DCD donors yields comparable survival and graft outcomes to those using DBD donors. These findings may help donor selection in heart transplant candidates with kidney dysfunction.

Low-dose In Situ Perfusion With Euro-Collins Solution Is Effective for the Procurement of Marginal Kidney Grafts From Donation After Circulatory Death Donors

A large increase in the use of kidneys from donation after circulatory death (DCD) donors prompted us to examine the impact of donor type on the incidence of ureteric complications (UCs; ureteric stenosis, urinary leak) after kidney transplantation. We studied 1072 consecutive kidney transplants (DCD n=494, live donor [LD] n=273, donation after brain death [DBD] n=305) performed during 2008-2014. Overall, there was a low incidence of UCs after kidney transplantation (3.5%). Despite a trend toward higher incidence of UCs in DCD (n=22, 4.5%) compared to LD (n=10, 3.7%) and DBD (n=5, 1.6%) kidney transplants, donor type was not a significant risk factor for UCs in multivariate analysis (DCD vs DBD HR: 2.33, 95% CI: 0.77-7.03, P=.13). There was no association between the incidence of UCs and donor, recipient, or transplant-related characteristics. Management involved surgical reconstruction in the majority of cases, with restenosis in 2.7% requiring re-operation. No grafts were lost secondary to UCs. Despite a significant increase in the number of kidney transplants from DCD donors, the incidence of UCs remains low. When ureteric complications do occur, they can be treated successfully with surgical reconstruction with no adverse effect on graft or patient survival.

Transplantation of donation after circulatory death (DCD) donor hearts is gaining acceptance. However, DCD heart selection has been understandably cautious. We report a case of reconditioning a DCD heart using thoraco-abdominal normothermic regional perfusion in a 46-year-old donor who suffered irreversible brain injury following emergency type-A aortic dissection repair. The DCD heart was procured with cold preservation and directly transplanted into a 63-year-old male who was bridged to transplant with extracorporeal life support. The recipient required a brief period of mechanical circulatory support post-transplant but made a good recovery. To our knowledge, this is the first report of successful heart transplantation from such an extended criteria DCD donor.

Lung Transplantation from Donation after Circulatory Death Donors Following Portable Ex-Vivo Lung Perfusion: Post-Hoc Analysis of OCS Lung EXPAND Trial

Purpose: Utilization of donation after circulatory death (DCD) donors has the potential to decrease donor shortage in lung transplantation (LTx). This study reviews the long-term outcome of LTx from DCD donors.Methods: We included all consecutive DCD (Maastricht Category III) and all donations after brain death (DBD) donor lung transplants at our Center performed between January 2012 and February 2017. Data were analyzed comparing the two groups in regard of survival after LTx as primary outcome.Results: Median withdrawal to cardiac arrest time was 17 min (interquartile range [IQR]: 11.5–20.5). Median cardiac arrest to cold perfusion was 32 min (IQR: 24.5–36.5). Primary graft dysfunction (PGD) grade 3 at T72 occurred in three recipients. Chronic lung allograft dysfunction (CLAD) led to death in two cases. In DCD group, there was no 90-day mortality. In DCD, group 1- and 3-year survival rates were 100% and 80%. In DBD group, 1- and 3-year survival rates were 85% and 69% (p = 0.4).Conclusions: Our report confirmed the comparable outcome from DCD donors compared with DBD donors. Utility of DCD donors is a safe option to overcome donor shortage.

Outcomes after simultaneous pancreas–kidney transplantation from donation after circulatory death donors: A UK registry analysis