German Transplant Research Articles

Walter Brendel and the dawn of transplantation research in Germany.

Walter Brendel was a physiologist who headed the Institut of Experimental Surgery at the University of Munich (LMU) from 1961 until 1989. His legendary career began with the development of an anti-human lymphocyte globulin (ALG) at his Institute during the late 1960s. The initial successful treatment of a small number of patients culminated in the co-treatment of the first successfully heart-transplanted patient in Capetown, South Africa (successful reversal with ALG of an acute allograft rejection). Walter Brendel was a pioneering personality whose work has laid a wide platform for the promotion of interdisciplinarily conducted innovative research programs in various domains of translational science and medicine. Among the many innovative achievements, the most notable are: discovery of involvement of the alternative pathway of complement activation in hyperacute xenograft rejection; induction of immunological tolerance to horse IgG as a means to prevent anaphylactic reactions during ALG therapy; development and clinical implementation of the extracorporeal shock wave lithotripsy for extracorporeal destruction of renal and ureteral calculi. The legacy of Brendel continues with the foundation of the Walter-Brendel Kolleg für Transplantationsmedizin (i.e., the German Transplant School for Transplantation Medicine), which has been held annually since 1994.

Multinational Analysis of Marginal Liver Grafts Based on the Eurotransplant Extended Donor Criteria.

To evaluate the outcome of marginal liver grafts based on the Eurotransplant extended criteria donor (ECD) criteria. Eurotransplant uses a broad definition of ECD criteria (age >65 years, steatosis >40%, body mass index >30kg/m 2 , intensive care unit stay >7 days, donation after circulatory death, and certain laboratory parameters) for allocating organs to recipients who have consented to marginal grafts. Historically, marginal liver grafts were associated with increased rates of dysfunction. Retrospective cohort analysis using the German Transplant Registry and the U.S. Scientific Registry of Transplant Recipients (SRTR) from 2006 to 2016. Results were validated with recent SRTR data (2017-2022). Donors were classified according to the Eurotransplant ECD criteria, donation after circulatory death was excluded. Data were analyzed with cutoff prediction, binomial logistic regression, and multivariate Cox regression. The study analyzed 92,330 deceased brain-dead donors (87% SRTR) and 70,374 transplants (87% SRTR) in adult recipients. Predominant ECD factors were donor age in Germany (30%) and body mass index in the United States (28%). Except for donor age, grafts meeting ECD criteria were not associated with impaired 1 or 3-year survival. Cutoffs had little to no predictive value for 30-day graft survival (area under the receiver operating curve: 0.49-0.52) and were nominally higher for age (72 vs 65 years) in Germany as compared with those defined by current Eurotransplant criteria. The outcome of transplanted grafts from higher risk donors was nearly equal to standard donors with Eurotransplant criteria failing to predict survival of marginal grafts. Modifying ECD criteria could improve graft allocation and potentially expand the donor pool.

Shortfalls of new data 2017-2020 in the German transplant registry

Shortfalls of new data 2017-2020 in the German transplant registry

Hope for motherhood: pregnancy after allogeneic hematopoietic cell transplantation (a national multicenter study)

AbstractImproved long-term survival rates after allogeneic hematopoietic cell transplantation (alloHCT) make family planning for young adult cancer survivors an important topic. However, treatment-related infertility risk poses challenges. To assess pregnancy and birth rates in a contemporary cohort, we conducted a national multicenter study using data from the German Transplant Registry, focusing on adult women aged 18 to 40 years who underwent alloHCT between 2003 and 2018. Of 2654 women who underwent transplantation, 50 women experienced 74 pregnancies, occurring at a median of 4.7 years after transplant. Fifty-seven of these resulted in live births (77%). The annual first birth rate among HCT recipients was 0.45%, which is >6 times lower than in the general population. The probability of a live birth 10 years after HCT was 3.4%. Factors associated with an increased likelihood of pregnancy were younger age at alloHCT, nonmalignant transplant indications, no total body irradiation or a cumulative dose of <8 Gy, and nonmyeloablative/reduced-intensity conditioning. Notably, 72% of pregnancies occurred spontaneously, with assisted reproductive technologies used in the remaining cases. Preterm delivery and low birth weight were more common than in the general population. This study represents the largest data set reporting pregnancies in a cohort of adult female alloHCT recipients. Our findings underscore a meaningful chance of pregnancy in alloHCT recipients. Assisted reproductive technologies techniques are important and funding should be made available. However, the potential for spontaneous pregnancies should not be underestimated, and patients should be informed of the possibility of unexpected pregnancy despite reduced fertility. Further research is warranted to understand the impact of conditioning decisions on fertility preservation.

Does Timepoint of Surgical Procedure Affect the Outcome in Simultaneous Pancreas-Kidney Transplantation? A Retrospective Single-Center Analysis over 20 Years.

Background: Sleep deprivation and disturbances in circadian rhythms may hinder surgical performance and decision-making capabilities. Solid organ transplantations, which are technically demanding and often begin at uncertain times, frequently during nighttime hours, are particularly susceptible to these effects. This study aimed to assess how transplant operations conducted during daytime versus nighttime influence both patient and graft outcomes and function. Methods: simultaneous pancreas-kidney transplants (SPKTs) conducted at the University Hospital of Leipzig from 1998 to 2018 were reviewed retrospectively. The transplants were categorized based on whether they began during daytime hours (8 a.m. to 6 p.m.) or nighttime hours (6 p.m. to 8 a.m.). We analyzed the demographics of both donors and recipients, as well as primary outcomes, which included surgical complications, patient survival, and graft longevity. Results: In this research involving 105 patients, 43 SPKTs, accounting for 41%, took place in the daytime, while 62 transplants (59%) occurred at night. The characteristics of both donors and recipients were similar across the two groups. Further, the rate of (surgical) pancreas graft-related complications and reoperations (daytime 39.5% versus nighttime 33.9%; p = 0.552) were also not statistically significant between both groups. In this study, the five-year survival rate for patients was comparable for both daytime and nighttime surgeries, with 85.2% for daytime and 86% for nighttime procedures (p = 0.816). Similarly, the survival rates for pancreas grafts were 75% for daytime and 77% for nighttime operations (p = 0.912), and for kidney grafts, 76% during the day compared to 80% at night (p = 0.740), indicating no significant statistical difference between the two time periods. In a multivariable model, recipient BMI > 30 kg/m2, donor age, donor BMI, and cold ischemia time > 15 h were independent predictors for increased risk of (surgical) pancreas graft-related complications, whereas the timepoint of SPKT (daytime versus nighttime) did not have an impact. Conclusions: The findings from our retrospective analysis at a big single German transplant center indicate that SPKT is a reliable procedure, regardless of the start time. Additionally, our data revealed that patients undergoing nighttime transplants have no greater risk of surgical complications or inferior results concerning long-term survival of the patient and graft. However, due to the small number of cases evaluated, further studies are required to confirm these results.

Clinical Features, Diagnostics, Etiology, and Outcomes of Hospitalized Solid Organ Recipients With Community-Acquired Pneumonia: A Retrospective Cohort Analysis

BackgroundCommunity-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Limited evidence is available on the most effective diagnostic approaches, management strategies, and long-term outcomes for CAP in patients who have undergone solid organ transplantation. Research QuestionWhat is the acute and long-term morbidity and mortality after CAP in organ transplant recipients? Study Design and MethodsWe retrospectively analysed hospitalisations for CAP in solid organ recipients at the largest German transplant centre. The study included patients admitted between 1 January 2010 and 31 May 2021. The reported outcomes are in-hospital and 1-year mortality, risk of cardiovascular events during hospitalisation and at one year, admission to the intensive care unit, and risk of pneumonia with P. aeruginosa. Multivariable binary logistic regression using stepwise forward selection was performed to determine predictive factors for pneumonia with P. aeruginosa. ResultsWe analysed data from 403 hospitalisations of 333 solid organ recipients. In over 60% of cases, patients had multiple comorbidities, with cardiovascular and chronic kidney disease being the most prevalent. More than half of the patients required oxygen supplementation after admission. In-hospital mortality (13.2%) and the death rate at one year post-event (24.6%) were higher than data reported from immunocompetent patients. We also observed high rates of acute cardiovascular events and events occurring one year after admission. Early blood cultures and bronchoscopy in the first 24 hours significantly increased the odds of establishing an aetiology. In our low-resistance setting, the burden of antimicrobial resistance was driven by bacteria from chronically colonised patients, mostly lung transplant recipients. InterpretationThis comprehensive analysis highlights the high morbidity associated with CAP after transplantation. It also emphasises the need for prospective multicenter studies to guide evidence-based practices and improve outcomes for these vulnerable patients.

The German Transplant Registry - An Analysis of Legacy Data 2006-2016

In 2018, medical transplant data from three institutions were merged to create a German transplant registry. Since June 2021, access to data of the registry has been available. It was planned to analyze the registry data in order to compare special allocation rules with regular allocation for heart, liver, lung, and kidney transplantation. Our approach led to a quality analysis of the registry. Upon request, legacy data (2006-2016) of the registry was provided, divided into 61 elements. From these elements, the user had to compile the required dataset. Data checks were performed for completeness, correct allocation of information, and consistency among different sources. Software used for these tasks included R, SQL, and Excel. The initial elements ("waiting list" elements) of the four types of transplantations contained data from a total of 80,259 originally listed patients. However, these patients were only partially present in other elements resulting in complete datasets reflecting waiting time in only 23%, 30%, 50%, and 96%, and for post-transplantation outcomes in 14%, 11%, 38%, and 13% (heart, liver, lung, and kidney transplantation, respectively). The linking of urgency information with clinical data was successful in only a small proportion, with only 6% for heart transplantation. Incorrect and thus implausible allocations in the case of special allocation rules indicated incorrect entries in the registry. Data from different data providers were inconsistent. The incompleteness and incorrect data allocation raise doubts about the reliability of scientific studies based on the transplant registry. The complex structure also hinders the compilation of a reliable dataset, which is uncommon internationally. New data (acquisition since 2017) has only been available since December 2023. The transplant registry urgently needs restructuring. Competent clinical data management, involving transplant medical expertise, and continuous quality controls are essential in this process.

Smart Conditioning with Venetoclax-Enhanced Sequential FLAMSA + RIC in Patients with High-Risk Myeloid Malignancies

Up to 50% of patients with high-risk myeloid malignancies die of relapse after allogeneic stem cell transplantation. Current sequential conditioning regimens like the FLAMSA protocol combine intensive induction therapy with TBI or alkylators. Venetoclax has synergistic effects to chemotherapy. In a retrospective survey among German transplant centers, we identified 61 patients with myeloid malignancies that had received FLAMSA-based sequential conditioning with venetoclax between 2018 and 2022 as an individualized treatment approach. Sixty patients (98%) had active disease at transplant and 74% had genetic high-risk features. Patients received allografts from matched unrelated, matched related, or mismatched donors. Tumor lysis syndrome occurred in two patients but no significant non-hematologic toxicity related to venetoclax was observed. On day +30, 55 patients (90%) were in complete remission. Acute GvHD II°–IV° occurred in 17 (28%) and moderate/severe chronic GvHD in 7 patients (12%). Event-free survival and overall survival were 64% and 80% at 1 year as well as 57% and 75% at 2 years, respectively. The off-label combination of sequential FLAMSA-RIC with venetoclax appears to be safe and highly effective. To further validate these insights and enhance the idea of smart conditioning, a controlled prospective clinical trial was initiated in July 2023.

COVID-19 Outcomes in Kidney Transplant Recipients in a German Transplant Center.

Kidney transplant recipients (KTRs) show higher morbidity and mortality from COVID-19 than the general population and have an impaired response to vaccination. We analyzed COVID-19 incidence and clinical outcomes in a single-center cohort of approximately 2500 KTRs. Between 1 February 2020 and 1 July 2022, 578 KTRs were infected with SARS-CoV-2, with 25 (4%) recurrent infections. In total, 208 KTRs (36%) were hospitalized, and 39 (7%) died. Among vaccinated patients, infection with the Omicron variant had a mortality of 2%. Unvaccinated patients infected with the Omicron variant showed mortality (9% vs. 11%) and morbidity (hospitalization 52% vs. 54%, ICU admission 12% vs. 18%) comparable to the pre-Omicron era. Multivariable analysis revealed that being unvaccinated (OR = 2.15, 95% CI [1.38, 3.35]), infection in the pre-Omicron era (OR = 3.06, 95% CI [1.92, 4.87]), and higher patient age (OR = 1.04, 95% CI [1.03, 1.06]) are independent risk factors for COVID-19 hospitalization, whereas a steroid-free immunosuppressive regimen was found to reduce the risk of COVID-19 hospitalization (OR = 0.51, 95% CI [0.33, 0.79]). This suggests that both virological changes in the Omicron variant and vaccination reduce the risk for morbidity and mortality from COVID-19 in KTRs. Our data extend the knowledge from the general population to KTRs and provide important insights into outcomes during the Omicron era.

A revealing scandal: The German transplant scandal between structural failures, moralizing rules, and ambivalent manipulations

IntroductionIn 2012, the German transplant scandal was uncovered and reported in the national and international media. This article offers an anthropological analysis of the scandal and examines its ‘scandalous’ characteristics by taking a close look at its extraordinary and ordinary features. MethodsThe article is based on ethnographic research using multiple methods including participant observation, interviewing as well as media and document analysis. ResultsThe transplant scandal in Germany revealed systemic ‘scandalous’ features of the national transplant system. From a significant lack of transparency in decision making, a weak legal framework for accountability, adherence to moralizing rules about alcohol and abstinence, to media coverage that individualized the scandal. ConclusionsLooking at extraordinary events such as transplant scandals from an anthropological perspective offers an analysis that goes beyond the singular, scandalous event. An anthropological analysis allows to highlight the ordinary and ambivalent ‘scandalous’ features of transplant medicine It examines transplant medicine at the intersection of biomedicine, politics, and morality.

Control and care structures at transplant centers for patients with ethyltoxic cirrhosis while waiting for a liver transplant: A qualitative survey of practitioners.

The aim of this study was to record the current care and control structures in place for patients with ethyltoxic liver cirrhosis while being prepared for a liver transplant (LTX) at German transplant centers. In addition, it was also intended to analyze the associated barriers as well as the view of the practitioners on ways to improve care of this patient group. In an exploratory descriptive qualitative design, 11 interviews with practitioners from 10 of the 22 German LTX centers were conducted and analyzed using qualitative content analysis. There were considerable differences in the care and control structures in place at the LTX centers. Addiction therapy counseling or treatment were not integrated into the treatment concept at all centers. Structural barriers arose from insufficient funding and staffing. Practitioners recommended expansion of treatment options as well as standardizing treatment concepts. The results of our study point to a need for action both in the area of the structures of the individual LTX centers and overall at the system level. Taking into account current standards of addiction medicine, our results could serve as a basis for the development of treatment concepts and recommendations for optimizing standard care before LTX.

The dual role dilemma of liver transplantation health care professionals

BackgroundSimilar to many other countries, in Germany patients with alcohol-related liver disease are obliged to prove their abstinence before being accepted on a waitlist for liver transplantation. Health care professionals (HCPs) must both treat patients and ensure that patients have proven their abstinence. The aim of this exploratory study was to develop a deeper understanding of how HCPs deal with this dual role.MethodsThe study used semi-structured interviews as the source of data. 11 healthcare professionals from ten of the 22 German transplant centers were interviewed. After transcription, a qualitative content analysis was performed.ResultsWe found that these HCPs faced an ethical dilemma, as they must balance the roles of being both a treatment provider (the therapist role) and an assessor (the monitoring role). To solve this dilemma, the strategy seems to be a tendency for the HCPs to take on one dominant role amongst these two roles. HCPs who prefer to take on the therapist role seem to feel burdened by the 6-month abstinence rule and the obligation to monitor their patients. HCPs who prefer to take on the monitoring role tend to have negative assumptions about the patients. HCPs also reported the impression that patients perceive HCPs as more involved in monitoring and less open to the therapeutic role. From this it can be deduced that current regulations and structures lead both to stress for HCPs and to suboptimal therapy for those affected.ConclusionsThe results showed that current transplantation guidelines can have a negative impact on both patient care and the burdens on the HCPs. From our point of view, there are various changes that could be made to the current clinical practice that would help solve this dilemma. For instance, integrating other assessment criteria that are more closely adapted to the health status trajectory and psychosocial background of the individual patient would be both possible and would lead to improvements in practice.

EnGraft: a multicentre, open-label, randomised, two-arm, superiority study protocol to assess bioavailability and practicability of Envarsus® versus Advagraf™ in liver transplant recipients

BackgroundGraft rejection and chronic CNI toxicity remain obstacles to organ transplant success. Current formulations of tacrolimus, such as Prograf® and Advagraf™, exhibit limitations in terms of pharmacokinetics and tolerability, related in part to suboptimal bioavailability. As dosing non-compliance can result in graft rejection, the once daily formulation of tacrolimus, Advagraf™, was developed (vs 2x/day Prograf®). Benefits of Advagraf™ are counterbalanced by delayed achievement of therapeutic trough levels and need for up to 50% higher doses to maintain Prograf®-equivalent troughs. Envarsus® is also a prolonged-release once-daily tacrolimus formulation, developed using MeltDose™ drug-delivery technology to increase drug bioavailability; improved bioavailability results in low patient drug absorption variability and less pronounced peak-to-trough fluctuations. In phase III de novo kidney transplant studies, Envarsus® proved non-inferior to twice-daily tacrolimus; however, no phase IV studies show superiority of Envarsus® vs Advagraf™ in de novo liver transplant (LTx) recipients.MethodsThe EnGraft compares bioavailability and tests superiority of Envarsus® (test arm) versus Advagraf™ (comparator arm) in de novo LTx recipients. A total of 268 patients from 15 German transplant centres will be randomised 1:1 within 14 days post-LTx. The primary endpoint is dose-normalised trough level (C/D ratio) measured 12 weeks after randomisation. Secondary endpoints include the number of dose adjustments, time to reach first defined trough level and incidence of graft rejections. Additionally, clinical and laboratory parameters will be assessed over a 3-year period.DiscussionC/D ratio is an estimate for tacrolimus bioavailability. Improving bioavailability and increasing C/D ratio using Envarsus could reduce renal dysfunction and other tacrolimus-related toxicities; previous trials have shown that a higher C/D ratio (i.e. slower tacrolimus metabolism) is not only associated with improved renal function but also linked to reduced neurotoxic side effects. A higher C/D ratio could improve clinical outcomes for LTx recipients; EnGraft has begun, with one third of patients recruited by January 2022.Trial registrationThis trial has been registered (4 May 2020) in the EU Clinical Trials Register, EudraCT-Nummer: 2020–000796-20. Additionally, this trial has been registered (22 January 2021) at ClinicalTrials.gov: NCT04720326. The trial received a favourable opinion from the concerned lead ethics committee at the University of Regensburg, under the reference 20–1842-112.

The Tacrolimus Concentration/Dose Ratio Does Not Predict Early Complications After Kidney Transplantation.

Early-on post kidney transplantation, there is a high risk of graft rejection and opportunistic viral infections. A low tacrolimus concentration/dose (C/D) ratio as a surrogate marker of fast tacrolimus metabolism has been established for risk stratification 3months post-transplantation (M3). However, many adverse events occurring earlier might be missed, and stratification at 1month post-transplantation (M1) has not been investigated. We retrospectively analyzed case data from 589 patients who had undergone kidney transplantation between 2011 and 2021at three German transplant centers. Tacrolimus metabolism was estimated by use of the C/D ratio at M1, M3, M6, and M12. C/D ratios increased substantially during the year, particularly between M1 and M3. Many viral infections and most graft rejections occurred before M3. Neither at M1 nor at M3 was a low C/D ratio associated with susceptibility to BKV viremia or BKV nephritis. A low C/D ratio at M1 could not predict acute graft rejections or impaired kidney function, whereas at M3 it was significantly associated with subsequent rejections and impairment of kidney function. In summary, most rejections occur before M3, but a low C/D ratio at M1 does not identify patients at risk, limiting the predictive utility of this stratification approach.

(420) Covid-19 after Heart Transplantation: Treatment and Outcome in a German Transplant Centre

(420) Covid-19 after Heart Transplantation: Treatment and Outcome in a German Transplant Centre

Human Leucocyte Antigen–Matching Can Improve Long Term Outcome of Renal Allografts from Donors Older Than 75 Years

BackgroundRenal transplantation is the therapy of choice for kidney failure. The Eurotransplant Senior Program (ESP) has been established to allocate kidneys ≥65 years to recipients of the same age group considered a regional allocation with short cold ischemia (CIT) but not human-leukocyte-antigen (HLA)-matching. The acceptance of organs aged ≥75 years is also still controversial within the ESP. MethodsIn a multicenter approach, 179 kidney grafts ≥75 years (mean donor age 78 years) that were transplanted in 174 patients in 5 German transplant centers were analyzed. The primary focus of the analysis was long-term outcome of the grafts and the impact of CIT, HLA matching, and recipient related risk factors. ResultsThe mean graft survival was 59 months (median 67 months) with a mean donor age of 78.3 ± 2.9 years. Grafts with 0 to 3 HLA-mismatches had a significantly better overall graft survival compared to grafts with ≥4 mismatches (69 months vs 54 months; P = .008). The mean CIT was short (11.9 ± 5.3 hours) and had no impact on graft survival. ConclusionRecipients receiving a kidney graft from donors aged ≥75 years can benefit from nearly 5 years of survival with a functioning graft. Even minimal HLA matching may improve long term allograft survival.

Presence of Measurable Residual Disease in NPM1 Positive AML in Remission Pre-Transplant Does Not Impact on Survival after Allogeneic Hematopoietic Stem Cell Transplantation

Due to their biological and clinical features, acute myeloid leukemia (AML) with Nucleophosmin-1 (NPM1) gene mutations represents a distinct entity within the WHO classification 2022. As per ELN classification, they are mainly categorized either as favorable or intermediate-risk disease, and as such patients are referred for allogeneic hematopoietic stem cell transplantation (allo-HSCT) at disease relapse, during CR1 or, less frequently, due to primary refractoriness. However, even when transplanted, relapse remains the most common cause of treatment failure. Besides conditioning intensity, presence of measurable residual disease (MRD) at time of allo-HSCT has recently been shown to be associated with an increased risk of relapse post-transplant. Yet, the reported effect might vary according to genetic and immunophenotypic diversity of the disease, transplant setting and MRD technology used. Here, we aim to determine the impact of NPM1 presence assessed via qPCR on post allo-HSCT outcomes. This retrospective study included adult AML patients harboring an NPM1 mutation (NPM1mut) who received a first allo-HSCT between January 2011 and January 2022 at four German transplant centers. NPM1 mutation status was assessed at diagnosis, and monitored throughout the treatment course by qPCR. NPM1 MRD monitoring was performed as previously described (Papadaki et al., 2009, sensitivity of 10−6). MRD status pre-transplant was correlated with outcome. There were no restrictions regarding donor type or conditioning intensity We identified 161 adult AML patients with available pre-transplant MRD status. Median age of the entire cohort was 55 years (21-75). The majority of patients (86%) had cytogenetically normal AML and presented in hematologic remission (CR1, CR2) (69%) at time of allo-HSCT. Whereas NPM1mut was measurable in all patients with active disease, 85/111 (77%) patients in remission had either NPM1mut persistence after antecedent induction/consolidation therapy (n=68) or molecular relapse (n=17). Conditioning intensity used was RIC in 57, MAC in 12, sequential-RIC in 88 and sequential-MAC in 4 patients. Most patients (n=90) were transplanted from matched unrelated donor (matched related: n=37, haploidentical: n=34), using preferentially PBSCs as graft source (n=146). At a median follow-up of 28 months (3-127), the estimated probability of OS and LFS at 2 years was 63% and 55%, respectively. When patients are stratified into groups with active disease, vs NPM1+CR vs NPM1- CR, 2-year OS and LFS show a significant difference (45% vs. 73% vs. 71%; p=0.002 and 55% vs. 62% vs. 67% p=0.005, respectively). Yet, if considering only patients in remission, no survival difference according to NPM1-MRD status at transplantation was detected (OS, p=0.49 and LFS, p=0.33). Likewise, cumulative incidence of relapse at 2 years was 44%, 15% and 17% (p=0.001); however among remission patients there was no significant difference between MRD+ and MRD- patients before allo-HSCT (p=0.96). CI of NRM at 1-year was 14%, 18% and 8% for non-CR, NPM1+ CR and NPM1- CR patients (p=0.9). Intriguingly, MRD positivity as assessed per qPCR at time of transplant did not impact on post-transplant outcome in our cohort of NPM1 positive AML. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Individualised immunosuppression with intravenously administered donor-derived modified immune cells compared with standard of care in living donor kidney transplantation (TOL-2 Study): protocol for a multicentre, open-label, phase II, randomised controlled trial

IntroductionDonor-derived modified immune cells (MIC) induced long-term specific immunosuppression against the allogeneic donor in preclinical models of transplantation. In a phase I clinical trial (TOL-1 Study), MIC treatment resulted in...

Disqualification of Donor and Recipient Candidates From the Living Kidney Donation Program: Experience of a Single-Center in Germany.

BackgroundKidney transplantation is the best treatment option for patients with end-stage kidney disease (ESKD) with a superiority of graft survival after living kidney donation (LKD) compared to deceased donation. However, a large part of potential donors and recipients are ineligible for LKD. Here, we analyze the leading causes for disqualification of potential living donor-recipient pairs from the LKD program and the health-related consequences for ESKD patients excluded from the LKD program in a German transplant center.MethodsIn this single-center retrospective cohort study we evaluated all candidates (potential donors and recipients) presenting for assessment of LKD from 2012 to 2020 at our transplant center. Thereby we focused on candidates excluded from the LKD program. Main reasons for disqualification were categorized as medical (donor-related), psychosocial, immunological, recipient-related, and unknown.ResultsOverall, 601 donor-recipient pairs were referred to our transplant center for LKD assessment during the observation time. Out of those, 326 (54.2%) discontinued the program with 52 (8.7%) dropouts and 274 (45.6%) donor-recipient pairs being ineligible for LKD. Donor-related medical contraindications were the main reason for disqualification [139 out of 274 (50.7%) potential donors] followed by recipient-related contraindications [60 out of 274 (21.9%) of potential donor-recipient pairs]. Only 77 out of 257 (29.9%) potential recipients excluded from the LKD program received a kidney transplant afterward with a median waiting time of 2 (IQR: 1.0–4.0) years. Overall, 18 (7.0%) ESKD patients initially declined for LKD died in this period.ConclusionA large percentage of donor-recipient pairs are disqualified from the German LKD program, mostly due to medical reasons related to the donor and with partly severe consequences for the potential recipients. For these, alternative solutions that promptly enable kidney transplantation are essential for improving patient quality of life and survival.

Body Mass Index Thresholds and the Use of Bariatric Surgery in the Field of Kidney Transplantation in Germany

BackgroundObesity in the recipient is linked to inferior transplant outcome. Consequently, access to kidney transplantation (KT) is often restricted by body mass index (BMI) thresholds. Bariatric surgery (BS) has been established as a superior treatment for obesity compared to conservative measures, but it is unclear whether it is beneficial for patients on the waiting list.MethodsA national survey consisting of 16 questions was sent to all heads of German KT centers. Current situation of KT candidates with obesity and the status of BS were queried.ResultsCenter response rate was 100%. Obesity in KT candidates was considered an important issue (96.1%; n = 49/51) and 68.6% (n = 35/51) of departments responded to use absolute BMI thresholds for KT waiting list access with ≥ 35 kg/m2 (45.1%; n = 23/51) as the most common threshold. BS was considered an appropriate weight loss therapy (92.2%; n = 47/51), in particular before KT (88.2%; n = 45/51). Sleeve gastrectomy was the most favored procedure (77.1%; n = 37/51). Twenty-one (41.2%) departments responded to evaluate KT candidates with obesity by default but only 11 (21.6%) had experience with ≥ n = 5 transplants after BS. Concerns against BS were malabsorption of immunosuppressive therapy (39.2%; n = 20/51), perioperative morbidity (17.6%; n = 9/51), and malnutrition (13.7%; n = 7/51).ConclusionsObesity is potentially limiting access for KT. Despite commonly used BMI limits, only few German centers consider BS for obesity treatment in KT candidates by default. A national multicenter study is desired by nearly all heads of German transplant centers to prospectively assess the potentials, risks, and safety of BS in KT waitlisted patients.Graphical abstract