Donation After Circulatory Death Recipients Research Articles

Hemodynamic and Clinical Performance of Hearts Donated After Circulatory Death

BackgroundDonor organ demand continues to outpace supply in heart transplantation. Utilization of donation after circulatory death (DCD) hearts could significantly increase heart donor availability for patients with advanced heart failure. ObjectivesThe purpose of this study was to describe hemodynamic and clinical profiles of DCD hearts in comparison to standard of care (SOC) hearts donated after brain death (DBD). MethodsThis single-center retrospective cohort study of consecutive heart transplant recipients analyzed right heart catheterization measurements, inotrope scores, echocardiograms, and clinical outcomes between DCD and DBD heart recipients. ResultsBetween April 2016 and February 2022, 47 DCD and 166 SOC hearts were transplanted. Median time from DCD consent to transplant was significantly shorter compared with SOC waiting list time (17 days [6-28 days] vs 70 days [23-240 days]; P < 0.001). Right heart function was significantly impaired in DCD recipients compared with SOC recipients 1 week post-transplant (higher median right atrial pressure (10 mm Hg [8-13 mm Hg] vs 7 mm Hg [5-11 mm Hg]; P < 0.001), higher right atrial pressure to pulmonary capillary wedge pressure ratio (0.64 [0.54-0.82] vs 0.57 [0.43-0.73]; P = 0.016), and lower pulmonary arterial pulsatility index (1.66 [1.27-2.50] vs 2.52 [1.63-3.82]; P < 0.001), but was similar between groups by 3 weeks post-transplant. DCD and SOC recipient mortality was similar at 30 days (DCD 0 vs SOC 2%; P = 0.29) and 1 year post-transplant (DCD 3% vs SOC 8%; P = 0.16). ConclusionsDCD heart utilization is associated with transient post-transplant right heart dysfunction and short-term clinical outcomes otherwise similar to transplantation using DBD hearts.

Post-Kidney Transplantation Results After Circulatory or Brain Death Without Pre-Mortem Heparin Administration.

BackgroundKidney donation after circulatory death (DCD) follows confirmation of death using cardiorespiratory criteria, while donation after brain death (DBD) uses neurological criteria. DBD and DCD donors are the main sources of grafts for transplantation. This retrospective cohort study from a single center in the Czech Republic aimed to compare 5-year post-transplantation outcomes after DCD and DBD transplantation without pre-mortem heparin administration.Material/MethodsA total of 227 recipients with matched donors enrolled in the transplantation program at our institution between 2015 and 2019 were analyzed. Following the application of the inclusion criteria, 99 recipients and 94 matched donors were finally included in the study.ResultsThe duration of cold ischemia (median 961 vs 1100 min, P=0.028) and the perfusion with the preservation solution (median 11 vs 22 min, P<0.001) was statistically significantly shorter in DBD than in DCD grafts. The 1-year survival rates were 97.5% (95% CI 94.1–100.0%) and 90.0% (95% CI: 77.8–100.0%) for DBD and DCD recipients, respectively. The 3-year survival rates were 91.9 (95% CI: 86.0–98.4) and 90.0 (95% CI: 77.8–100.0) for the DBD and DCD groups, respectively. The overall difference in survival between the 2 groups of patients was not statistically significant (P=0.750) nor was disease-free survival (P=0.370).ConclusionsThis retrospective study from a single center showed similar 5-year results after kidney transplantation for DCD and DBD donors without pre-mortem heparin administration, including the time to graft failure and patient survival.

Results of Heart Transplants from Donation After Circulatory Death (DCD) Donors Using Thoraco-Abdominal Normothermic Regional Perfusion (TA-NRP) Compared to Donation After Brain Death (DBD)

<h3>Purpose</h3> In the U.S., heart transplantation from donation after circulatory death (DCD) is increasing. We present our institutional experience of DCD transplantation by using a thoracoabdominal-normothermic regional perfusion (TA-NRP) protocol and compare the results to a cohort concomitantly transplanted, from standard brain death (DBD) donation. <h3>Methods</h3> For TA-NRP protocol, suitable local DCD donors were transferred to our institution and co-located with the recipient in proximate operating rooms. Standard DCD procurement involved resuscitation of the donor on cardiopulmonary bypass after declaration of death and assessment for suitability by echocardiogram and hemodynamic data. Heart transplant from DBD was performed per standard protocol. Immunosuppression and management followed the same standardized protocol for all recipients. <h3>Results</h3> Between January 2020 and October 2021, we performed 10 DCD transplantations with TA-NRP protocol (7 isolated heart, 2 heart-lung and 1 heart-kidney). The median age was 54 years (44-72), and 70% were male. One heart-lung transplant recipient required VA ECMO post-op, for 3 days. During the same period, 70 patients received heart transplant from a DBD donor (71.4% isolated heart, 7.1% heart-lung, 21.4% heart-kidney). The median age was 56 years (24-77) - p=0.916, 84.% were male p=0.27. At mean follow-up of 397.6 days (DCD recipients) and 305.9 days (DBD recipients), there were no significant differences in acute cellular, antibody mediated rejection, cardiac allograft vasculopathy, heart graft function, and survival. Compared to DBD recipients, DCD recipients received transplant at lower listed statuses. <h3>Conclusion</h3> Short-term results suggest that transplant outcomes from DCD TA-NRP are comparable to recipients from DBD. Expanding heart transplantation by using DCD is a viable option for lower-status listed patients and wide adoption should be considered.

Adult Lung Transplantation from Donation After Circulatory Death Donors: Safety and Outcomes Utilizing the UNOS / OPTN Registry

<h3>Purpose</h3> Donation after circulatory death (DCD) has been described in abdominal transplantation but has not been thoroughly evaluated in lung transplantation. The aim of this retrospective study was to describe and compare DCD utilization with donation after brain death (DBD). <h3>Methods</h3> The United Network for Organ Sharing (UNOS) database was reviewed for all adult patients who underwent lung transplant between 2016 and 2020. Baseline features and post-transplant outcomes were reviewed using descriptive and survival analyses by the Kaplan-Meier and Cox regression method. <h3>Results</h3> A total of 11,837 isolated lung transplant recipients met criteria for analysis. DCD utilization increased over time, from 92/2198 (14.7%) in 2016 to 180/2376 (28.8%) recipients in 2020 (p<0.001 for trend). DCD patients were more likely double lung recipients (79.9 vs 74.6%), had longer ischemia times (7.6 vs. 5.5 h), and were more commonly intubated (42.8 vs. 29.9%) and required extracorporeal support (12.5 vs 7.2%) up to 72 h following surgery (Table 1). Unadjusted overall survival was worse for DCD vs DBD patients (log rank, p<0.001). When stratified by transplant type, there was no survival difference between DCD and DBD single lung recipients (log rank, p=0.322); however, survival among double lung recipients was worse for DCD vs DBD patients (log rank, p<0.001). After adjustment for statistically significant covariates (Table 1), DCD status was not associated with mortality for double lung recipients (HR: 1.189, 95% CI [0.985 - 1.435]; p=0.071). Ischemia time (HR: 1.029, 95% CI [1.007 - 1.052]; p=0.010) and extracorporeal support (HR: 2.862, 95% CI [2.512 - 3.260]; p<0.001) after transplant were more common in DCD patients and strongly associated with mortality up to 5 years. <h3>Conclusion</h3> DCD status was associated with worse survival in double lung transplant recipients, which may be attributed to longer ischemia times. Additional efforts will be required to characterize and mitigate these effects.

Heart Transplantation from Donation After Circulatory Death Donors: An Update on the Australian Experience

<h3>Purpose</h3> With an expanding end-stage heart failure population the demand for donor hearts is increasing. Donation after circulatory death (DCD) is a pathway that could help address this; we explore the impact of DCD over the last 8-years on our unit and compare our early vs contemporary outcomes. <h3>Methods</h3> All DCD heart transplants at our unit were included. Inclusion criteria for DCD donors are: normal transthoracic echo, age <55yrs & nil previous cardiac history. DCD heart retrievals are subject to varying functional (when systolic blood pressure drops <90mmHg) and asystolic warm ischemic times (aWIT) prior to administration of cardioplegia - this warrants an assessment of viability through visual inspection and monitoring of lactate levels. Donor hearts are cannulated onto an ex-vivo normothermic machine perfusion device where 1.2-1.5L of donor blood is circulated in a Langendorff fashion. <h3>Results</h3> Since 2014 we have performed 69 DCD heart transplants. Since 2020, DCD donors account for 32% of our heart transplant activity (32/100). Overall 1yr & 5yr survival for DCD vs BD donor heart transplant recipients was not significantly different (p=0.27). In the early experience, 12/34 patients (35.3%) required immediate post-operative ECMO or mechanical support. Recent recipients have a significantly lower rate with 3/35 (8.57%) requiring ECMO/mechanical support post-transplant (p=0.009). Mean DCD donor & recipient age was 32.6yrs(+/-10.5yrs) & 53.6yrs(+/-12.7yrs) respectively. Mean donor aWIT was 12.3mins (+/-2.8mins). Recipients of donors with an aWIT >15mins had significantly higher post-transplant ECMO/mechanical support requirement compared to those with an aWIT <=15mins (66.17% vs 17.46%, p=0.0177, OR 9.455). Median hospital length of stay was 17.5days (11-27.5days). <h3>Conclusion</h3> DCD donors can contribute to heart transplantation activity with survival comparable to BD pathways. Donor hearts subject to an aWIT >15mins are more likely to require post-operative ECMO/mechanical support.

Early Allograft Dysfunction After Liver Transplantation With Donation After Circulatory Death and Brain Death Grafts: Does the Donor Type Matter?

Background.Early allograft dysfunction (EAD) after liver transplantation has been associated with long-term reduced graft and patient survival.Methods.In this single-center cohort study, we aimed to compare incidence, risk factors, and outcomes in liver transplant recipients who developed EAD. Patients who received donation after circulatory death (DCD) or donation after brain death (DBD) grafts between January 2007 and December 2017 were included. EAD was defined as bilirubin of ≥10 mg/dL (171 μmol/L) or an international normalized ratio of ≥1.6 on postoperative day 7 or transaminases >2000 U\\L in the first-week posttransplantation as previously described.Results.In our cohort of 1068 patients, incidence of EAD was 44%. EAD occurred more frequently in the DCD versus DBD group (71% versus 41%, P < 0.01). Overall, recipients who developed EAD showed a significantly lower graft and patient survival at 1, 3, and 5 y after transplantation (all P < 0.05). This was also the case for recipients of DBD grafts. However, for recipients of DCD grafts, patient and graft survival were not affected by the presence of EAD. For recipients of DBD grafts, donor age, body mass index (BMI) and gender, recipient BMI and model for end-stage liver disease score and warm and cold ischemia time were associated with EAD. For DCD recipients, donor BMI and cold ischemia time were associated with EAD.Conclusions.In our cohort study, EAD resulted in reduced long-term patient and graft survival only for DBD recipients but not for DCD recipients. Predictive markers for EAD were dependent on the donor type.

Clinical and Functional Outcomes after Lung Transplantation with Grafts from Donation after Circulatory (DCD) Donors. Preliminary Results of a Clinical Trial

<h3>Purpose</h3> We present the results of a clinical trial (NCT02061462) comparing outcomes after lung transplantation (LT) of subjects receiving lungs from donation after brain death (DBD) donors with that of subjects receiving lungs from donation after circulatory death (DCD) donors, procured using our original open lung strategy. Briefly, our protocol consists of a non-rapid normothermic open-lung procurement using recruitment manoeuvres, protective ventilation and CPAP without topical cooling. <h3>Methods</h3> We evaluated patients undergoing bilateral LT from 11/2014 to 07/2019; exclusion criteria: recipients ≤14 years, re-LT, donors ≥65 years, DCD category I and IV. Variables were prospectively recorded as well as respiratory functional parameters in the first year. <h3>Results</h3> We performed 143 LT; 22 cases were excluded, 121 were enrolled: 11 recipients received lungs from DCD donors (5 and 6 from DCD category II and III, respectively). The two groups had similar features. Most of the subjects had cystic fibrosis (72,7% and 61,9% of DCD and DBD, respectively). DCD donors' BMI was significantly higher (p=0.022); 15,5% of DBD grafts underwent machine perfusion. Duration of postoperative mechanical ventilation was higher in the DCD group (DCD vs DBD=2 vs 1 day, p=0.011). Incidence of grade 3 primary graft dysfunction was 27,3% in the DCD group and 18,2% in the DBD group (p=0.742). Cold ischemia and preservation times were significantly higher in the DCD group (p<0.001). Airway complications occurred in 18,2% and 6,4% in DCD and DBD recipients, respectively (Table 1). Mean FEV1 was significantly higher in the DBD group at 6 months (83,5% vs 78,5%) but not at 1 year (86,0% vs 81,7%). FVC and Tiffenau did not significantly differ. <h3>Conclusion</h3> Regardless of the small study population, our results are encouraging. Our data show the feasibility of LT from DCD donors using our original protocol, with adequate grafts function and survival.

Controlled DCD Liver Transplantation Is Not Associated With Increased Hyperfibrinolysis and Blood Loss After Graft Reperfusion.

The specific effect of donation after circulatory death (DCD) liver grafts on fibrinolysis, blood loss, and transfusion requirements after graft reperfusion is not well known. The aim of this study was to determine whether transplantation of controlled DCD livers is associated with an elevated risk of hyperfibrinolysis, increased blood loss, and higher transfusion requirements upon graft reperfusion, compared with livers donated after brain death (DBD). A retrospective single-center analysis of all adult recipients of primary liver transplantation between 2000 and 2019 was performed (total cohort n = 628). Propensity score matching was used to balance baseline characteristics for DCD and DBD liver recipients (propensity score matching cohort n = 218). Intraoperative and postoperative hemostatic variables between DCD and DBD liver recipients were subsequently compared. Additionally, in vitro plasma analyses were performed to compare the intraoperative fibrinolytic state upon reperfusion. No significant differences in median (interquartile range) postreperfusion blood loss (1.2 L [0.5-2.2] versus 1.3 L [0.6-2.2]; P = 0.62), red blood cell transfusion (2 units [0-4] versus 1.1 units [0-3]; P = 0.21), or fresh frozen plasma transfusion requirements (0 unit [0-2.2] versus 0 unit [0-0.9]; P = 0.11) were seen in DCD compared with DBD recipients, respectively. Furthermore, plasma fibrinolytic potential was similar in both groups. Transplantation of controlled DCD liver grafts does not result in higher intraoperative blood loss or more transfusion requirements, compared with DBD liver transplantation. In accordance with this, no evidence for increased hyperfibrinolysis upon reperfusion in DCD compared with DBD liver grafts was found.

Utilization of extracorporeal membrane oxygenation in DCD and DBD lung transplants: a 2-year single-center experience.

Donation after circulatory death (DCD) has the potential to expand the lung donor pool. We aimed to assess whether DCD affected the need for perioperative extracorporeal membrane oxygenation (ECMO) and perioperative outcomes in lung transplantation (LTx) as compared to donation after brain death (DBD). All consecutive LTxs performed between April 2017 and March 2019 at our tertiary center were analyzed. Donor and recipient preoperative characteristics, utilization of ECMO, and perioperative clinical outcomes were compared between DCD and DBD LTx. Multivariate models (frequentist and Bayes) were fitted to evaluate an independent effect of DCD on the intra- and postoperative need for ECMO. Out of 105 enrolled patients, 25 (23.8%) were DCD LTx. Donors' and preoperative recipients' characteristics were comparable between the groups. Intraoperatively, mechanical circulatory support (MCS) was more common in DCD LTx (56.0% vs. 36.2%), but the adjusted difference was minor (RR=1.16, 95% CI 0.64-2.12; P=0.613). MCS duration, and first and second lung ischemia time were longer in the DCD group. Postoperatively, DCD recipients more commonly required ECMO (32.0% vs. 7.5%) and the difference remained considerable after adjustment for the pre- and intraoperative covariates: RR=4.11 (95% CI 0.95-17.7), P=0.058, Bayes RR=4.15 (95% CrI 1.28-13.0). Sensitivity analyses (two DCD-DBD matching procedures) supported a higher risk of postoperative ECMO need in DCD patients. Incidence of delayed chest closure, postoperative chest drainage, and renal replacement therapy was higher in the DCD group. Early postoperative outcomes after DCD LTx appeared generally comparable to those after DBD LTx. DCD was associated with a higher need for postoperative ECMO which could influence clinical outcomes. However, as the DCD group had a significantly higher use of EVLP with more common ECMO preoperatively, this might have contributed to worse outcomes in the DCD group.

Hypothermic Oxygenated Liver Perfusion (HOPE) Prevents Tumor Recurrence in Liver Transplantation From Donation After Circulatory Death.

The aim of this study was to investigate tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC), with and without hypothermic oxygenated liver perfusion (HOPE) before transplantation. We analyzed all liver recipients with HCC, transplanted between January 2012 and September 2019 with donation after circulatory death (DCD) livers after previous end-ischemic HOPE-treatment (n = 70, Center A). Tumor parameters and key confounders were compared to consecutive recipients with HCC, transplanted during the same observation period with an unperfused DBD liver (n = 70). In a next step, we analyzed unperfused DCD (n = 70) and DBD liver recipients (n = 70), transplanted for HCC at an external center (Center B). Tumor parameters were not significantly different between HOPE-treated DCD and unperfused DBD liver recipients at Center A. One-third of patients were outside established tumor thresholds, for example, Milan criteria, in both groups. Despite no difference in tumor load, we found a 4-fold higher tumor recurrence rate in unperfused DBD livers (25.7%, 18/70), compared to only 5.7% (n = 4/70) recipients with tumor recurrence in the HOPE-treated DCD cohort (P = 0.002) in Center A. The tumor recurrence rate was also twice higher in unperfused DCD and DBD recipients at the external Center B, despite significant less cases outside Milan. HOPE-treatment of DCD livers resulted therefore in a 5-year tumor-free survival of 92% in HCC recipients, compared to 73%, 82.7%, and 81.2% in patients receiving unperfused DBD or DCD livers, from both centers. We suggest that a simple machine liver perfusion approach appears advantageous to protect from HCC recurrence after liver transplantation, despite extended tumor criteria.

PROPENSITY SCORE MATCHED RISK OF BILIARY COMPLICATIONS AFTER LIVER TRANSPLANT AND OUTCOME BY DONOR TYPE

Background: Donation after circulatory death (DCD), donation after brain death (DBD), and living donor (LD) liver transplantation (LT) are three types of donors used in patients with end-stage liver diseases. Each type has unique benefits, risks, and potential complications. In this study, we assess the risk of biliary complications, and their effect on long-term outcome. Methods: We collected data on all consecutive DCD, DBD and LD-LT recipients between 1989 and 2019 from a single center, and used propensity score matching to identify three groups. Patient survival, graft survival, and biliary complications (bile leak, anastomotic (AS) and non-anastomotic strictures (NAS)) were analyzed and compared between groups. Adjusted p-values were calculated using multivariate Cox regression models. Results: We identified 141 DCDs, 3,226 DBD, and 386 LD-LT in our cohort, with significantly different recipient age, gender, etiology of liver disease, Na-Model for End-Stage Liver Disease (MELD), incidence of hepatocellular carcinoma (HCC), and donor age, gender, and cold ischemic time. Propensity score matching allowed correction for all differences except MELD, presence of HCC, and etiology of liver disease. This produced three groups of 138 recipients each. Adjustment for MELD, HCC, and etiology of liver disease was then performed using Cox models. Eighteen LT recipients (4.3%) had arterial complications (thrombosis and stenosis; no difference between groups). Bile leak was identified in 10.1% of DCD-LTs, versus 7.2% of DBD-LTs, and 36.2% of LD-LTs (p-values=0.240 and <0.001, respectively). Anastomotic biliary stricture developed in 28.3% DCD-LTs, versus 18.1% of DBD-LTs, and 43.5% of LD-LTs (p-values=0.038 and 0.006, respectively). Non-anastomotic biliary stricture was present in 15.2% of DCD-LT s, versus 1.4% of DBDs-LT, and 4.3% of LD-LTs (p-values=0.004 and 0.005, respectively). Eighteen patients (4.3%) were retransplanted and there was no significant difference in retransplant rate between groups. LD-LTs free of any biliary complications had the best patient survival whereas DCD-LTs with ≥1 biliary complication (presence of a bile leak and/or AS and/or NAS) had the worst survival (Figure). Among the 21 DCD-LT patients with non-anastomotic strictures, six died, two were retransplanted, three remain stent dependent, and ten were ultimately stent-free. Conclusion: DCD and LD-LT recipients had significantly higher rates of biliary complications. Biliary complications in DCD-LTs had the most significant impact on survival, although two thirds of the recipients with ischemic cholangiopathy could ultimately achieve a favorable outcome.

Immunosuppression in Donation After Circulatory Death Liver Transplantation: Can Induction Modify Graft Survival?

Recipients of donation after circulatory death (DCD) LTs historically have an increased risk of graft failure. Antibody induction (AI) with antithymocyte globulin (ATG) or anti-interleukin 2 receptor (anti-IL2R) immunotherapy may decrease the incidence of graft failure by mitigating ischemia/reperfusion injury. A retrospective review of the United Network for Organ Sharing (UNOS) database for LTs between 2002 and 2015 was conducted to determine whether ATG or anti-IL2R AI was associated with graft survival in DCD. A secondary endpoint was postoperative renal function as measured by estimated glomerular filtration rate at 6 and 12 months. Among DCD recipients, ATG (hazard ratio [HR]=0.71; P=0.03), but not anti-IL2R (HR=0.82; P=0.10), was associated with a decrease in graft failure at 3 years when compared with recipients without AI. ATG (HR=0.90; P=0.02) and anti-IL2R (HR=0.94; P=0.03) were associated with a decreased risk of graft failure in donation after brain death (DBD) liver recipients at 3 years compared with no AI. When induction regimens were compared between DCD and DBD, only ATG (HR=1.19; P=0.19), and not anti-IL2R (HR=1.49; P<0.01) or no AI (HR=1.77; P<0.01), was associated with similar survival between DCD and DBD. In conclusion, AI therapy with ATG was associated with improved longterm liver allograft survival in DCD compared with no AI. ATG was associated with equivalent graft survival between DCD and DBD, suggesting a beneficial role of immune cell depletion in DCD outcomes.

The Comparable Efficacy of Lung Donation After Circulatory Death and Brain Death: A Systematic Review and Meta-analysis.

Lung transplantations (LTx) have become an effective lifesaving treatment for patients with end-stage lung diseases. While the shortage of lung donor pool and severe posttransplantation complications exaggerate the obstacle of LTx. This meta-analysis aimed to evaluate the efficacy of donation after circulatory death (DCD) in LTx for patients with end-stage lung diseases. PubMed, EmBase, and Web of Science were systematically searched for all relevant studies comparing the efficacy of DCD and conventional donation after brain death (DBD). The relative risk (RR) value as well as the weighted mean difference with a 95% confidence interval (CI) were pooled for dichotomous and continuous outcomes, respectively. The heterogeneity across the included studies was also assessed carefully. Overall, 17 studies with 995 DCD recipients and 38 579 DBD recipients were included. The pooled analysis showed comparable 1-year overall survival between the 2 cohorts (RR 0.89, 95% CI, 0.74-1.07, P = 0.536, I = 0%). The airway anastomotic complications rate in DCD cohort was higher than that in DBD cohorts (RR 2.00; 95% CI, 1.29-3.11, P = 0.002, I = 0%). There was no significant difference between DCD and DBD regarding the occurrence of primary graft dysfunction grade 2/3, bronchiolitis obliterans syndrome, acute transplantation rejection, and length of stay. The stability of the included studies was strong. Evidence of this meta-analysis indicated that the use of lungs from DCD donors could effectively and safely expand the donor pool and therefore alleviate the crisis of organ shortage.

Urinary TIMP-2 Predicts the Presence and Duration of Delayed Graft Function in Donation After Circulatory Death Kidney Transplant Recipients.

Urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP7) have been validated as biomarkers for acute kidney injury. We investigated the performance of both markers in predicting the occurrence and duration of functionally defined delayed graft function (fDGF) in donation after circulatory death (DCD) kidney transplant recipients. Urine samples of 74 DCD recipients were analyzed. TIMP-2 and IGFBP7 were measured with ELISA on postoperative days 1 to 7, day 10, week 6, and month 6, and values were corrected for osmolality (mOsm). Immunosuppression consisted of anti-CD25 antibody induction and triple maintenance therapy (steroids, mycophenolate mofetil, and calcineurin inhibitor). Statistical analysis included receiver operating characteristic curves and multivariate logistic regression. Fifty-one (69%) renal transplant recipients had fDGF, of which 14 experienced prolonged fDGF (≥21 days). TIMP-2/mOsm on day-1 and day-10 adequately identified patients with fDGF (area under the curve [AUC], 0.91) and prolonged fDGF (AUC, 0.80), respectively, whereas IGFBP7/mOsm did not (AUC, 0.63 and 0.60). Multivariate analysis on day 1 identified 24-hour urinary creatinine excretion and TIMP-2/mOsm as significant predictors of fDGF (AUC, 0.90, 95% confidence interval, 0.80-0.98). The best predictors of prolonged fDGF on day 10 were 24-hour urinary creatinine excretion, TIMP-2/mOsm, and total warm ischemia time with an AUC of 0.85 (95% confidence interval, 0.72-0.95). Consecutive TIMP-2/mOsm values showed a decrease in TIMP-2/mOsm before an increase in estimated glomerular filtration rate, enabling us to monitor fDGF and predict resolution of fDGF. Urinary TIMP-2, but not IGFBP7, is a promising biomarker to predict the occurrence and duration of fDGF in DCD kidney transplant recipients.

DCD Donor Hearts Recipients Compared to DBD Donor Heart Recipients Present with Comparable Systolic Left Ventricular Function and Better Myocardial Strain at 1 Year Follow Up

Purpose Cardiac transplantation from donation after circulatory death (DCD) has been implemented at Papworth hospital since February 2015. Despite encouraging results some concerns may be raised about the impact of the warm ischemia and reperfusion injury on the myocardium status at longer follow-up. Therefore, we aimed to analyse systolic performance of the left ventricle at 1 year follow in DCD and donation after brain death (DBD) cardiac recipients, as assessed by echocardiography with myocardial deformation imaging. Methods We identified 26 DCD cardiac recipients who were transplanted from February 2015 to February 2017 and we matched them with 26 DBD cardiac recipients. Three and 2 patients from DCD and DBD group, respectively, died in the first-year post transplant. In the remaining patients we have compared the classical echocardiographic measurements as well as global longitudinal strain (GLS) and global circumferential strain (GCS) at 1-year follow-up. Results DCD and DBD patients did not present with differences in terms of classical echocardiographic parameters of left ventricular (LV) structure and systolic function. LVEDV was similar in DCD and DBD patients (102+/-37 vs. 99+/-21 ml, respectively), as well as LVESV (44+/-12 vs. 43 +/- 18 ml, respectively) and LV mass (157+/-36 vs. 169+/-44 gr). LV ejection fraction was similar in two groups (57+/- 7 vs. 58+/-8 %), as well as GLS (-15.9+/-2.3 vs. 14.8+/- 1.9%, p=0.1) and GCS (-23.7+/-5.7 vs. -20.3+/-4.1, p=0.05). In both groups 3 patients presented with left ventricular dysfunction secondary either to primary graft dysfunction or cellular rejection. When we limited analysis to the patients who presented at 1 year follow up with LVEF>=50%, DCD and DBD cardiac recipients presented with similar LVEF (60+/-5 vs. 58+/-4%), but DCD cardiac recipients in comparison to DBD recipients had better GLS (-16.5+/-1.7% vs. -15.1+/-1.4%, p=0.04) and better GCS (-25.2+/-4% vs. 20.9+/-3.25, p=0.02). Conclusion DCD and DBD cardiac recipients present with similar systolic LV function at 1-year follow, as assessed by classical echocardiographic parameters. DCD cardiac recipients have better myocardial deformation parameters as assessed by the speckle tracking in comparison to DBD cardiac recipients. Cardiac transplantation from donation after circulatory death (DCD) has been implemented at Papworth hospital since February 2015. Despite encouraging results some concerns may be raised about the impact of the warm ischemia and reperfusion injury on the myocardium status at longer follow-up. Therefore, we aimed to analyse systolic performance of the left ventricle at 1 year follow in DCD and donation after brain death (DBD) cardiac recipients, as assessed by echocardiography with myocardial deformation imaging. We identified 26 DCD cardiac recipients who were transplanted from February 2015 to February 2017 and we matched them with 26 DBD cardiac recipients. Three and 2 patients from DCD and DBD group, respectively, died in the first-year post transplant. In the remaining patients we have compared the classical echocardiographic measurements as well as global longitudinal strain (GLS) and global circumferential strain (GCS) at 1-year follow-up. DCD and DBD patients did not present with differences in terms of classical echocardiographic parameters of left ventricular (LV) structure and systolic function. LVEDV was similar in DCD and DBD patients (102+/-37 vs. 99+/-21 ml, respectively), as well as LVESV (44+/-12 vs. 43 +/- 18 ml, respectively) and LV mass (157+/-36 vs. 169+/-44 gr). LV ejection fraction was similar in two groups (57+/- 7 vs. 58+/-8 %), as well as GLS (-15.9+/-2.3 vs. 14.8+/- 1.9%, p=0.1) and GCS (-23.7+/-5.7 vs. -20.3+/-4.1, p=0.05). In both groups 3 patients presented with left ventricular dysfunction secondary either to primary graft dysfunction or cellular rejection. When we limited analysis to the patients who presented at 1 year follow up with LVEF>=50%, DCD and DBD cardiac recipients presented with similar LVEF (60+/-5 vs. 58+/-4%), but DCD cardiac recipients in comparison to DBD recipients had better GLS (-16.5+/-1.7% vs. -15.1+/-1.4%, p=0.04) and better GCS (-25.2+/-4% vs. 20.9+/-3.25, p=0.02). DCD and DBD cardiac recipients present with similar systolic LV function at 1-year follow, as assessed by classical echocardiographic parameters. DCD cardiac recipients have better myocardial deformation parameters as assessed by the speckle tracking in comparison to DBD cardiac recipients.

Hepatitis C Virus Recurrence Occurs Earlier in Patients Receiving Donation After Circulatory Death Liver Transplant Grafts Compared With Those Receiving Donation After Brainstem Death Grafts

IntroductionHepatitis C virus (HCV)-related cirrhosis remains the commonest indication for liver transplantation worldwide, yet few studies have investigated the impact of donation after circulatory death (DCD) graft use on HCV recurrence and patient outcomes. DCD grafts have augmented the limited donor organ pool and reduced wait-list mortality, although concerns regarding graft longevity and patient outcome persist. MethodsThis was a single-center study of all HCV + adults who underwent DCD liver transplantation between 2004 and 2014. 44 HCV+ patients received DCD grafts, and were matched with 44 HCV+ recipients of donation after brainstem death (DBD) grafts, and their outcomes examined. ResultsThe groups were matched for age, sex, and presence of hepatocellular carcinoma; no significant differences were found between the group's donor or recipient characteristics. Paired and unpaired analysis demonstrated that HCV recurrence was more rapid in recipients of DCD organs compared with DBD grafts (408 vs 657 days; P = .006). There were no significant differences in graft survival, patient survival, or rates of biliary complications between the cohorts despite DCD donors being 10 years older on average than those used in other published experience. ConclusionsIn an era of highly effective direct acting antiviral therapy, rapid HCV recrudescence in grafts from DCD donors should not compromise long-term morbidity or mortality. In the context of rising wait-list mortality, it is prudent to use all available sources to expand the pool of donor organs, and our data support the practice of using extended-criteria DCD grafts based on donor age. Notwithstanding that, clinicians should be aware that HCV recrudescence is more rapid in DCD recipients, and early post-transplant anti-viral therapy is indicated to prevent graft injury.

Clinical outcomes of donation after circulatory death liver transplantation in primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a progressive fibro-inflammatory cholangiopathy for which liver transplantation is the only life-extending intervention. These patients may benefit from accepting liver donation after circulatory death (DCD), however their subsequent outcome is unknown. The aim of this study was to determine the clinical impact of using DCD liver grafts in patients specifically undergoing transplantation for PSC. Clinical outcomes were prospectively evaluated in PSC patients undergoing transplantation from 2006 to 2016 stratified by donor type (DCD, n=35 vs. donation after brainstem death [DBD], n=108). In liver transplantation for PSC; operating time, days requiring critical care support, total ventilator days, incidence of acute kidney injury, need for renal replacement therapy (RRT) or total days requiring RRT were not significantly different between DCD vs. DBD recipients. Although the incidence of ischaemic-type biliary lesions was greater in the DCD group (incidence rate [IR]: 4.4 vs. 0 cases/100-patient-years; p<0.001) there was no increased risk of post-transplant biliary strictures overall (hazard ratio [HR]: 1.20, 0.58-2.46; p=0.624), or in sub-analysis specific to anastomotic strictures or recurrent PSC, between donor types. Graft loss and mortality rates were not significantly different following transplantation with DCD vs. DBD livers (IR: 3.6 vs. 3.1 cases/100-patient-years, p=0.34; and 3.9 vs. 4.7, p=0.6; respectively). DCD liver transplantation in PSC did not impart a heightened risk of graft loss (HR: 1.69, 0.58-4.95, p=0.341) or patient mortality (0.75, 0.25-2.21, p=0.598). Transplantation with DCD (vs. DBD) livers in PSC patients does not impact graft loss or patient survival. In an era of organ shortage, DCD grafts represent a viable therapeutic option for liver transplantation in PSC patients. Lay summary: This study examines the impact of liver transplantation in primary sclerosing cholangitis (PSC) with organs donated after circulatory death (DCD), compared to donation after brainstem death (DBD). We show that in appropriately selected patients, the outcomes for DCD transplantation mirror those using DBD livers, with no significant differences in complication rate, patient survival or transplanted liver survival. In an era of organ shortage and increasing wait-list times, DCD livers represent a potential treatment option for transplantation in PSC.

Decision modeling in donation after circulatory death liver transplantation.

Donation after circulatory death (DCD) liver allografts are increasingly used for transplantation. However, the posttransplantation clinical and quality of life outcomes of DCD recipients are traditionally considered to be inferior compared with donation after brain death (DBD) allograft recipients. Decision making for such marginal organs can be difficult. This study investigated the optimal decision to accept or decline a DCD liver allograft for a patient based on their current health. A Markov decision process model was constructed to predict the 5-year clinical course of patients on the liver transplant waiting list. Clinical outcomes were determined from the UK transplant registry or appropriate literature. Quality-adjusted life years (QALYs) were determined using the condition-specific short form of liver disease quality of life (SF-LDQoL) questionnaire. There were 293/374 (78.3%) eligible patients who completed the SF-LDQoL questionnaire. A total of 73 respondents (24.9%) were before transplant and 220 were after transplant (DBD recipient, 56.3%; DCD recipient, 8.5%; ischemic cholangiopathy patient, 2.4%; retransplant recipient, 7.9%). Predictive modeling indicated that QALYs gained at 5 years were significantly higher in DCD recipients (3.77; 95% confidence interval [CI], 3.44-4.10) compared with those who remained on the waiting list for a DBD transplant with Model for End-Stage Liver Disease (MELD) scores of 15-20 (3.36; 95% CI, 3.28-3.43), or >20 (3.07; 95% CI, 3.00-3.14). There was no significant advantage for individuals with MELD scores <15 (3.55; 95% CI, 3.47-3.63). In conclusion, this model predicts that patients on the UK liver transplant waiting list with MELD scores >15 should receive an offered DCD allograft based on the QALYs gained at 5 years. This analysis only accounts for donor-recipient risk pairings seen in current practice. The optimal decision for patients with MELD scores <15 remains unclear. However, a survival benefit was observed when a DCD organ was accepted. Liver Transplantation 23 594-603 2017 AASLD.

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.

Negative impact of prolonged cold storage time before machine perfusion preservation in donation after circulatory death kidney transplantation.

Kidney grafts are often preserved initially in static cold storage (CS) and subsequently on hypothermic machine perfusion (MP). However, the impact of CS/MP time on transplant outcome remains unclear. We evaluated the effect of prolonged CS/MP time in a single-center retrospective cohort of 59 donation after circulatory death (DCD) and 177 matched donation after brain death (DBD) kidney-alone transplant recipients. With mean overall CS/MP times of 6.0 h/30.0 h, overall incidence of delayed graft function (DGF) was higher in DCD transplants (30.5%) than DBD transplants (7.3%, P < 0.0001). In logistic regression, DCD recipient (P < 0.0001), longer CS time (P = 0.0002), male recipient (P = 0.02), and longer MP time (P = 0.08) were associated with higher DGF incidence. In evaluating the joint effects of donor type (DBD vs. DCD), CS time (<6 vs. ≥6 h), and MP time (<36 vs. ≥36 h) on DGF incidence, one clearly sees an unfavorable effect of MP time ≥36 h (P = 0.003) across each donor type and CS time stratum, whereas the unfavorable effect of CS time ≥6 h (P = 0.01) is primarily seen among DCD recipients. Prolonged cold ischemia time had no unfavorable effect on renal function or graft survival at 12mo post-transplant. Long CS/MP time detrimentally affects early DCD/DBD kidney transplant outcome when grafts were mainly preserved by MP; prolonged CS time before MP has a particularly negative impact in DCD kidney transplantation.