Donation After Cardiac Death Donors Research Articles

Should advanced donor age be a deterrent in the utilization of grafts from donation after cardiac death in deceased donor liver transplantation? The Toronto experience.

Advanced donor age paired with donation after cardiac death (DCD) increases the risk of transplantation, precluding widespread use of grafts from such donors worldwide. Our aim was to analyze outcomes of liver transplantation using grafts from older DCD donors and donation after brain death (DBD) donors. Patients who underwent liver transplantation using grafts from deceased donors between January 2016 and December 2021 were included in the study. Short-and long-term outcomes were analyzed for 4 groups of patients: those who received DCD and DBD grafts from younger (< 50 yr) and older (≥ 50 yr) donors. Of the 807 patients included in the analysis, 44.7% (n = 361) of grafts were received from older donors, with grafts for older DCD donors comprising 4.7% of the total cohort (n = 38). Patients who received grafts from older donors had a lower incidence of biliary strictures than those who received grafts from younger donors (7.9% v. 20.0% for DCD donation, p = 0.14, and 4.9% v. 6.8% for DBD donation, p = 0.34), with a significantly lower incidence of ischemic-type biliary strictures in patients who received grafts from older versus younger DCD donors (2.6% v. 18.0%, p = 0.04). There was no difference in 1- and 3-year graft survival rates among patients who received grafts from older and younger DCD donors (92.1% v. 90.8% and 80.2% v. 80.9%, respectively) and those who received grafts from older and younger DBD donors (90.1% v. 93.2% and 85.3% v. 84.4%, respectively) (p = 0.85). Pretransplantation admission to the intensive care unit (hazard ratio [HR] 9.041, p < 0.001) and nonalcoholic steatohepatitis (HR 2.197, p = 0.02) were found to significantly affect survival of grafts from older donors. Donor age alone should not be the criterion to determine the acceptability of grafts in liver transplantation. With careful selection criteria, older DCD donors could make a valuable contribution to expanding the liver donor pool, with grafts that produce comparable results to those obtained with standard-criteria grafts.

Transplant Candidate Outcomes After Declining a DCD Liver in the United States.

In the context of the organ shortage, donation after circulatory death (DCD) provides an opportunity to expand the donor pool. Although deceased-donor liver transplantation from DCD donors has expanded, DCD livers continue to be discarded at elevated rates; the use of DCD livers from older donors, or donors with comorbidities, is controversial. Using US registry data from 2009 to 2020, we identified 1564 candidates on whose behalf a DCD liver offer was accepted ("acceptors") and 16 981 candidates on whose behalf the same DCD offers were declined ("decliners"). We characterized outcomes of decliners using a competing risk framework and estimated the survival benefit (adjusted hazard ratio [95% confidence interval]) of accepting DCD livers using Cox regression. Within 10 y of DCD offer decline, 50.9% of candidates died or were removed from the waitlist before transplantation with any type of allograft. DCD acceptors had lower mortality compared with decliners at 10 y postoffer (35.4% versus 48.9%, P < 0.001). After adjustment for candidate covariates, DCD offer acceptance was associated with a 46% reduction in mortality (0.54 [0.49-0.61]). Acceptors of older (age ≥50), obese (body mass index ≥30), hypertensive, nonlocal, diabetic, and increased risk DCD livers had 44% (0.56 [0.42-0.73]), 40% (0.60 [0.49-0.74]), 48% (0.52 [0.41-0.66]), 46% (0.54 [0.45-0.65]), 32% (0.68 [0.43-1.05]), and 45% (0.55 [0.42-0.72]) lower mortality risk compared with DCD decliners, respectively. DCD offer acceptance is associated with considerable long-term survival benefits for liver transplant candidates, even with older DCD donors or donors with comorbidities. Increased recovery and utilization of DCD livers should be encouraged.

SP5.10 Is there a difference in Survival Outcomes of Dual Kidney Transplants (DKTs) of Allografts Procured from DCD versus DBD Donors in absence of a Dedicated National Pathology Service? A Propensity Score Analysis of UK Transplant Registry. An Epidemiology in Transplant Study Group (ETrSG) Initiative

Abstract Background Dual kidney transplants (DKTs) are generally from supra-marginal or small-for-size kidneys that are implanted to provide optimum total nephron-mass. Glomerulosclerosis Pathology Scoring is used globally to guide whether single or DKT are indicated for transplant. Additionally, there are reported concerns regarding donation after cardiac death (DCD) transplant outcomes’ inferiority to donation after brain death (DBD) transplants but there are no reported survival outcomes of DKT procured from DCD v/s DBD donors. Aim This study aims to research if there is a difference in survival outcomes of DKTs of allografts procured from DCD versus DBD Donors in the UK. Methods In this exploratory analysis, adults who underwent DKT in the UK between Jan 1, 2000, and December 31, 2019, were identified in the NHSBT-Transplant registry data. Post-transplantation graft survival at 1&amp; 3 years was assessed with cox-regression analysis, with propensity scores being used to control for selection bias. Results 51,961 renal transplants were reported to NHSBT during the study period, of whom 525 were DKT. After confounders were controlled for with propensity scores, no significant differences in survival outcomes were found between DCD and DBD transplants. Region of Transplant (OR 1.6, 1.0-2.5; p=0.02), transplant post-Year-2011 (OR 3.0, 1.7-5.2; p&amp;lt;0.00), and non-diabetic donors (OR 2.1, 1.1-3.9, p=0.009) were associated with better graft survival, while DBD transplants were associated with low delayed graft function rates (OR 0.4, 0.27 - 0.59; p&amp;lt;.001). Conclusions Survival outcomes of DKT procured from DCD versus DBD donors are equivalent. These results are admirable as the UK does not have a dedicated National-Pathology-Service to report pre-transplant renal biopsies.

SP3.1 80 patient series from UK renal transplant centre shows extended criteria deceased donor transplants are associated with a poorer graft function but at no increased risk of graft loss after 1 year

Abstract Aims Between 12/2018 – 12/2021 our centre performed 163 deceased donor transplants. 30.7% of these utilised organs from so-called extended criteria donors (ECD). ECD [originally in context of donation after brain death (DBD), but later used also for donation after cardiac death (DCD)] refers to donors &amp;gt;60yo; or &amp;gt;50yo with ≥2 of hypertension / death from CVA / Cr &amp;gt;133. We wanted to assess outcomes in ECD transplant recipients and compare with outcomes of our standard donor (SCD) recipients. Methods Retrospective analysis of 40 ECD transplants (12/2018- 12/2021) and control group of 40 age-matched (overall mean age 58.2) SCD recipients with 12 month follow up. Results The groups were comparable regarding proportion of DCD donors (ECD 62.5%, SCD 50%; X2= 1.270 p=0.260). Although rate of delayed graft function (DGF) was higher in the ECD group, this was not statistically significant (ECD: 62.5%, SCD:47.5%; X2=1.257 p=0.262). There was, however a difference in creatinine at discharge (median ECD:390; SCD:221; U= 1018.500; p=0.036) and in EGFR at 1 year (mean ECD:39.62; SCD: 54.3; t=-3.780 p&amp;lt;0.001). There was no difference in incidence of graft loss (ECD:0%; SCD:2.5%; X2=1.013, p=0.314) or mortality (ECD:5.0%; SCD:7.5%; X2=0.213, p=0.644). There was no difference in index length of stay (median ECD:6; SCD: 6; U=928.000 p=0.212), or total readmissions (median ECD:2.5; SCD:2.0; U=902.500 p=0.319). Conclusions In our sample incidence of DGF was similar between the two groups. ECD recipients had poorer graft function at 1 year but there was no evidence of increased risk of graft loss at 1 year.

Pancreas transplantation with grafts obtained from donation after cardiac death or donation after brain death results in comparable outcomes

IntroductionPancreas organ shortages and long recipient waitlist times are critical components that limit recipients from receiving a pancreas transplant. Over the last decade, our center has been using donation after cardiac death (DCD) donors as an adjunct to donation after brain death (DBD) donors to expand the organ pool. The aim of this study was to compare recipient and graft survival between DCD and DBD recipients.MethodsA retrospective single center propensity matched analysis (2011–2020) of 32 DCD vs 96 DBD pancreas transplants was performed.Results8-year recipient survival was similar between DCD and DBD groups (87.4% vs 92.7%, p=0.35) as was simultaneous kidney and pancreas transplant (SPK) 8-year kidney (88.9 vs 96.9%, p=0.219) and pancreas graft survival (77.4% vs 86.7%, p=0.344). There was no difference in vascular thrombosis rate between DCD and DBD pancreas grafts (3.1% vs 7.3%, p=0.73). DCD kidneys had a higher rate of DGF vs DBD kidneys (28.1% vs 6.3%, p=0.004), without any significant difference in long term kidney failure (12.5% vs 8.3%, p=0.5).DiscussionRecipients of DCD grafts demonstrate equivalent long-term patient and graft survival compared to DBD recipients for pancreas transplantation. Increased utilization of well selected DCD donors is a safe strategy to increase the donor pool.

Risk factors for BK virus infection in DCD donor kidney transplant recipients.

BK virus infection after kidney transplantation can negatively impact the prognosis of patients. However, current risk factor analyses primarily focus on BK virus nephropathy, while BK viruria and BK viruria progressing to BK viremia receive less attention. This study aims to analyze the risk factors associated with BK viruria and BK viruria progressing to BK viremia in recipients of donation after cardiac death (DCD), with the goal of facilitating early intervention. Donor characteristics and clinical data of recipients before and after transplantation were evaluated, and logistic univariate and multivariate analyses were performed to determine the risk factors associated with BK viruria and the progression of BK viruria to BK viremia. Additionally, machine learning techniques were employed to identify the top five features associated with BK viruria evolving into BK viremia. During a median follow-up time of 1,072 days (range 739-1,418), 69 transplant recipients (15.6% incidence rate) developed BK viruria after transplantation, with 49.3% of cases occurring within 6 months post-transplantation. Moreover, 19 patients progressed to BK viremia. Donor age [OR: 1.022 (1.000, 1.045), p = 0.047] and donor procalcitonin (PCT) levels [0.5-10 ng/ml; OR: 0.482 (0.280, 0.828), p = 0.008] were identified as independent risk factors for BK viruria. High BK viruria [OR: 11.641 (1.745, 77.678), p = 0.011], recipient age [OR: 1.106 (1.017, 1.202), p = 0.018], and immunoinduction regimen [ATG; OR: 0.063 (0.006, 0.683), p = 0.023] were independent risk factors for BK viruria progressing to BK viremia. Machine learning analysis confirmed the importance of high BK viruria, recipient age, and immunoinduction regimen (ATG) in predicting the progression of BK viruria to BK viremia. The development and progression of BK virus in DCD kidney transplant recipients is influenced by multiple factors. Early intervention and treatment could potentially extend the lifespan of the transplanted organ.

Circulating exosomes from brain death and cardiac death donors have distinct molecular and immunologic properties: A pilot study.

Comparison of donation after brain death (DBD) and donation after cardiac death (DCD) lung tissue before transplantation have demonstrated activation of pro-inflammatory cytokine pathway in DBD donors. The molecular and immunological properties of circulating exosomes from DBD and DCD donors were not previously described. We collected plasma from 18 deceased donors (12 DBD and six DCD). Cytokines were analyzed by 30-Plex luminex Panels. Exosomes were analyzed for liver self-antigen (SAg), Transcription Factors and HLA class II (HLA-DR/DQ) using western blot. C57BL/6 animals were immunized with isolated exosomes to determine strength and magnitude of immune responses. Interferon (IFN)-γ and tumor necrosis factor-α producing cells were quantified by ELISPOT, specific antibodies to HLA class II antigens were measured by ELISA RESULTS: We demonstrate increased plasma levels of IFNγ, EGF, EOTAXIN, IP-10, MCP-1, RANTES, MIP-β, VEGF, and interleukins - 6/8 in DBD plasma versus DCD. MiRNA isolated from exosome of DBD donors demonstrated significant increase in miR-421, which has been reported to correlate with higher level of Interleukin-6. Higher levels of liver SAg Collagen III (p=.008), pro-inflammatory transcription factors (NF-κB, p<.05; HIF1α, p=.021), CIITA (p=.011), and HLA class II (HLA-DR, p=.0003 and HLA-DQ, p=.013) were detected in exosomes from DBD versus DCD plasma. The circulating exosomes isolated from DBD donors were immunogenic in mice and led to the development of Abs to HLA-DR/DQ. This study provides potential new mechanisms by which DBD organs release exosomes that can activate immune pathways leading to cytokine release and allo-immune response.

Total Cell-Free DNA as a Noninvasive Biomarker of a Delayed Graft Function After Kidney Transplantation From Donors After Cardiac Death

Because of the organ shortage, donation after cardiac death (DCD) kidney transplantation (KTx) is an alternative way of achieving KTx using brain-dead donors (BDs). Although the prognosis of DCD-KTx is improving, the graft suffers from delayed graft function (DGF), the management of which is essential. With progress in understanding the characteristics of cell-free DNA (CF-DNA), we consider plasma total CF-DNA (tCF-DNA) to be a useful biomarker for predicting DGF in DCD-KTx. Consecutive patients from living donors (LDs; n=9), BDs (n=8), or DCD donors (n=13) were enrolled. Plasma samples were collected after KTx and on postoperative days 3 and 5. CF-DNA was isolated, and tCF-DNA was quantified using the TapeStation 2200 software program. The tCF-DNA levels after BD-KTx and DCD-KTx were higher than those after LD-KTx (LD, 78 ± 27 (ng/mL); BD, 99 ± 20; DCD, 150 ± 23); the difference between DCD-KTx and LD-KTx was statistically significant (P < .05). The tCF-DNA levels declined at postoperative day 5 (LD, 45 ± 10; BD, 51 ± 11; DCD, 66 ± 13). tCF-DNA levels were significantly increased in patients with DGF after KTx (DGF, 139 ± 22; immediate function, 91 ± 18; P < .05). The tCF-DNA level was correlated with the duration of DGF (r=0.5825, P < .05). Although the mechanism underlying DNA release from transplanted grafts into the recipient circulation remains unclear, cell death by apoptosis or necrosis and the active secretion of the immune system may play important roles in DGF. These data suggest that monitoring tCF-DNA may help predict graft recovery after DCD-KTx.

What's in a name? Higher risks with donation after cardiac death than public health service increased risk livers

Background: Public health service increased risk donor(IRD) and donation after cardiac death (DCD) livers are utilized to address the organ shortage in liver transplantation, particularly during the opioid epidemic. “Increased risk donor” terminology implies greater risk than DCD by its name, but without direct risk comparison.Objective: The aim of this study was to examine the risks of accepting IRD livers compared to DCD livers during the opioid epidemic.Methods: Retrospective, single center study of 92 recipients of IRD donors and 21 DCD donors(22% and 5% of adult transplants) between 1/2013-5/2017. Median post transplant follow-up was 2.6 years. The primary outcome was the composite of post-transplant risks likely to be greatest in IRD donor and DCD livers, namely, donor viral transmission (HBV, HCV, HIV) and ischemic cholangiopathy. Secondary outcomes were patient and graft survival, biopsy-proven rejection, CMV and EBV viremia. Categorical variables were analyzed using chi square and continuous variables Kruskal-Wallis techniques. Propensity score matched sensitivity analysis was conducted using logistic regression. Cox proportional hazard regression models were used for survival analyses.Results: Ischemic cholangiopathy and graft failure leading to retransplantation occurred in 40% and 14% of DCD recipients but did not occur among IRD recipients(p<0.0001). There were no occurrences of HBV, HCV, HIV transmission. Survival was similar between DCD and IRD groups(90% vs 84% respectively, p=0.23).Conclusion Despite its name, increased risk donors are less risky than DCD livers given lower rates of ischemic cholangiopathy and retransplantation, supporting the recent decision to rename this group of donors to encourage utilization.

Organ donation after cardiac death in Japan

In Japan, since the revision of the Organ Transplant Law in July 2010, donation after brain death (DBD) has increased, while donation after cardiac death (DCD), which has been mainly used by kidney transplantation, has decreased. The number of DCD donors decreased from 98 in 2009 to 28 in 2019. There is no clear reason for the decrease in DCD donors. Furthermore, since 2020, there has been a marked decrease in DCD due to the influence of the COVID-19 pandemic. On the other hand, the outcomes after kidney transplantation from DCD donors are improving year by year. The outcomes of kidney transplantation from DCD donors in Japan are comparable to those of kidney transplantation from DBD donors in Western countries. In order to further improve transplantation outcomes from DCD donors, the clinical introduction of continuous machine perfusion preservation technology, for the purpose of reducing ischemic reperfusion injury, is expected in Japan.

Long‐term outcomes of pediatric liver transplantation using organ donation after circulatory death: Comparison between full and reduced grafts

The shortage of donors' livers for pediatric recipients inspired the search for alternatives including donation after cardiac death (DCD). Retrospective review of pediatric liver transplant (PLT) using DCD grafts. Patients were divided into either FLG or RLG recipients. Pre-transplant recipient parameters, donor parameters, operative parameters, post-transplant recipient parameters, and outcomes were compared. Overall, 14 PLTs from DCD donors between 2005 and 2018 were identified; 9 FLG and 5 RLG. All donors were Maastricht category III. Cold ischemia time was significantly longer in RLG (8.2h vs. 6.2 h; p= .038). Recipients of FLG were significantly older (180months vs. 7 months; p= .012) and waited significantly longer (168 days vs. 22 days; p= .012). Recipients of RLG tended to be sicker in the immediate pre-transplant period and this was reflected by the need for respiratory or renal support. There was no significant difference between groups regarding long-term complications. Three patients in each group survived more than 5 year post-transplant. One child was re-transplanted in the RLG due to portal vein thrombosis but failed to survive after re-transplant. One child from FLG also died from a non-graft-related cause. Selected DCD grafts are an untapped source to widen the donor pool, especially for sick recipients. In absence of agreed criteria, graft and recipient selection for DCD grafts should be undertaken with caution.

411.6: Inferior Long-term Outcomes of Simultaneous Liver-Kidney Transplantation Using Donation After Cardiac Deaths Donors in the United Network for Organ Sharing Database

Background: Outcomes of simultaneous liver-kidney transplantation (SLKT) in donation after cardiac death (DCD) have improved over the years, but data are limited. Aim of this study was to assess the long-term outcomes of SLKT from DCD organs and then compare them to donation after brain death (DBD) organs. Methods: We analyzed data from the United Network for Organ Sharing (UNOS) from 2002 to 2021. Adult SLKT were included, other multi-organ and re-transplants were excluded from the analysis. Propensity score matching was performed to assess the outcomes between two groups. P<0.05 was considered as significant. Results: In the United States, 8733 SLKT were performed during the study period (499 SLKT from DCD and 8234 from DBD). Recipients of DCD organs, when compared to recipients of DBD organs, were older (median age 59 vs 58 years, P=0.005), had lower prevalence of dialysis (62 vs 68%, P=0.003), lower Model for End-Stage Liver Disease (MELD) score (24 vs 29, P<0.001) and longer wait-time (89 vs 68 days, P=0.009). Donors of DCD organs were younger (median age 33 vs 35 years, P<0.001), had shorter cold ischemia time in liver (5.8 vs 6.0 hours, P<0.001) and in kidney (9.5 vs 10.5 hours, P<0.001), and had similar kidney donor profile index (31 vs 30 %, P=0.18) compared to DBD donor. The most common primary diagnosis for both recipient groups was alcohol-related liver disease, while non-alcoholic steatohepatitis was more common in DCD group (28 vs 21%). Long-term outcomes including five-year overall survival and liver graft survivals were inferior in DCD recipients (71.4 vs 74.8%, P=0.11; 74.0 vs 67.1%, P=0.0011). After propensity score matching, five-year overall survival and liver graft survivals were inferior (71.4 vs 76.4%, P=0.031; 67.1 vs 76.0%, P<0.001). Multivariable cox-regression analysis in the matched-cohort showed that DCD was an independent risk factor of mortality (hazard ratio {HR}- 1.33; 95% Confidence interval{CI}, 1.04-1.68; P=0.021) and liver graft failure (HR- 1.54; 95% CI, 1.24-1.92; P<0.001). For kidney allograft outcomes in matched-cohort, delayed graft function was higher in DCD (36 vs 20%, P<0.001) and five-year kidney graft outcome was inferior in DCD (67.3 vs 74.7%, P=0.0034). The most common listed causes of five-year mortality were infection (21.4%) and multi-organ failure (20.8%) and there were no differences between two groups. Other factors associated with mortality were recipient older age (HR 1.03; 95%CI 1.02-1.04, P<0.001), male recipient (HR 1.32; 95%CI 1.06-1.64, P=0.014), and donor older age (HR 1.01; 95%CI 1.00-1.02, P=0.024). Conclusion: Recipients of SLKT from DCD donors had inferior long-term post-transplant outcomes with decrease in overall survival and allograft survival. Careful identification of risk factors associated with worse outcomes is required to improve utilization of DCD donors for SLKT.

344.7: Early Post-operative Thrombotic Microangiopathy in Deceased Donor Kidney Transplant: Case Series

Background: Transplant associated thrombotic microangiopathy (TA-TMA) is well recognized as a serious complication of renal transplantation. TA-TMA is characterized by injury of arterioles and capillaries and encompasses syndromes of thrombocytopenia, microangiopathic hemolytic anemia(MAHA) and variable degrees of kidney graft dysfunction. TA-TMA can be classified into recurrent TMA (from underlying complement mutations) and de novo TMA. The incidence of de novo TMA ranges from 3-14%. Causes of de novo TMA include immunosuppressive drugs (tacrolimus, mTOR inhibitors, valgancyclovir), ischemia reperfusion injury, viral infections (CMV, Parvovirus B19, HIV, HHV-6) and antibody-mediated rejection. We have found that many of these cases also have very low levels of ADAMTS13 but do not meeting clinical criteria for TTP. If the latter is secondary to endothelial damage vs consumption process is still unknown. Objective: The purpose of this study was to identify if any specific risk factors or variables are associated with TA-TMA in the setting of deceased donor kidney transplantation (DDKT). Methods: We retrospectively collected data on 11 patients who were diagnosed with TA-TMA in the immediate post operative period (defined as less than 2 weeks from transplant date) since January, 2017. We analyzed donor characteristics including age, type of deceased donor, last known platelet count, biopsy features, pump parameters, cold ischemia time (CIT), warm ischemia time (WIT), reperfusion injury (RI) described at transplant surgery. Recipient variables included baseline platelet count on admission, the post-op day of diagnosis and at resolution (defined as platelet count > 100K and no need for additional transfusion), the use of thymoglobulin, ADAMS13 activity, changes in maintenance immunosuppression, evidence of post op bleeding, delayed graft function (DGF) and its recovery, and renal function at 1 and 3 months post transplant (Table). Results: 72% of the kidneys were from donation after cardiac death donors (DCD). The mean arterial pressure on the perfusion pump was 39 ± 7 mmHg and the flow was 148 ± 35 ml/sec. 81 % of the donor biopsies showed mild ATN, 72% had evidence of atherosclerosis and 54% of fibrosis and only one showed fibrin thrombi in the glomerulus. The mean CIT and WIT were 1913 ± 423 and 27 ± 32 min, respectively. The mean donor platelet count and baseline recipient’s platelet count were 209 ± 210 and 166 ± 71 x 10(3)/mcl, respectively. The TA-TMA event occurred on post op day 3± 1.3 with a mean platelet count of 45 ± 19 x 10(3)/mcl. ADAMTS 13 level was <10% in 54% of the cases and LDH level 2880 ± 55 U/L. 3 patients received FFP infusions, 5 received plasmapheresis and 3 received conservative treatment. The microangiopathic hemolytic anemia recovered in 10 ± 2.4 days to a platelet count of 130 ± 67 x 10(3)/mcl. There were 6 cases of post op bleeding (55%) with 4 requiring surgical intervention and 4 cases of RI (36%). Of the 8 patients that sustained DGF, 6 recovered at one month, one recovered at 3 months post transplant (having history of low C3 and late biopsy proven TMA) and one died. The mean SCr and eGFR at 1 and 3 months were 2± 1.1, 51 ± 34 and 1 ± 0.5 mg/dl and 66± 30 ml/min, respectively.There were no statistical differences on the above parameters when the patients were grouped by the presence of post operatory bleeding. However, when we added the reperfusion injury factor, we found a lower ADAMTS 13 levels of 17 ±7 UI/dl in the non bleeding group who sustained RI (60%) vs 21± 37 UI/dl in the bleeding group who had only one patient with RI (17%) (p=0.24). Conclusions: TA-TMA in the immediate postoperative period can be difficult to diagnose and treat. Our findings demonstrated that 55% of the cases were associated with post operatory bleeding leading to the reduction of ADAMTS 13 levels, most likely by platelet consumption. 36% were related to reperfusion injury where the consumption of ADAMTS 13 could be explained by direct endothelial damage. None of the patients needed other than conservative therapy. This data needs to be correlated in a larger cohort. In this context we are planning to prospectively study ADAMTS 13 activity in the immediate post kidney transplant period.

P11.07: BMSCs Combined With Normothermic Machine Perfusion Resuscitate Aged Donor Liver With Long Warm Ischemia Time in Rats

Background: Both aged and donation after cardiac death (DCD) donor liver, considered as marginal organs, were used for transplantation due to huge organ shortage in the world. Organs combined with both danger factors would impair the donor liver viability. Using normothermic machine perfusion (NMP), we investigated the possibility of mesenchymal stem cells (MSCs) to revive the aged DCD donor liver in a rat model. Methods: The SD rats used for NMP were all over 14 months of age. BMSCs were isolated from the bone marrow of SD rats. Rats were anesthetized and cardiac arrest was induced by compression of the heart for 30 minutes as warm ischemia prior to donor liver harvesting. The liver was connected to a rat liver perfusion machine for NMP with or without 10^6 BMSCs infusion. Results: The weight of the aged liver in the experimental and control groups was 23.03 ± 0.25 g and 21.40 ± 0.87 g. the donor liver appeared to multiple bruised foci in both prior- and post- perfusion, while liver with BMSCs perfusion had fewer bruised foci (Figure 1A, B). The pH was maintained between 7.35 and 7.45 in both groups during perfusion. Lactate in the BMSCs group decreased after 1 hour during perfusion and fell below 1 gradually within 3 hours, while in the control group it decreased more slowly and remained around 4 even after 4 hours of perfusion (Figure 1C). Pathological appearance showed that the pathological Suzuki‘s sores of liver in the control group were higher than MSCs group, with bruised liver sinusoids, apoptosis and focal necrosis of hepatocytes. In contrast, pathological change in the liver of the BMSC group showed significant improvement with no obvious necrosis and structural integrity of the liver lobules (Figure 1D). The climbing rate and peak value of AST and ALT in the BMSCs group were lower than that in the control group, indicating that BMSCs protected liver from damage during perfusion (Figure 1E, 1F). Conclusion: Our results demonstrate that the use of MSCs during normothermic machine perfusion is a feasible strategy to resuscitate the aged DCD donor liver.National Natural Science Foundation of China (81401324 and 81770410).

Heart Transplant Outcomes with Donation After Cardiac Death: UNOS Registry Analysis

<h3>Purpose</h3> Limitations in organ donation have led to approaches to expand the existing donor pool. Donation after cardiac death (DCD) has continued to increase after efforts led by the United Kingdom and Australia. We sought to describe the United States experience. <h3>Methods</h3> 5153 heart transplant (HT) recipients were identified in the UNOS Registry between 1/2019 and 6/2021, of which 229 were DCD recipients. HT recipients were grouped by DCD status or donation after brain death (DBD). Comparisons between groups were assessed using standard statistical methods, survival analysis was censored at 12-months via the Kaplan-Meier method. Multivariate Cox proportional hazard regression analysis (adjusted for age, sex, diabetes, race, ischemic time, dialysis, life support, waiting time & HLA mismatch) were performed. <h3>Results</h3> Recipients of DCD donors were of lower UNOS status (p<0.001), increased VAD use (p=0.01), and less dialysis (p=0.011). Additionally, DCD donor recipients had longer wait times (46.0 vs 30.0d, p=0.007), longer ischemic times (p<0.001) but younger donors (29.8 vs 23.4y, p<0.001). There was no difference in 1-month or 1-year survival by donor type (p=0.720). Unadjusted analysis demonstrated HR 0.91 (0.52-1.57) and following adjustment HR 0.88 (0.48-1.61). <h3>Conclusion</h3> Short-term survival of DCD donors is similar to DBD donors in this UNOS Registry analysis. DCD donor use has potential to expand the donor pool. Further study is warranted to assess longer term outcomes as well as best strategies for donation.

Lung Transplant from a DCD Donor with a Previous Symptomatic COVID Infection

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide pandemic affecting more than 172 million confirmed cases. The likelihood of historic donor infection is increasing. Here we report a lung transplantation of a previously SARS-CoV-2 positive organ donor.Case ReportA 49-year-old female who underwent left single lung transplantation for interstitial lung disease. The lung was obtained from a donation after cardiac death (DCD) using abdominal rerperfusion of a 23 years old female donor died of intracranial bleeding with history of covid infection 8 month prior to lung donation. According to the donor records, the symptoms were mild, and required no hospital admission. She had ongoing loss of taste and smell till time of donation. There were no respiratory symptoms. At time of retrieval, chest x ray was normal and blood gases were normal, however, bronchoscopy revealed severe inflammation of the right-side mucosa so the decision was to proceed with the left lung only as it had normal blood gases, good recruitment and no consolidation as well as non inflamed bronchial mucosa. patient had single off pump left lung transplant through left anterior thoracotomy approach. After the surgery, patient was extubated on day 1 in ICU, discharged from ICU on day 3 and discharged from the hospital after 27 days. There was no evidence for primary graft dysfunction or acute rejection. After 6 month of the surgery, FVC is 2.26 L (78.2% predicted) and FEV1 is 1.9L (70.2% predicted).SummaryThis case showed that it is possible to proceed with lung transplant from a donors who had previous mild covid infection. As DCD donation might limit preoperative invasive investigations such as bronchoscopies careful examination and proper radiological and functional assessment for the donor lung after donation including EVLP needs to be considered.

Histological evaluation of ischemic alterations in donors after cardiac death: A useful tool to predict post-transplant renal function.

Kidneys retrieved from donors after cardiac death (DCD) pose significant challenges from a clinical and technical point of view, undergoing a variable degree of ischemia-reperfusion injury. At present, the utilization of kidneys is assessed according to the Karpinski score, which does not take into account the ischemic insult and does not predict the functional recovery of the organ once transplanted. Therefore, the correlation between biopsy results and post-transplant graft function is still debated. In this study we examined kidney biopsies from DCD donors; we calculated the Karpinski score and subsequently identified and quantified the ischemic lesions in the glomerular, interstitial, and tubular compartments. These same lesions were quantified in kidney biopsies from donors after brain death (DBD) in a case-control analysis. The collected data were correlated with the clinical data of the donors and the post-transplant follow-up. Proximal tubule alterations are crucial in ischemia-reperfusion damage, showing precise histological alterations, which are more frequent in DCD than in DBD donors and are statistically correlated with functional recovery of the organ. Quantification of ischemic tubular lesions in biopsies of kidneys from DCD donors is a useful tool for predicting post-transplant renal function and a valid parameter for assessing the quality of the graft.

Outcome of Liver Transplants Using Donors After Cardiac Death With Normothermic Regional Perfusion

The incorporation of normothermic regional perfusion (NRP) to donors after cardiac death (DCD) allows the recovery of liver grafts without the deleterious effects on graft survival the super-rapid technique may cause. The aim of the present report is to determine if the use of NRP in Maastricht type III DCD donors achieves short- and medium-term results comparable to donors after brain death (DBD). This is an observational cohort study including 117 liver transplants executed between November 2016 and April 2021, divided into NRP (n=39) and DBD (n=78). Donors were younger in the NRP group (NRP 52 vs DBD 59.4 years; P < .005). Liver recipients in each study group were of similar age and severity of liver disease, although the predominant transplant indication in the NRP group was hepatocellular carcinoma. No differences in ischemia times were found. The incidence of early allograft disfunction and primary nonfunction was balanced between NRP and DBD. Eight patients required retransplant, all of them in the DBD group. No differences were found in biliary complications (NRP 12% vs DBD 5%; P=.104). Ischemic cholangiopathy affected a single DBD patient. Graft survival's Kaplan Meier curve shows a better outcome in the NRP group, although the difference did not reach significance (P=.075). The incorporation of perfusion machines, and specifically the NPR in situ, converts suboptimal liver grafts such as DCD into organs comparable to DBDs.

Results from an International Survey of Donor and Recipient Eligibility for Solid Organ Pancreas Transplantation.

BackgroundCurrent solid organ pancreas transplantation protocols have differing donor criteria for donor pancreas acceptance and recipient eligibility criteria for transplant workup. We quantified this variation and compared current Australia and New Zealand (ANZ) solid pancreas transplant eligibility criteria with current international practice.Material/MethodsA survey of donor and recipient eligibility criteria for solid pancreas transplantation was disseminated to 85 transplant units in 23 countries. Responses were grouped by regions (ANZ, North America, Eurotransplant, Europe, United Kingdom) and analyzed for significant differences between regions and for ANZ compared to all other regions.ResultsResponding UK pancreas transplant units reported the highest mean donor upper age limit (61 years old) and the highest mean donation after cardiac death donor (DCD) age limit (55 years old). All responding UK and USA units utilized DCD pancreas donors and accepted suitable type 2 diabetes (T2DM) recipients for pancreas transplantation; however, this was less common among responding European or Eurotransplant units. ANZ mean standard and DCD pancreas donor upper age limits (47 and 35 years old, respectively) were lower compared to all other regions (54 years old and 48 years old, respectively).ConclusionsPancreas donor age limits, DCD pancreas donor utilization, and transplanting T2DM recipients differ between responding pancreas transplant units. ANZ units have more conservative donor upper age limits compared to other responding units. Increased utilization of DCD pancreas donors and T2DM recipients while standardizing pancreas donor age limits might increase donor numbers and improve access to solid pancreas transplantation both locally and abroad.

Donor type and 3-month hospital readmission following kidney transplantation: results from the Netherlands organ transplant registry

BackgroundHospital readmission after transplantation is common in kidney transplant recipients (KTRs). In this study, we aim to compare the risk of 3-month hospital readmission after kidney transplantation with different donor types in the overall population and in both young (< 65 years) and elderly (≥65 years) KTRs.MethodsWe included all first-time adult KTRs from 2016 to 2018 in the Netherlands Organ Transplant Registry. Multivariable logistic regression models were used to estimate the effect while adjusting for baseline confounders.ResultsAmong 1917 KTRs, 615 (32.1%) had at least one hospital readmission. Living donor kidney transplantation (LDKT) recipients had an adjusted OR of 0.76 (95%CI, 0.61 to 0.96; p = 0.02) for hospital readmission compared to deceased donor kidney transplantation (DDKT) recipients. In the young and elderly, the adjusted ORs were 0.69 (95%CI, 0.52 to 0.90, p = 0.01) and 0.93 (95%CI, 0.62 to 1.39, p = 0.73) and did not differ significantly from each other (p-value for interaction = 0.38). In DDKT, the risk of hospital readmission is similar between recipients with donation after cardiac death (DCD) or brain death (DBD) and the risk was similar between the young and elderly.ConclusionA lower risk of post-transplant 3-month hospital readmission was found in recipients after LDKT compared to DDKT, and this benefit of LDKT might be less dominant in elderly patients. In DDKT, having either DCD or DBD donors is not associated with post-transplant 3-month hospital readmission, regardless of age. Tailored patient management is needed for recipients with DDKT and elderly KTRs.