Outcomes of Kidney Transplants from Donors after Circulatory Death with Acute Kidney Injury: A Systematic Review

Over the decade between 2003 and 2012, the UK has seen major changes in how organ donation and transplantation is delivered. The number of deceased organ donors has increased from 709 (12.0 per million population [pmp]) to 1,164 (18.3 pmp); this increase has been predominantly a result of an increase in donors after circulatory death (DCD) (from 1.1 pmp to 7.9 pmp) while the numbers of donors after brain death (DBD) has remained broadly stable (around 10.5 pmp). The donor population has become older (from 14% 60 years or over to 35%) and heavier (from 14% with body mass index >=30 kg/m2 to 23%). Despite these changes in demographic factors, the number of organs retrieved from DBD donors has risen from a mean of 3.6 to 4.0 per donor and for DCD donors from 2.2 to 2.6. The number of transplants in adults in 2012 was 2,709 (967 DBD, 708 DCD, and 1,034 living) for kidney alone, 246 pancreas (including 172 kidney and pancreas), 792 (611 DBD, 142 DCD, 36 living, and 3 domino) for liver, 136 for heart only, and 179 (145 DBD and 34 DCD) for lung only. Median waiting times to transplant for adult patients were 1,167, 339, 141, 293, and 311 days, respectively. The proportion of adult non-urgent registrants in 2009 (2007 for kidneys) who were removed from the waiting list or died awaiting a graft within 1 year was 3% for kidneys, 6% for pancreas, 19% for liver, 27% for heart, and 24% for lung. Outcomes after solid organ transplants are improving; for adult patients grafted between 2003 and 2005, 5-year graft survival for kidney is 84% (DBD), 87% (DCD), and 92% (living donor), for simultaneous kidney and pancreas 72%, and for pancreas alone 50% (DBD). Five-year patient survival for liver is 77% (DBD) and 68% (DCD), heart 67%, and lung 52% (DBD). Although rates of organ donation and transplantation have increased in the UK, this has been almost solely because of a rise in DCD donation. Although donor age and weight is increasing, graft survival has generally improved. Despite a recent fall in the number of patients on the transplant waiting list, there remains a significant gap between the need for transplantation and the number of organs available from deceased and living donors. The implementation of a new strategy following the recommendations of the Organ Donation Task Force in 2008 has had a major impact in bringing together clinicians involved in both organ donation and transplantation, and these changes and clinical enthusiasm have been instrumental in achieving success. With an emphasis on the need to increase the family consent rate for organ donation, which has failed to show any improvement over the last 5 years, a new UK strategy for organ donation and transplantation, introduced in 2013, will further increase organ transplantation in the UK.

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

Ex vivo normothermic machine perfusion (NMP) of donor kidneys prior to transplantation provides a platform for direct delivery of cellular therapeutics to optimize organ quality prior to transplantation. Multipotent Adult Progenitor Cells (MAPC® ) possess potent immunomodulatory properties that could minimize ischemia reperfusion injury. We investigated the potential capability of MAPC cells in kidney NMP. Pairs (5) of human kidneys, from the same donor, were simultaneously perfused for 7 hours. Kidneys were randomly allocated to receive MAPC treatment or control. Serial samples of perfusate, urine, and tissue biopsies were taken for comparison. MAPC-treated kidneys demonstrated improved urine output (P=.009), decreased expression of injury biomarker NGAL (P=.012), improved microvascular perfusion on contrast-enhanced ultrasound (cortex P=.019, medulla P=.001), downregulation of interleukin (IL)-1β (P=.050), and upregulation of IL-10 (P<.047) and Indolamine-2, 3-dioxygenase (P=.050). A chemotaxis model demonstrated decreased neutrophil recruitment when stimulated with perfusate from MAPC-treated kidneys (P<.001). Immunofluorescence revealed prelabeled MAPC cells in the perivascular space of kidneys during NMP. We report the first successful delivery of cellular therapy to a human kidney during NMP. Kidneys treated with MAPC cells demonstrate improvement in clinically relevant parameters and injury biomarkers. This novel method of cell therapy delivery provides an exciting opportunity to recondition organs prior to transplantation.

Organ donation after circulatory death (DCD) was reintroduced in Switzerland in 2011 and accounts for a third of deceased organ donors today. Controversy persists if DCD transplants are of similar quality to transplants following donation after brain death (DBD), mainly due to warm ischaemia time DCD organs are exposed to. We compared DCD with DBD in Switzerland. Data on deceased adults who were referred to and approved for organ donation from 1 September 2011 to 31 December 2019 were retrospectively analysed (217 DCD, 840 DBD donors). We compared DCD and DBD donor/organ characteristics, transplant rates of lungs, liver, kidneys, and pancreas, and early liver and kidney graft function in the recipient. The effect of DCD/DBD on transplant rates (organ transplanted or not) and 72-hour recipient graft function (moderate/good vs delayed graft function / organ loss) was analysed using multivariable logistic regression. Among utilised DCD donors, we analysed the effect of functional warm ischaemia time (FWIT) and donor age on 72-hour post-transplant liver and kidney graft function, also using multivariable logistic regression. DCD donors were more often male (64.5% vs 56.8% p = 0.039), presented with heart disease (36.4% vs 25.5%, p <0.001), were resuscitated before hospital admission (41.9% vs 30.7%, p = 0.006), and died from anoxia (41.9% vs 23.9%). Kidney function before transplantation was comparable, lung, liver and pancreas function were poorer in DCD than DBD. Eighty-one and 91% of approved DCD and DBD donors were utilised (p <0.001). Median FWIT in DCD was 29 minutes (interquartile range 25-35). DCD transplant rates ranged from 4% (pancreas) to 73% (left kidney) and were all lower compared with DBD. Seventy-two-hour liver graft function was comparable between DCD and DBD (94.2% vs 96.6% moderate/good, p = 0.199). DCD kidney transplants showed increased risk of delayed graft function or early organ loss (odds ratios 8.32 and 5.05; 95% confidence intervals CI 5.28-13.28 and 3.22-7.95; both p <0.001, for left and right kidney transplants, respectively). No negative effect of prolonged FWIT or higher donor age was detected. Despite less favourable donor/organ characteristics compared with donation after brain death, donation after circulatory death donors are increasingly referred and today provide an important source for scarce transplants in Switzerland. We identified a higher risk for delayed graft function or early organ loss for DCD kidney transplants, but not for DCD liver transplants. When carefully selected and allowed for other risk factors in organ allocation, prolonged functional warm ischaemia time or higher age in donation after circulatory death does not seem to be associated with impaired graft function early after transplantation.

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

Kidney donation after circulatory death (DCD): state of the art

Donation after circulatory death (DCD) kidney transplantation has acceptable renal allograft survival in adults but there are few data in pediatric recipients. The aim of this study was to determine renal allograft outcomes for pediatric recipients of a DCD kidney. Data were collected from the UK Transplant Registry held by National Health Service Blood and Transplant. Kidney transplants performed for pediatric recipients (age, <18 years) in the United Kingdom from 2000 to 2014 were separated into DCD, donation after brain death (DBD), and living donor (LD) transplants, analyzing 3-year patient and renal allograft survival. One thousand seven hundred seventy-two kidney only transplants were analyzed. Twenty-one (1.2%) of these were from DCD donors, 955 (53.9%) from DBD donors, and 796 (44.9%) from LDs. Patient survival is 100% in the DCD group, 98.7% in the DBD group, and 98.9% in the LD group. Three-year renal allograft survival was 95.2% in the DCD group, 87.1% in the DBD group, and 92.9% in the LD group. There was no significant difference in 3-year renal allograft survival between the DCD and DBD groups (P = 0.42) or DCD and LD groups (P = 0.84). For DCD, the primary nonfunction rate was 5% and delayed graft function was 25%. Children receiving a DCD kidney transplant have good renal allograft survival at 3-year follow-up, comparable to those receiving a kidney from a DBD donor or a LD. This limited evidence encourages the use of selected DCD kidneys in pediatric transplantation, and DCD allocation algorithms may need to be reviewed in view of this.

BackgroundStandard-criteria donation after circulatory death (DCD) kidney transplants (KTx) have higher primary nonfunction, delayed graft function (DGF), and rejection rates than age-matched donation after brain death (DBD) but similar graft survival. Data on expanded-criteria DCD are conflicting and many centers remain concerned regarding their use.MethodsIn this single-center observational study with 5-year follow-up, we analyzed data from 112 primary DCD Maastricht category-III single KTx receiving similar organ preservation and maintenance immunosuppression. Patients were sorted as young DCD (donor <60 years, 72 recipients) or old DCD (donor ≥60 years, 40 recipients). Old DCD outcomes were compared with young DCD and to a DBD control group (old DBD, donor ≥60 years, 40 recipients).ResultsAfter 5 years, old DCD showed lower patient survival (66% vs 85%; P = 0.014), death-censored graft survival (63% vs 83%; P = 0.001), and Modification of Diet in Renal Disease estimated glomerular filtration rate (34, 27.0-42.0 mL/min per 1.73 m2 vs 45.0, 33.0-58.0 mL/min per 1.73 m2; P = 0.021) than young DCD with higher DGF (70% vs 47.2%; P = 0.029) and graft thrombosis (12.5% vs 1.4%; P = 0.021). Comparison between old DCD and old DBD showed similar 5-year patient survival (66% vs 67%; P = 0.394) and death-censored graft survival (63% vs 69%; P = 0.518) but higher DGF (70% vs 37.5%; P = 0.007) and lower estimated glomerular filtration rate (34, 27.0-42.0 mL/min per 1.73 m2 vs 41, 40.0-42.0 mL/min per 1.73 m2; P = 0.029). Multivariate Cox regression analysis showed that donor 60 years or older (hazard ratio, 3.135; 95% confidence interval, 1.716-5.729; P < 0.001) and induction with anti–IL2-receptor-α monoclonal antibody (hazard ratio, 0.503; 95% confidence interval, 0.269-0.940, P = 0.031 in favor of induction with rabbit antithymocyte globulin) are independent predictors of transplant loss.ConclusionsOverall, single KTx from DCD Maastricht category-III donors 60 years or older have inferior outcomes than KTx from donors younger than 60 years. Comparison with age-matched DBD showed similar patient and graft survivals. However, the discrepancy in graft function between DCD and DBD deserves further investigation.

The donor hypoperfusion phase before asystole in renal transplants from donors after circulatory death (DCD) has been considered responsible for worse outcomes than those from donors after brain death (DBD). We included 10 309 adult renal transplants (7128 DBD and 3181 DCD; 1 January 2010-31 December 2016) from the UK Transplant Registry. We divided DCD renal transplants into groups according to hypoperfusion warm ischaemia time (HWIT). We compared delayed graft function (DGF) rates, primary non-function (PNF) rates and graft survival among them using DBD renal transplants as a reference. The DGF rate was 21.7% for DBD cases, but ∼40% for DCD cases with HWIT ≤30 min (0-10 min: 42.1%, 11-20 min: 43%, 21-30 min: 38.4%) and 60% for DCD cases with HWIT >30 min (P < 0.001). All DCD groups showed higher DGF risk than DBD renal transplants in multivariable analysis {0-10 min: odds ratio [OR] 2.686 [95% confidence interval (CI) 2.352-3.068]; 11-20 min: OR 2.531 [95% CI 2.003-3.198]; 21-30 min: OR 1.764 [95% CI 1.017-3.059]; >30 min: OR 5.814 [95% CI 2.798-12.081]}. The highest risk for DGF in DCD renal transplants with HWIT >30 min was confirmed by multivariable analysis [versus DBD: OR 5.814 (95% CI 2.798-12.081) versus DCD: 0-10 min: OR 2.165 (95% CI 1.038-4.505); 11-20 min: OR 2.299 (95% CI 1.075-4.902); 21-30 min: OR 3.3 (95% CI 1.33-8.197)]. No significant differences were detected regarding PNF rates (P = 0.713) or graft survival (P = 0.757), which was confirmed by multivariable analysis. HWIT >30 min increases the risk for DGF greatly, but without affecting PNF or graft survival.

Donation after circulatory death (DCD) heart procurement has increased, but concerns remain about the effect of simultaneous heart and lung procurement, particularly with thoracoabdominal normothermic regional perfusion (TA-NRP), on the use of DCD lungs. Previous analyses exclude critical donor factors and organ nonuse, and rapidly rising DCD use may bias comparisons to historical controls. To use validated risk-adjusted models to assess whether DCD heart procurement via TA-NRP and direct procurement is associated with lung use. This retrospective cohort study involved adult DCD donors between January 1, 2019, and September 30, 2024, listed in the Scientific Registry of Transplant Recipients (SRTR). The SRTR deceased donor yield model was used to develop an observed to expected (O:E) yield ratio of lung use obtained through DCD among 4 cohorts: cardiac DCD donors vs noncardiac DCD donors and cardiac DCD donors undergoing TA-NRP vs direct procurement. Temporal trends in O:E ratios were analyzed with the Cochran-Armitage test. The O:E ratios of DCD lung use. Among 24 431 DCD donors (15 878 [65.0%] male; median [IQR] age, 49.0 [37.0-58.0] years), 22 607 were noncardiac DCD (14 375 [63.6%] male; median [IQR] age, 51.0 [39.0-58.0] years) and 1824 were cardiac DCD (1503 [82.4%] male; median [IQR] age, 32.0 [26.0-38.0] years) donors; noncardiac DCD donors were more likely to be smokers (6873 [30.4%] vs 227 [12.4%]; P < .001). Among cardiac DCD donors, 325 underwent TA-NRP, while 712 underwent direct procurement. TA-NRP donors had shorter median (IQR) lung ischemic times (6.07 [4.38-9.56] hours vs 8.12 [6.16-12.00] hours; P < .001) and distances to recipient hospitals (222 [9-626] nautical miles vs 331 [159-521] nautical miles; P = .050) than direct procurement donors. Lung use was higher among cardiac DCD donations compared with noncardiac DCD donations (16.7% vs 4.4%, P < .001). Within the cardiac DCD cohort, lung use was similar between TA-NRP and direct procurement (19.1% vs 18.7%; P = .88) cohorts. Both noncardiac DCD and cardiac DCD donors had observed lung yields greater than expected (O:E, 1.29 [95% CI, 1.21-1.35] and 1.79 [95% CI, 1.62-1.96]; both P < .001), although cardiac DCD yield was significantly higher than noncardiac DCD yield (P < .001). Both TA-NRP and direct procurement lung yields were greater than expected (O:E, 2.00 [95% CI, 1.60-2.43] and 1.77 [95% CI, 1.52-1.99]; both P < .001) but were not significantly different from each other (P = .83). The O:E ratios did not change significantly over time across all cohorts. Among recipients, the TA-NRP cohort experienced significantly better 90-day mortality (0 of 62 vs 9 of 128 patients [7.0%]; P = .03) and overall survival (4 of 62 patients [6.5%] vs 21 of 128 patients [16.4%]; P = .04) rates compared with the direct procurement cohort. In this cohort study of DCD donors, concomitant heart procurement provided better-than-expected rates of lung use as assessed with validated O:E use ratios regardless of procurement technique. The findings also suggest a survival benefit with improved 90-day and overall survival rates for the TA-NRP cohort compared with the direct procurement cohort. Policies should be developed to maximize the benefits of these donations.

There is limited experience transplanting kidneys from either expanded criteria donors (ECD) or donation after circulatory death (DCD) deceased donors with terminal acute kidney injury (AKI). AKI kidneys were defined by a donor terminal serum creatinine level>2.0mg/dL whereas non-ideal deceased donor (NIDD) kidneys were defined as AKI/DCD or AKI/ECDs. From February 2007 to March 2023, we transplanted 266 single AKI donor kidneys including 29 from ECDs, 29 from DCDs (n=58 NIDDs), and 208 from brain-dead standard criteria donors (SCDs). Mean donor age (43.7 NIDD vs. 33.5 years SCD), KDPI (66% NIDD vs. 45% SCD), and recipient age (57 NIDD vs. 51 years SCD) were higher in the NIDD group (all p<.01). Mean waiting times (17.8 NIDD vs. 24.2 months SCD) and dialysis duration (34 NIDD vs. 47 months SCD) were shorter in the NIDD group (p<.05). Delayed graft function (DGF, 48%) and 1-year graft survival (92.7% NIDD vs. 95.9% SCD) was similar in both groups. Five-year patient and kidney graft survival rates were 82.1%versus 89.9% and 82.1%versus 75.2% (both p=NS) in the NIDD versus SCD groups, respectively. The use of kidneys from AKI donors can be safely liberalized to include selected ECD and DCD donors.

Lung transplantation using controlled donation after circulatory death donors: Trials and tribulations

Introduction: Organs from donation after circulatory death (DCD) donor are increasingly being used to expand the donor pool. What are the outcomes of simultaneous pancreas-kidney transplants (SPKTx) utlizing DCD donors? Methods: A single centre, retrospective study was performed of 129 consecutive systemic-enteric drained SPKTx performed from 18/2/2006 to 10/10/2011. The SPKTx from DCD (n=15) were compared to DBD organs (n=114). The median follow-up was significantly shorter in the DCD group compared to the donation after brain death (DBD) group (17 months vs. 40 months). Therefore, actuarial survival analysis was done, and 2 year outcomes are reported. Results: DCD donors had a greater proportion whose cause of death was trauma (57% DCD vs. 22% DBD, p=0.005), and DCD donors were younger compared to the DBD donors (mean age 29 yrs DCD vs. 34 yrs DBD, p=0.1). Other donor, recipient and transplant characteristics compared were similar between the 2 groups. There was no significant difference between the 2 groups in the 2 year actuarial patient survival (100% DCD vs. 97% DBD), death-censored pancreas survival (91% DCD vs. 92% DBD), and death-censored kidney allograft survival (96% vs. 100%, all p=NS). The rates of kidney delayed graft function were similar (27% DCD vs. 25% DBD, p=NS). Analysis of other outcomes showed no significant difference in the incidence of 1st year biopsy-proven acute rejections (27% each), peripancreatic fluid collections (27% DCD vs. 18% DBD), pancreatic fistula (12% each), proven duodenal stump leak (0 DCD vs. 4% DBD), graft pancreatitis (27% DCDvs. 36% DBD), graft thrombosis (0 DCD vs. 2% DBD) and major bleeding (7% each). Although the overall infection rates were similar (67% DCD vs. 56% DCD), there was slightly higher incidence of intra-abdominal sepsis (27% DCD vs. 12% DBD, p=0.1) in the DCD group. Further analysis showed that all cases of the intra-abdominal sepsis in the DCD group were peripancreatic fluid collections that were infected. There was no obvious duodenal stump leak in any of these 4 collections. Conclusion: The outcomes of DCD SPKTx were seen to be excellent, and comparable with the DBD transplants. There was a slightly increased incidence of infected intraabdominal collections in the DCD group, which could possibly be related to contamination from the rapid process involved in the DCD organ retrieval. However, our numbers are small, and would benefit from a larger series analysis for a definite conclusion.

Background Large scale registry studies have demonstrated that donation after circulatory death (DCD) and donation after brain death (DBD) donor kidney transplants have comparable graft survival. However, donor race, a known risk for graft survival, has not been considered in these analyses. Additionally, there is growing evidence to suggest potential racial differences in renal ischaemic tolerance. This study aims to address this knowledge gap, evaluating whether donor race modifies the impact of DCD donation on graft survival using a large, multi-centre database. Methods A retrospective observational analysis was performed using 261,634 kidney transplant recipients from the UNOS/OPTN database (1987 - 2020), stratified by donor race. Risk-adjusted outcomes were assessed by multivariate cox analysis and visualized using Kaplan-Meier survival curves. Results Donor race significantly modified the effect of DCD donation on graft survival. Black donor DCD recipients experienced improved graft survival at 5 (HR 0.89, 95% CI 0.8-1.0, p &amp;lt; 0.05), 10 (HR 0.9, 95% CI 0.82-0.99, p &amp;lt; 0.05) and 15 years (HR 0.92, 95% CI 0.84-1.0, p &amp;lt; 0.05) compared to DBD. White donor DCD recipients experienced worse graft survival at 15 years (HR 1.08, 95% CI 1.04-1.11, p &amp;lt; 0.001), with no differences at 5 and 10 years. Conclusion DCD donation was associated with improved long-term graft survival compared to DBD in recipients of kidneys from Black donors, while recipients of DCD kidneys from White donors experienced reduced long-term graft survival compared to DBD. This highlights a potential role of donor race in modifying the effects of DCD donation on graft survival.

Effect of delayed graft function on longer-term outcomes after kidney transplantation from donation after circulatory death donors in the United Kingdom: A national cohort study