Perspectives on donor-derived infections from Germany.

AIM: Often, organ transplantation is the only option to improve the life expectancy and quality of life of patients with terminal organ failure. Despite improved donor and organ assessment, a residual risk remains for transmitting infection, tumor, or other disease from the donor to recipients. Analysis, reporting, and managing of donor-derived diseases through a vigilance and surveillance system (V&S) is mandatory in many countries. We report on suspected and proven/probable donor-derived infections (DDI) in Germany over a period of 8 years (2016-2023). METHODS: All incoming serious-adverse-event and serious-adverse-reaction (SAE/SAR) reports from 01.01.2016 to 31.12.2023 were evaluated for suspected DDI. Analysis of imputability followed the definition of the US Disease Transmission Advisory Committee (DTAC). Only probable and proven cases according to DTAC classification were defined as DDI. RESULTS: During the study period, 9771 donors in Germany donated post-mortem organs to 27 919 recipients. In that period 612 SAE/SAR cases were reported, 377 (62%) involved infections. 41 cases were proven/probable DDI affecting 58 recipients (seven recipients died, 12%). Suspected infections were bacterial (182/377, 48%), fungal (135/377, 36%), viral (55/377, 15%), and parasitic (5/377, 1%). In case of bacterial DDI, no recipient died, but organ loss occurred in six recipients. In case of fungal or viral DDI, 19% (3/16) and 21% (3/14) of the recipients died, respectively. CONCLUSIONS: DDI are rare in solid organ transplantation (58/27 919, 0.21%), but when they occur, they are associated with high morbidity and mortality in affected recipients. Careful and detailed donor evaluation and a reliable V&S help improve recipient safety.

Vigilance Data in Organ Donation and Solid Organ Transplantation in Germany: Six Years of Experience 2016-2022.

The reporting of serious adverse events (SAE) and serious adverse reactions (SAR) is an essential part of an effective vigilance and surveillance system (V&S) in organ donation and transplantation. All SAE and SAR reported to the German organ procurement organization (DSO) between 2016 and 2022 were analyzed. In case of a possible transmission of a disease to one or more recipients, an assessment of imputability was done according to the grading system of the US Disease Transmission Advisory Committee (DTAC). 543 SAE and SAR cases were reported to the DSO and analyzed in detail. 53 of the 543 reports (9.8%) were proven or probable (P/P) transmissions of infectious diseases, malignancies or other diseases to 75 recipients. Infections were the most frequently reported P/P disease transmission occurrences (30/53, 57%). In case of disease transmission, the mortality of the recipients was high (17/75, 23%), especially when a malignant disease was transmitted (11/22, 50 %). Donor-Derived disease transmission is a rare event (53/8,519; 0.6 %), but when it occurs can lead to significant morbidity and mortality.

Transplantation of donor lungs with pulmonary embolism - a retrospective study.

Lung transplantation from donors with fulminant pulmonary arterial embolism as a cause of death remains controversial. An analysis was performed comparing preoperative characteristics and outcomes of 25 donors with a primary diagnosis of pulmonary arterial embolism to 1085 recipients of donor lungs without pulmonary arterial embolism. No early functional impairment of donor lungs with pulmonary embolism was detectable as depicted by the incidence of primary graft dysfunction immediately after surgery (P = 0.66), 24 (P = 0.79), 48 (P = 0.99) and 72 h (P = 0.99) after transplantation. Pulmonary function testing at 1 year (P = 0.003) and at last outpatient control (P < 0.05) showed superior results in the cohort receiving lungs from donors with pulmonary embolism. Incidence of chronic lung allograft dysfunction (CLAD) showed no difference within the first year after lung transplantation, however, 5 year-CLAD free survival was superior in recipients (70.4% vs. 55.1%, P = 0.006) of donor lungs with pulmonary embolism. Overall survival was similar in both groups. Lungs from donors with fulminant pulmonary embolism prior to brain death can safely be used for lung transplantation without impairing postoperative outcomes. Lung function testing shows favorable midterm results in recipients of donor lungs with pulmonary embolism.

Donor Dopamine Does Not Affect Liver Graft Survival: Evidence of Safety From a Randomized Controlled Trial.

Treatment of donation after brain death (DBD) donors with low-dose dopamine improves the outcomes after kidney and heart transplantation. This study investigates the course of liver allografts from multiorgan donors enrolled in the randomized dopamine trial between 2004 and 2007 (clinicaltrials.gov identifier: NCT00115115). There were 264 hemodynamically stable DBDs who were randomly assigned to receive low-dose dopamine. Dopamine was infused at 4 µg/kg/minute for a median duration of 6.0 hours (interquartile range, 4.4-7.5 hours). We assessed the outcomes of 212 liver transplantations (LTs) performed at 32 European centers. Donors and recipients of both groups were very similar in baseline characteristics. Pretransplant laboratory Model for End-Stage Liver Disease score was not different in recipients of a dopamine-treated versus untreated graft (18 ± 8 versus 20 ± 8; P = 0.12). Mean cold ischemia time was 10.6 ± 2.9 versus 10.1 ± 2.8 hours (P = 0.24). No differences occurred in biopsy-proven rejection episodes (14.4% versus 15.7%; P = 0.85), requirement of hemofiltration (27.9% versus 31.5%; P = 0.65), the need for early retransplantation (5.8% versus 6.5%; P > 0.99), the incidence of primary nonfunction (7.7% versus 8.3%; P > 0.99), and in-hospital mortality (15.4% versus 14.8%; P > 0.99). Graft survival was 71.2% versus 73.2% and 59.6% versus 62.0% at 2 and 3 years (log-rank P = 0.71). Patient survival was 76.0% versus 78.7% and 65.4% versus 69.4% at 1 and 3 years (log-rank P = 0.50). In conclusion, donor pretreatment with dopamine has no short-term or longterm effects on outcome after LT. Therefore, low-dose dopamine pretreatment can safely be implemented as the standard of care in hemodynamically stable DBDs.

High-urgency kidney transplantation in the Eurotransplant Kidney Allocation System: success or waste of organs? The Eurotransplant 15-year all-centre survey.

BACKGROUND: In the Eurotransplant Kidney Allocation System (ETKAS), transplant candidates can be considered for high-urgency (HU) status in case of life-threatening inability to undergo renal replacement therapy. Data on the outcomes of HU transplantation are sparse and the benefit is controversial. METHODS: We systematically analysed data from 898 ET HU kidney transplant recipients from 61 transplant centres between 1996 and 2010 and investigated the 5-year patient and graft outcomes and differences between relevant subgroups. RESULTS: Kidney recipients with an HU status were younger (median 43 versus 55 years) and spent less time on the waiting list compared with non-HU recipients (34 versus 54 months). They received grafts with significantly more mismatches (mean 3.79 versus 2.42; P < 0.001) and the percentage of retransplantations was remarkably higher (37.5 versus 16.7%). Patient survival (P = 0.0053) and death with a functioning graft (DwFG; P < 0.0001) after HU transplantation were significantly worse than in non-HU recipients, whereas graft outcome was comparable (P = 0.094). Analysis according to the different HU indications revealed that recipients listed HU because of an imminent lack of access for dialysis had a significantly worse patient survival (P = 0.0053) and DwFG (P = 0.0462) compared with recipients with psychological problems and suicidality because of dialysis. In addition, retransplantation had a negative impact on patient and graft outcome. CONCLUSIONS: Facing organ shortages, increasing wait times and considerable mortality on dialysis, we question the current policy of HU allocation and propose more restrictive criteria with regard to individuals with vascular complications or repeated retransplantations in order to support patients on the non-HU waiting list with a much better long-term prognosis.

Impact of dynamic changes in MELD score on survival after liver transplantation - a Eurotransplant registry analysis.

BACKGROUND & AIMS: With restricted numbers of available organs, futility in liver transplantation has to be avoided. The concept of dynamic changes in MELD score (DeltaMELD) has previously been shown to be a simple tool to identify patients with the greatest risk of death after transplantation. Aim was to validate this concept with the Eurotransplant (ET) database. METHODS: A retrospective registry analysis was performed on all patients listed for liver transplantation within ET between 2006 and 2011. Patients <18 years of age, acute liver failure, malignancy and patients listed for retransplantation were excluded. Influence of MELD at listing (MELDon), MELD at transplantation (MELDoff), DeltaMELD, age, sex, underlying disease and time on the waiting list on overall survival after liver transplantation were evaluated. RESULTS: A total of 16 821 patients were listed for liver transplantation, 8096 met the inclusion criteria. Age, MELD on and DeltaMELD showed significant influence on survival on the waiting list. Age and DeltaMELD showed influence on survival after liver transplantation, with DeltaMELD>10 showing a 1.6-fold increased risk of death. CONCLUSION: The concept of DeltaMELD was validated in a large, prospective data set. It provides a simple tool to identify patients with increased risk of death after liver transplantation and might help improve long-term results.

Why offered pancreases are refused in the allocation process-a descriptive study using routine data from eurotransplant.

BACKGROUND: The majority of pancreases, offered in allocation, are discarded. This pancreas underutilization is not well understood yet. METHODS: We analyzed the detailed allocation protocols of all Eurotransplant-registered German whole-pancreas donors (2005-2009; n=1758). Outcome measures included donor characteristics, number of refusals per organ, and proportion of different refusal reasons in the whole sample and subgroups. RESULTS: Thirty-seven percent of offered pancreases were transplanted; among these, 62% of pancreases were of potentially high quality (favorable donor age and pre-procurement pancreas allocation suitability score, no malignancy, n=290). A pancreas was placed after four offers (median) or withdrawn after eight offers (median). Seventy-five percent of refusal reasons were donor related (e.g., "lab results", "age", "macroscopy", and "long intensive care unit [ICU] stay"). Among pancreases refused for "diabetes" or "malignancy" at least once, the proportion of transplanted organs was less than 10%; pancreases refused due to "trauma", "age", or "resuscitation" were later transplanted in 48%, 32%, and 28%, respectively. The impact of donor age and ICU stay on organ refusal varied substantially: organs were refused due to length of ICU stay even if donors stayed 7 days or less; some organs were transplanted without ever being refused due to ICU stay in donors who stayed 8 days or more in ICU. There were no clinically significant disparities between donors of used and unused pancreases, except age (median, 31 vs. 42 years). DISCUSSION: The loss of several pancreases seems avoidable. Many refusal reasons are not plausible, because there is no evidence supporting the refusal and because many of these organs were transplanted by other centers. This increases inefficiency in the allocation system.

Donor scoring system for heart transplantation and the impact on patient survival.

BACKGROUND: The aim of this study was to design and validate a heart donor score that reflects experts' perceived risk of allograft failure. METHODS: All heart donors reported to Eurotransplant between January 1, 2005 and December 31, 2008 (N = 4,110) were used to create a donor score. Based on observed discard rates and using multivariate regression, points were assigned for the following donor factors: age; cause of death; body mass index (BMI); diabetes mellitus (DM); duration of ICU stay; compromised history (drug, abuse, sepsis, meningitis, malignancy, HBsAg(+) or anti-HCV(+)); hypertension; cardiac arrest; echocardiography; coronary angiogram; serum sodium; and noradrenaline and dopamine/dobutamine doses. The donor score was obtained by adding all points. All heart donors reported to Eurotransplant in 2009 were included to validate the score (N = 885). RESULTS: All donor factors, except BMI, DM and duration of ICU stay, significantly predicted discard. Based on the median value of the score, donors were classified into low-risk donors (LRDs: ≤16 points) and high-risk donors (HRDs: ≥17 points). In the validation set, discard rates were significantly different when comparing HRDs (35%) and LRDs (7%) (p < 0.0001). In addition, the heart donor score was significantly associated with 3-year survival: LRD 81.5% vs HRD 70.0% (p = 0.004). CONCLUSIONS: The heart donor score accurately reflects the likelihood of organ acceptance and predicts long-term patient mortality. Application of this score at time of donor reporting may facilitate donor risk assessment and allow for more appropriate matching of extended criteria donor hearts.

Living donor liver transplantation in adults in the MELD era in Germany--a multi-center retrospective analysis.

The aim of this analysis was to provide an update on the current trend in living donor liver transplantation (LDLT) for adult recipients in the model of end stage liver disease (MELD) era in Germany and to encourage a wider implementation of LDLT. We descriptively analysed the data of LDLTs in Germany from 15 December 2006 to 31 December 2009 using a multi-center retrospective analysis via a questionnaire and data provided by Eurotransplant. Ten German centers performed LDLTs in adults. Eighty four transplantations in 50 male recipients and 34 female recipients were performed during the review period, ranging from 1 to 16 LDLTs per center. Hepatocellular carcinoma in cirrhosis (15/84) was the most common transplantation indication. The recipient mean lab-MELD score was 15 (±8). Six re-transplantations were necessary after initial LDLTs. The 1-year patient survival was 81%. We obtained data of 79/84 donors. The incidence of complications was 30.4% (n = 24). There were no grade 5 complications according to the Clavien classification. LDLT is an established treatment option that may reduce the waiting time, provides high quality split liver grafts and should be advocated in the MELD era to reduce organ shortage and 'death on the waiting list'.

Systemic complement activation in deceased donors is associated with acute rejection after renal transplantation in the recipient.

BACKGROUND: Acute rejection after renal transplantation has been shown to be negatively associated with long-term graft survival. Identifying donor factors that are associated with acute rejection in the recipient could help to a better understanding of the relevant underlying processes that lead to graft injury. Complement activation has been shown to be an important mediator of renal transplant related injury. In this study, we analyzed the effect of systemic complement activation in deceased donors before transplantation of their kidneys on posttransplant outcome in the recipient. METHODS: Plasma from 232 deceased brain-dead and deceased cardiac-dead donors were analyzed for the complement activation markers C5b-9, C4d, Bb, and complement component mannan binding lectin by ELISA. The association of these parameters with posttransplant outcome in recipients was analyzed in a multivariate regression model. RESULTS: It was found that C5b-9 level in donor plasma is associated with biopsy-proven acute rejection in the recipient during the first year after renal transplantation (P = 0.035). Both in deceased brain-dead and deceased cardiac-dead donors increased complement activation was found. CONCLUSIONS: In conclusion, we found C5b-9 in the donor to be associated with acute rejection of renal transplants in the recipient. Whether targeting complement activation in the donor may ameliorate acute rejection in the recipient needs to be studied.

Defining an extended criteria donor lung: an empirical approach based on the Eurotransplant experience.

The aim of this study was to design and validate a lung donor score that reflects experts' perceived risk of allograft failure. All lung donors reported to Eurotransplant from 1999 to 2007 [N=6080] were used to create a lung donor score. Based on observed discard rates and using multivariate regression, points were assigned for six preprocurement donor variables. Donors reported in 2008 were used to validate the score [N=751]. All the six factors significantly predicted discard; as an example, the following donor with points: age 55-59years: 2; compromised history: 4; smoking: 2; shadow on chest X-ray: 2; purulent secretion during bronchoscopy: 2; and Pao(2) /Fio(2) ratio below 300mmHg: 3. Discard rates for donors with a lung donor score of 6 points (class 1) was 18%, while 36% and 54% of the donors with a score of 7-8 (class 2) and 9+(class 3) were discarded (P<0.001), respectively. In addition, the donor lung score was significantly associated with 1-year survival: class 1: 91%; class 2: 80%; and class 3: 72% (P=0.017). The lung donor score accurately reflects the likelihood of organ acceptance and predicts patient mortality, and its application at time of donor reporting may facilitate donor risk assessment and patient selection.

Machine perfusion versus cold storage for the preservation of kidneys donated after cardiac death: a multicenter, randomized, controlled trial.

OBJECTIVE: Hypothermic machine perfusion may improve outcome after transplantation of kidneys donated after cardiac death (DCD), but no sufficiently powered prospective studies have been reported. Because organ shortage has led to an increased use of DCD kidneys, we aimed to compare hypothermic machine perfusion with the current standard of static cold storage preservation. METHODS: Eighty-two kidney pairs from consecutive, controlled DCD donors 16 years or older were included in this randomized controlled trial in Eurotransplant. One kidney was randomly assigned to machine perfusion and the contralateral kidney to static cold storage according to computer-generated lists created by the permuted block method. Kidneys were allocated according to standard rules, with concealment of the preservation method. Primary endpoint was delayed graft function (DGF), defined as dialysis requirement in the first week after transplantation. All 164 recipients were followed until 1 year after transplantation. RESULTS: Machine perfusion reduced the incidence of DGF from 69.5% to 53.7% (adjusted odds ratio: 0.43; 95% confidence interval 0.20-0.89; P = 0.025). DGF was 4 days shorter in recipients of machine-perfused kidneys (P = 0.082). Machine-perfused kidneys had a higher creatinine clearance up to 1 month after transplantation (P = 0.027). One-year graft and patient survival was similar in both groups (93.9% vs 95.1%). CONCLUSIONS: Hypothermic machine perfusion was associated with a reduced risk of DGF and better early graft function up to 1 month after transplantation. Routine preservation of DCD kidneys by hypothermic machine perfusion is therefore advisable.

Early renal failure after domino liver transplantation using organs from donors with primary hyperoxaluria type 1.

BACKGROUND: Organ shortage is responsible for high mortality rates of patients awaiting liver transplantation (LT). Domino transplantation has had reported success in patients with metabolic disorders. Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder. There are a few case reports that suggest that PH1 livers originating from donors that have undergone combined liver-kidney transplantation can be successfully used for domino transplantation. METHODS: In the last decade, five patients received a domino liver transplant from patients with PH1 in the EUROTRANSPLANT region. In this study, we report the clinical course and outcome of these five patients who were received a domino graft transplant. RESULTS: All patients, with the exception of one, suffered from multifocal hepatocellular carcinoma and underwent domino LT from patients undergoing combined liver-kidney transplantation for PH1. Within the first 4 weeks, all the domino recipients developed dialysis-dependent kidney failure despite good liver function. Four of the five patients died. The only survivor underwent retransplantation due to hepatic artery thrombosis. Twenty months after transplantation, this patient is doing well and has had no recurrence of hepatocellular carcinoma. CONCLUSION: Domino LT using donors with PH1 results in early renal failure and cannot be recommended for transplantation unless preventive strategies have been identified.