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26. Jahrestagung der Deutschen Transplantationsgesellschaft

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27.10.2017 - Lobby/ Posterausstellung | 12:15 - 12:45 
iCal 
Posterbegehung II

Vorsitzende


Basic Science: C. Schönemann (Berlin, DE), U. Spengler (Bonn, DE)


Immunologie: G. Einecke (Hannover, DE)


Infektiologisches Management des Transplantatempfängers: C. Boesecke (Bonn, DE), O. Witzke (Essen, DE)


Lebendspende: I. A. Hauser (Frankfurt/ Main, DE), U. Settmacher (Jena, DE)


Leber II: M. Guba (München, DE), T. Zimmermann (Mainz, DE)


Niere II: M. Fischereder (München, DE)


Psychosomatik / Ethik: S. Kröncke (Hamburg, DE), R. Viebahn (Bochum, DE)

Poster
P01
Feasibility of elbasvir/grazoprevir for treatment of chronic hepatitis C virus infection in renal transplant recipients with impaired allograft function
*Ute Eisenberger1, Justa  Friebus-Kardash 1, Hana Guberina2, Andreas Kribben1, Oliver Witzke2, Anne  Achterfeld3, Guido Gerken3, Kerstin Herzer3,4
1 Universitätsklinik Essen, Nephrologie, Essen, Deutschland
2 Universitätsklinik Essen, Infektiologie, Essen, Deutschland
3 Universitätsklinik Essen, Gastroenterologie, Essen, Deutschland
4 Universtätsklinik Essen, Abdominal- und Transplantationschirurgie, Essen, Deutschland
Abstract-Text :

Background/Aim: Direct-acing antiviral agents are highly efficient treatment options for chronic hepatitis C virus (HCV) infection after renal allograft transplantation. Treatment options for patients with impaired graft function remain limited. Therefore we assessed efficacy and safety of elbasvir/grazoprevir in chronic HCV- infected renal transplant patients with impaired allograft function.


Methods: Eleven renal allograft recipients with therapy-naïve HCV genotype (GT) 1a, 1b, or 4 were treated with the fixed dose combination of elbasvir/grazoprevir without ribavirin for 12 weeks. All recipients exhibited an impaired graft function with a glomerular filtration rate (GRF) < 60 ml /min/1.73 m² (MDRD equitation). Clinical data were retrospectively analyzed for renal and liver function parameters. Patients were closely monitored for trough levels of immunosuppressive agents, viral load, laboratory values, and potential adverse effects.


Results/Conclusion: Seven patients (64 %) exhibited a rapid virologic response within 4 weeks (HCV GT1a, n = 2; HCV GT1b, n = 5). The other four patients achieved a virologic response within 8 weeks (HCV GT1b, n =3, HCV GT 4 n =1). Results for sustained virologic response at week 12 after the end of treatment are currently pending. Clinical measures of liver function improved substantially for all patients. Adverse events were scarce (arterial hypertension (n=8), gastrointestinal symptoms (n=8), fatigue (n=6), headache (n=3)). Impaired renal allograft function and proteinuria remained stable. Importantly, dose adjustments for tacrolimus were necessary for maintaining sufficient trough levels in a majority of patients. In conclusion, the described regimen appears to be safe and effective for recipients with impaired allograft function after renal transplantation and is a promising treatment option for eradicating HCV in this patient population.



Poster
P02
Accidental transmission of Hepatitis C (HCV) virus from an organ donor to five transplant recipients: Early treatment with direct acting antivirals successfully prevents HCV-infection
*Michael Dürr1, Klemens Budde1, Jörg Hofmann2, Ute Eisenberger3, Kerstin Herzer4, Martina Sterneck5, Jens Gottlieb6, Uwe Schulz7, Fabian Halleck1
1 Charité Universitätsmedizin Berlin, Medizinische Klinik m. S. Nephrologie und Intensivmedizin, Berlin, Deutschland
2 Charité Universitätsmedizin and Labor Berlin Charité-Vivantes GmbH, Institut für Virologie, Berlin, Deutschland
3 Universitätsklinikum Essen-Duisburg, Klinik für Nephrologie, Essen, Deutschland
4 Universitätsklinikum Essen-Duisburg, Klinik für Gastroenterologie und Hepatologie, Essen, Deutschland
5 Universitätsklinikum Hamburg-Eppendorf, Medizinische Klinik, Hamburg, Deutschland
6 Medizinische Hochschule Hannover, Klinik für Pneumologie, Hannover, Deutschland
7 Klinik für Thorax- und Kardiovaskularchirurgie, Herz- und Diabeteszentrum Nordrhein-Westfalen, Bad Oeynhausen, Deutschland
Abstract-Text :

Background: Limited data exist analyzing transmission rates of Hepatitis C virus (HCV) and time course of HCV infection after solid organ transplantation. No data exist on the efficacy and outcome of an early-initiated treatment course with new direct acting antivirals (DAAs) directly after confirmed HCV transmission.


Methods: Clinical information of the HCV-positive organ donor and five recipients in five different transplant centers after accidental HCV transmission were collected. Sera from all recipients and the donor were tested for serologic and nucleic acid tests (NAT) of HCV infection before and 16 weeks post-transplant.


Results: The organ donor was a 55 years old woman who died due to subarachnoid hemorrhage. The donor did not belong to a HCV high-risk group. On day 4 of ICU stay donor received one unit of packed red blood cells. Routine serological testing for anti-HCV IgG at time of donation was negative. NAT for HCV was initially not performed.


All 5 transplant recipients were tested negative for anti-HCV IgG and had negative HCV-NAT before transplantation. All patients had detectable quantitative (q) HCV-NAT early post-transplant. Retrospective analysis revealed that the organ donor had low level HCV-RNA (17,700cop;genotype 1a) in the blood.


In 4 patients, a 12 weeks course of different DAA regimens was initiated after a median of 9.5 days with early viral response (EVR) at treatment week 4. The liver recipient had multiple postoperative complications and died due to septic shock. All other recipients had good graft function 16 weeks post-transplant and achieved a sustained virological response 4 weeks after end of therapy (SVR4).


Conclusion: HCV has a high transmission rate in solid organ transplantation with early active replication onset in the recipient. Early initiation of therapy with DAAs seems to effectively prevent chronic HCV infection.



Poster
P03
Immune monitoring-guided treatment of a pediatric patient with sequential GvHD, acute rejection and CMV infection following lung transplantation
*Christine Falk1,2, Nicolaus Schwerk3, Carsten Müller3, Igor Tudorache4, Wiebke Sommer4, Kerstin Daemen1, Jana Keil1, Gesine Hansen3, Axel Haverich4, Gregor  Warnecke4
1 Medizinische Hochschule Hannover, Institut für Transplantationsimmunologie, Hannover, Deutschland
2 DZIF, TTU-IICH SP3, Hannover, Deutschland
3 MHH, Abteilung Pädiatrische Pneumologogie, Hannover, Deutschland
4 MHH, Abteilung für Herz-, Thorax- Transplantations- und Gefäßchirurgie, Hannover, Deutschland
Abstract-Text :

Background: A 17 year old patient with cystic fibrosis (HLA-A11 ,CMV-) underwent bilateral sequential lung transplantation (donor: HLA-A32 ,CMV ). Immunosuppression (IS) consisted of Tacrolimus, MMF and Prednisone. After uneventful 3 months, he developed histology-proven cutaneous GvHD treated successfully by withdrawal of MMF. He developed acute rejection treated by a steroid pulse. While lung function returned to normal, he developed CMV infection despite valganciclovir prophylaxis.


Methods: Frequencies of HLA-A32 donor lymphocytes were measured by FACS. ELISpots were performed to detect allospecific (rejection vs. GVHD) and CMV-specific T cells. HLA-A2/NLV-pentamer staining was used for CMV-specific CD8 CTL. Plasma cytokines were measured by multiplex assays.


Results: With development of skin GvHD, frequencies of 4% HLA-A32 donor CD4 ,CD8 T cells, 5-8% B cells and 1-4% NK cells were detected for 2 weeks. Donor T, NK cells declined after MMF withdrawal, B cell frequencies remained stable. Simultaneously to improvement of GVHD, acute rejection developed, accompanied by significantly increased allo-A32-specific CD8 T cells, which declined upon steroid pulse. Allo-HLA-A11-restricted T cells were found at low frequencies. Steroid pulse was accompanied by serological detection of CMV which induced HLA-A2/NLV specific CD8 T cells producing IFN-g. CMV viremia disappeared with the emergence of CMV-specific CTL. Plasma levels of sCD25, IFN-g responded to IS alterations, to pulsed steroids with a transient drop.


Conclusions: Using specific immune monitoring tools, we could confirm clinical diagnoses of the patient. Frequencies of allo- or virus specific T cells, donor lymphocytes and plasma cytokine levels followed the clinical course of GVHD, followed by rejection followed by CMV infection. The modification of IS by using immune monitoring information resulted in a full recovery of the patient who is still asymptomatic several months after these complications.



Poster
P04
Invasive zerebrale Aspergillose nach Nierentransplantation
*Sarah Rudolf1, Stefan Büttner1, Julian Gebhardt1, Nicholas Obermüller1, Helmut Geiger1, Ingeborg A. Hauser1
1 Universitätsklinikum Frankfurt, Medizinische Klinik III - Nephrologie, Frankfurt am Main, Deutschland
Abstract-Text :

Hintergrund: Eine Aspergillusinfektion nach NTx ist ein seltenes, aber lebensbedrohliches Ereignis. Eine ZNS-Beteiligung erschwert die Therapie, die Letalität ist insbesondere unter immunsuppression (IS) erhöht.


Case-Report: Ein seit 5 Jahren transplantierter 58-jähriger Mann stellte sich mit Cephalgien, Oberlidschwellung, Visusverlust und Ptosis, sowie Dysphagie und Hypakusis vor. Das cCT zeigte eine Orbitaraumforderung mit knöcherner Destruktion Richtung Temporallappen, die histologisch einer chronischen granulomatösen Sinusitis mit schwerster florider und nekrotisierender Entzündung entsprach. Nach kulturellem Nachweis von Aspergillus fumigatus wurde eine antimykotische Therapie mit Posaconazol begonnen und die IS reduziert (MMF Pause, Tac-Zielspiegel<3ng/ml, Steroid 5mg/d). Trotz Therapie und operativer Fokussanierung im HNO-Trakt und nach Umstellung auf das besser liquorgängige Voriconazol kam es nach fast einjähriger Therapie zur progredienten Infiltration in den Temporallappen sowie entlang der Schädelbasis mit Affektion der Nn. facialis und abducens. Es erfolgte die Eskalation um Ambisome und Anidulafungin, sowie die Umstellung der IS auf niedrig dosiertes CsA. Aufgrund fehlender Regression und systemischer NW (PNP, Leberwerterhöhungen), erfolgte erneut ein Umstellung auf Isavuconazol und Prednison-Monotherapie. Hierrunter zeigte sich erstmals ein regredientes Aspergillom und eine Besserung der neurologischen Symptomatik. Jedoch traten im Verlauf donorspezifische AK und eine progrediente Transplantatverschlechterung auf,  die schließlich im chronischen Transplantatversagen mündeten.


Schlußfolgerung: Eine frühzeitige Diagnosestellung und Therapie ist bei Aspergillusinfektionen nach NTx essentiell um das Überleben zu verbessern. Die Therapie ist komplex und langwierig, und kann trotz Reduktion der IS und mehrmonatiger Therapie, unter Inkaufnahme eines Transplantatversagens, zum Absetzen der IS zwingen.



Poster
P05
Safety of DAA therapy regarding renal function in post-liver transplant patients infected with hepatitis c and a 100% SVR12 rate - a single center study
*Georg Peschel1, Kilian Weigand1, Marcus N Scherer2, Martina Müller1
1 Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin I, Regensburg, Deutschland
2 Universitätsklinikum Regensburg, Chirurgie, Regensburg, Deutschland
Abstract-Text :

Direct acting antiviral (DAA) therapy of hepatitis c virus (HCV) infection is well established in patients with and without cirrhosis of the liver. Patients after liver transplantation with ongoing HCV infection often suffer from renal and hepatic impairment. A major concern when treating HCV patients after liver transplantation is the potential interaction of DAA and immunosuppressive therapy that might result in decreasing renal function. In this single centre study we analysed clinical parameters of 18 HCV infected patients treated with DAA therapy after liver transplantation. The primary endpoints were change of renal function (GFR) and viral eradication 12 weeks after therapy (SVR 12). For secondary endpoints we investigated the influence of DAA therapy over time on transaminases, bilirubin, INR, non-invasive fibrosis measurement and MELD Score. 5 out of 18 patients treated with DAA suffered from renal impairment stage 2 and 7 out of 18 patients of renal impairment stage 3. Renal function at SVR 12 was neither influenced whether there was pre-existing renal impairment (p >0,5), nor by the type of immunosuppressant (p >0,5), nor the type of DAA regime (p >0,5). All patients reached SVR12 regardless to their genotype or the type of DAA regime. In respect of secondary endpoints the type of immunosuppressant had no influence on renal function or SVR12 rate. The levels of transaminases and bilirubin declined rapidly as expected. 10 out of 18 patients already suffered from cirrhosis or liver fibrosis greater than F3 in non-invasive measurement before initiation of treatment. Even in this short period of time single point acoustic radiation force impulse imaging (ARFI) improved in 9 patients (p=0,012). In conclusion, DAA-therapy in liver transplant patients was effective and safe in this single centre real life cohort. Renal function was not influenced by the administered drug combinations, even in patients with pre-existing renal impairment.



Poster
P18
The choice of renal replacement therapy (CORETH) project: Patient participation, quality of life and economic consequences
*Carina Oedingen1, Denise Neumann2, Wilfried Mau2, Matthias Girndt3, Christian Krauth1
1 Medizinische Hochschule Hannover, Institut für Epidemiologie, Sozialmedizin und Gesundheitssystemforschung, Hannover, Deutschland
2 Medizinische Fakultät der Martin-Luther-Universität Halle-Wittenberg, Institut für Rehabilitationsmedizin, Halle (Saale), Deutschland
3 Martin-Luther-Universität Halle-Wittenberg, Universitätsklinik und Poliklinik für Innere Medizin II, Halle (Saale), Deutschland
Abstract-Text :

Introduction and Background: For end-stage renal disease as a technical substitute of the organ function, treatment is often either done by centre haemodialysis (HD) or by peritoneal dialysis (PD). Although both dialysis procedures are resource consuming, a comprehensive cost finding is still lacking in Germany. The aim of the CORETH project is to compare the direct medical and non-medical as well as the indirect costs between HD and PD.


Methods: From 55 nationwide dialysis centers, a total of 780 patients have been surveyed with standardised questionnaires. Information was collected about services at doctor visits, hospitalisations, medications, medical treatments, rehabilitations, transportations and inabilities to work. To compare patients of the HD and PD with regard to relevant covariates, a propensity score (PS) matching at the individual level with a 1:1 matched ratio was conducted. The PS model is estimated by a logistic regression. The cost analysis from the perspective of the statuary health insurance as well as the social perspective of the HD and PD can examine the effect of other determinants on the costs.


Results and Conclusion: 780 patients received either HD (n=529) or PD (n=251). The cohort differed significantly concerning age, gender, education, employment status, net equivalent household income, comorbidities (Charlson Comorbidity Index) and social support. These differences were balanced after PS matching so that 188 matched pairs of HD- and PD-patients were identified. Because the standardised mean differences were ≤10%, the PS matching has achieved a suitable balance between patients of HD and PD (more results to follow). A PS matching for different patients of HD and PD provide a basis for further cost analysis. For a complete contemplation of the costs between HD and PD, unmatched cases should be also analysed.



Poster
P19
PPARgamma as a putative stress marker in T cells following kidney transplantation
Ramin Aghajaanpour1, Marco Brenneis1, Nadine Köhler2, Tilo Knape3, Stefan Büttner2, Laura Kuchler1, Michael J. Parnham3, Bernhard Brüne1, Ingeborg A. Hauser2, *Andreas von Knethen1
1 Goethe-Universität Frankfurt/Main, Institut für Biochemie I, Frankfurt/Main, Deutschland
2 Goethe-Universität Frankfurt/Main, Medizinische Klinik III, Abteilung für Nephrologie, Frankfurt/Main, Deutschland
3 Fraunhofer Institut für Molekularbiologie und angewandte Ökologie - IME, Projektgruppe Translationale Medizin und Pharmakologie TMP, Frankfurt, Deutschland
Abstract-Text :

Introduction and Background: The identification of biomarkers is important to allow prognosis of diseases and an appropriate therapeutic regimen. Based on our previous findings, characterizing PPARgamma expression in T cells derived from blood of sepsis patients as a marker of disease progression, we were interested to determine whether PPARgamma expression in T cells is altered in dialysis patients or following kidney transplantation (KTX).


Methods: Blood samples of patients one day before and up to 90 days after KTX were drawn. We determined the leukocyte count and the number of CD3 T cells per ml blood by FACS analysis. PPARgamma mRNA expression in MACS enriched CD3 T cells was performed by qPCR.


Results and Conclusions: Under immunosuppressive treatment following KTX, we observed a significant decrease of CD3 T cells in all patients compared to healthy controls. Subpopulations of CD3 T cells, i.e. CD4 and CD8 T cells, were similarly affected. Interestingly, in transplant patients there were two subgroups; one showed upregulated PPARgamma expression in T cells (> 2000 copies/25 ng RNA), whereas in the second group PPARgamma expression remained low (< 2000 copies/25 ng RNA). Considering co-morbidities of the allograft recipients, we observed that PPARgamma mRNA expression was high in patients suffering from an acute or chronic infection. Focusing on the role of dialysis, in T cells derived from patients who had not been dialysed after KTX, PPARgamma expression was low, whereas dialysis treatment increased T cell PPARgamma. Most likely the reduced count of CD3 cells can be attributed to immunosuppression during anti-thymoglobulin treatment, steroids or calcineurin inhibitors. Acute biopsy-confirmed rejection episodes did not occur in our patients. In conclusion, our preliminary study suggests that PPARgamma mRNA expression may be used as a marker for activation of T cells due to infection(s) or reperfusion injury.



Poster
P20
Impaired outcome of kidney transplants from donors with acute kidney injury
*Katharina Schütte-Nütgen1, Sabrina Ehlert1, Gerold Thölking1, Hermann Pavenstädt1, Barbara Suwelack1, Daniel Palmes2, Ralf Bahde2, Stefan Reuter1
1 Universitätsklinikum Münster, Medizinische Klinik D, Münster, Deutschland
2 Universiätsklinikum Münster, Klinik für Allgemein- und Viszeralchirurgie, Münster, Deutschland
Abstract-Text :

Given the gap between patients in need of a renal transplantation (RTx) and organs available, transplantation centers increasingly accept lower quality organs, e.g. from donors with acute kidney injury.


To determine the outcome of kidney transplants from deceased donors with acute kidney injury (AKI, defined as ≥ AKIN stage 1), all 109 kidney transplant recipients who received a renal allograft from donors with AKI between August 2004 and July 2014 at our center were compared to their respective consecutively transplanted patients receiving kidneys from donors without AKI. Patient and graft survival at 5 years after RTx, frequencies of delayed graft function (DGF, need for dialysis < 1 week post RTx) and biopsy-proven acute rejections (BPAR) within the first year after RTx as well as estimated glomerular filtration rate (eGFR, CKD-EPI) were assessed.


5-year patient survival was similar between recipients of kidneys from donors with and without AKI (p=0.128), whereas 5-year death-censored graft survival and overall graft survival were decreased in recipients of AKI kidneys (97.2 % vs. 90.7 %, p=0.028 and 91.6 % vs. 80.4 %, p=0.011, respectively). Recipients of AKI kidneys showed higher frequencies of DGF (p=0.0015) and had a reduced eGFR at 7, 90 and 365 days after RTx (p=0.002, 0.001 and 0.003, respectively). Prevalence of patients who had one or more BPAR episodes within the first year after RTx was similar in both groups (p=0.872).


In our cohort, both short-term and long-term outcome was impaired in patients with kidney allografts from donors with AKI, while other groups report higher rates of DGF in recipients of AKI kidneys, but similar long term outcome. Our data indicates that additional factors impairing long term outcome, e.g. cold ischemia time, should be minimized with particular precaution once kidneys from donors with AKI are considered for transplantation.  



Poster
P21
Delayed graft function is associated with an increased rate of renal allograft rejection: A retrospective single center analysis
Thomas Dienemann1, Susanne Weber1, Johannes Jacobi1, Kai-Uwe Eckardt1,2, *Alexander Weidemann3,1
1 Universität Erlangen-Nürnberg, Medizinische Klinik 4 - Nephrologie und Hypertensiologie, Erlangen, Deutschland
2 Charite - Universitätsmedizin Berlin, Nephrologie und internistische Intensivmedizin, Berlin, Deutschland
3 Kliniken Köln, Krankenhaus Merheim, Nephrologie, Transplantation und internistische Intensivmedizin, Köln, Deutschland
Abstract-Text :

Introduction: The association of delayed graft function (DGF) and biopsy proven acute rejection (BPAR) of renal allografts is controversial. Borderline rejections (BR) comprise a major portion of biopsy results but the significance of such histologic changes is debated. The present study explores the impact of DGF on BPAR with a special emphasis on discriminating the effects of BR.


Methods: Single center analysis of 417 deceased donor kidney recipients (age>18; transplantation date 1/2008 – 2/2015). Patients with primary non-function were excluded. DGF was defined as the need for dialysis within the first week after transplantation. Acute rejection was defined according to Banff criteria. Cox proportional hazards models were used to examine the relationship of DGF with BPAR within the first year.


Results: No graft loss was observed during the first year after transplantation. DGF significantly associated with BPAR in the first year, irrespective of whether BR was included (HR 1.63, 95% CI 1.12,2.39) or excluded (HR 1.67, 95% CI 1.08,2.62).


Conclusion: DGF is significantly associated with rejection - with or without borderline changes - within the first year.



Poster
P22
SGLT2 inhibition in kidney transplant recipients with diabetes
*Martina Guthoff1, Moritz Mahling1, Silvio Nadalin2, Nils Heyne1
1 Medizinische Klinik IV, Sektion Nieren- und Hochdruckkrankheiten, Tübingen, Deutschland
2 Universitätsklinik für Allgemeine, Viszeral- und Transplantationschirurgie, , Tübingen, Deutschland
Abstract-Text :

Purpose: Sodium-glucose cotransporter 2 (SGLT2) inhibition has been shown to reduce cardiovascular mortality and preserve kidney function in patients with type 2 diabetes. Kidney transplant recipients with diabetes demonstrate increased risk and accelerated progression of micro- and macrovascular complications. However, potential concerns of SGLT2 inhibition include volume depletion and acute kidney injury as well as urinary tract infections. Here we report safe application of SGLT2 inhibitors in an ongoing case series of patients after kidney transplantation.


Methods: Kidney transplant recipients started on empagliflozin for better glucose control were included in the analysis. Patients with a stable allograft function (eGFR ≥ 45 ml/min/1.73m²) were eligible for SGLT2 inhibition. Empagliflozin was given as add-on to preexisting antidiabetic treatment with dose reduction of the latter. Patients were asked to ensure adequate hydration and urogenital hygiene.


Results: To date, 4 patients have entered the analysis. Median eGFR at baseline was 75 ml/min/1.73m² with a median time since transplantation of 8,7 yrs. Median HbA1c prior to treatment was 7.6%, median fasting plasma glucose 168 mg/dl. During follow-up, kidney allograft function remained stable in all patients. No side effects were reported. Required insulin doses decreased by 27% and HbA1c could be markedly improved. Updated results from the ongoing analysis will be presented.


Conclusions: SGLT2 inhibition is safe in selected kidney transplant recipients with diabetes. Glucose control can be improved despite reduction in concomitant antidiabetic treatment. Whether SGLT2 inhibition is able to reduce cardiovascular mortality and improve allograft survival in these patients has to be addressed in further studies.



Poster
P23
Autotransplantation der Niere: Ein Schritt in die Zukunft durch eine längst vergessene Technik?
*Karl Weigand1, Nasredin Mohammed1, Felix Kawan1, Andre Schumann1, Paolo Fornara1
1 Martin-Luther-Universität Halle, Klinik und Poliklinik für Urologie mit Nierentransplantationszentrum, Halle, Deutschland
Abstract-Text :

Einleitung: Die erste Nieren-Autotransplantation wurde 1963 von J. D. Hardy in Minnesota bei einer Ureterläsion durchgeführt. Heute existieren eine Vielzahl an komplexen Krankheiten wie iatrogene Ureterverletzungen, Steinleiden, Nierenschmerz-Syndrom, Autoimmunerkrankungen oder renovaskuläre Erkrankungen wie Stenosen der distalen Nierenarterien, intrarenale Aneurysmen, arteriovenöse Fehlbildungen und signifikante Mehrgefäßkrankheiten für eine Autotransplantation.


Methode: Zwischen 2001 und 2015 wurden an unserer Klinik 8 Nieren- Autotransplantationen durchgeführt. Demographische, klinische und Labordaten der Patienten wurden in der prä-, intra- und postoperativen Phase gesammelt und analysiert.  7 Pat. wurden offen,1 Pat. robotisch operiert.


Ergebnisse: Das mittlere Patientenalter lag bei 45,8Jahre (26-60 Jahre), alle waren männlich und hatten einen durchschnittlichen BMI von 27,9kg/m2 KO (20,8 – 37,5 kg/m2 KO). Die seitengetrennte Nierensequenzszintigraphie war durchschnittlich 51,4 % (39-87 %) für die betroffene Seite. Die Gefäßversorgung von 7 Patienten war ein stämmig, lediglich 1 Patient zeigte eine Variation mit vier Arterien und zwei Venen. Die mittlere Operationsdauer betrug 246min. (174–335 min). Die Durchschnittliche warme Ischämiezeit betrug 107,5 sec. (45–175 sec.), die durchschnittliche kalte Ischämiezeit betrug 41,7 min. (38–45 min.) und die durchschnittliche handling-time 52,7 min. (32–90 min.). Bei 2 Patienten zeigten sich Komplikationen im Grad 2-3b nach der CDC. Die Retentionswerte waren im Vergleich präoperativ zu dem Entlassungszeitpunkt stabil, es gab keinen Einfluß auf den Blutdruck oder die antihypertensive Medikation.


Schlußfolgerung: Unter strenger Indikationsstellung ist die Nieren-Autotransplantation ein sicheres und effektives Verfahren zum Erhalt der Nierenfunktion setzt aber eine außerordentliche Expertise im Bereich der Organentnahme, der Organkonservierung, der Transplantation und des postoperativen Management voraus.



Poster
P24
Identifizierung eines Transplantatnierenempfängers mit ultraschneller Metabolisierung von Tacrolimus und personalisierte Therapieanpassung
*Alexander Holderied1, John Hoppe1, Markus Schwarz1, Veronika Srna1, Ulf Schönermarck1, Antje Habicht1, Michael Fischereder1
1 Klinikum der Universität München, , München, Deutschland
Abstract-Text :

Die "area-under-the-concentration-over-time" Kurve (AUC (0-24h)) stellt die optimale Methode der Dosisüberwachung der Therapie mit Calcineurin-Inhibitioren dar. In der Praxis erfolgt die Dosisüberwachung aus praktischen Gründen und wegen der (in der Regel) guten Korrelation mit der AUC (0-24h) jedoch durch Bestimmung des Talspiegels. Eine weitere Methode zur Dosisanpassung stellt die "blood concentration normalized by the daily dose" (C/D) Ratio dar. Diese Methoden wurden weitgehend anhand von Patienten mit normaler (schneller) Pharmakokinetik etabliert. Passt man z.B. die Dosierung anhand des Talspiegels an, so benötigen sog. "ultraschnelle Metabolisierer" jedoch eine höhere Einzeldosis um den gleichen Talspiegel zu erreichen. Daher sind diese Patienten gefährdet eine höhere AUC (0-24h) und durch die stärkere Immunsuppression häufiger Nebenwirkungen zu entwickeln.


Wir berichten von einem afrikanischen Transplantatnierenempfänger, der sich mit abdominellen Schmerzen und Ulzera der Kolonschleimhaut als Nebenwirkung seiner Therapie mit Tacrolimus (Envarsus®) vorstellte. Er hatte eine hohe C/D Ratio (0,25 ng/ml*1/mg) bei einem Tacrolimus Talspiegel von 3,8 ng/ml (Referenzwert: 6-10 ng/ml). Seine Tacrolimus AUC (0-24h) zeigte mit 379 ng/ml eine Über-Immunsuppression. Damit einhergehend war seine Halbwertszeit für Tacrolimus bei einem hohen Spitzenspiegel und einem niedrigen Talspiegel deutlich verkürzt, was eine "ultraschnelle" Metabolisierung vermuten ließ. Die genetische Untersuchung bestätigte eine Homozygotie für zwei CYP3A5 Allele, welche eine hohe Enzymaktivität verursacht und mit einer "ultraschnellen" Metabolisierung von Tacrolimus einhergeht. Eine Änderung der Applikationshäufigkeit von Envarsus® konnte bei einer angepassten AUC (0-24h) die Nebenwirkungen der Therapie reduzieren.


In diesem Fallbericht schlagen wir einen diagnostischen Algorithmus vor, um "ultraschnelle Metabolisierer" zu identifizieren und eine personalisierte Therapie zu ermöglichen.



Poster
P49
Modelling the protein quality control of transthyretin in hepatocyte-like cells
*Christoph Niemietz1, Lutz Fleischhauer1, Vanessa Sauer1, Sarah Guttmann1, Sara Reinartz Groba1, Paula Ballmaier1, Andree Zibert1, Hartmut H.-J. Schmidt1
1 Universitätsklinikum Münster, Klinik für Transplantationsmedizin, Münster, Deutschland
Abstract-Text :

Introduction and Background


Transthyretin-related hereditary amyloidosis (ATTR) is caused by mutations of transthyretin (TTR), primarily expressed by the liver. A competition between ER-assisted folding (ERAF) and degradation (ERAD) of TTR seems to be an important parameter of the disease. We took advantage of induced pluripotent stem cell-derived (iPSC) hepatocyte-like cells (HLCs) to study whether pathogenic mechanisms of ATTR are linked to the protein quality control (PQC).


Methods


Urine from ATTR patients (n=5) and healthy individuals (n=4) was processed for isolation of renal epithelial cells, followed by reprogramming into iPSCs and differentiation towards hepatocytes. The hepatic character of HLCs was assessed by functional analyses, gene expression profiling and immunostainings. qPCR was used to analyse gene expression. Protein expression was determined by western blot and ELISA.


Results and Conclusions


HLCs derived from ATTR patients carrying three different mutations of TTR showed high expression of hepatic markers, especially TTR. 39 genes related to PQC were analysed in HLCs, with 32 genes coding for chaperones predominantly located intracellular and 7 located extracellular. Expression of extracellular chaperones was identified to be differently regulated in ATTR patients. SERPINA1 expression was identified to be differently expressed in ATTR and healthy donor HLCs post-TTR downregulation suggesting a regulated expression of variant forms of TTR. Our data show that HLCs derived from ATTR patients are an excellent model to study patient-specific disease mechanisms in the genuine genetic background. Identification of PQC genes involved in chaperoning of variant TTR, e.g. SERPINA1, might illume amyloidogenic pathways and pave the way to new therapy approaches.



Poster
P50
Efficacy and safety of everolimus (EVR) with reduced exposure tacrolimus or cyclosporine in pediatric liver transplantation recipients (pLTxR): 24-month results from H2305-Study (NCT01598987)
*Rainer Ganschow1, Bo-Göran Ericzon2, Anil Dhawan3, Khalid Sharif4, El-Djouher Martzloff5, Barbara Rauer5, Jennifer Ng6, Patricia M Lopez5
1 Universitaetsklinikum Bonn, Klinik und Poliklinik für Kinderheilkunde, Bonn, Deutschland
2 Karolinska University Hospital Huddinge, , Stockholm, Schweden
3 Kings College Hospital, , London, Vereinigtes Königreich
4 Birmingham Childrens Hospital, , Birmingham, Vereinigtes Königreich
5 Novartis Pharma AG, , Basel, Schweiz
6 Novartis Pharmaceutical Corporation, , East Hanover, Vereinigte Staaten
Abstract-Text :

Introduction: EVR with reduced tacrolimus (rTAC) provides anti-rejection efficacy and preserves renal function (RF) in adult LTx, yet data on EVR use pLTxR are limited. Here we present efficacy, RF and safety of EVR rTAC/reduced cyclosporine (rCsA) in pLTxR.


Methods: In this 24M, multicenter, open-label, single-arm, prospective study, pLTxR (≥1M and <18y) treated with CsA/TAC±mycophenolate±steroids were enrolled from M1 to M6 post Tx. Primary objective was evaluation of RF (eGFR; Schwartz formula) from EVR start to M12. Based on data monitoring committee recommendation, recruitment was prematurely stopped due to increased risk of PTLD, serious infections in patients <7y.


Results: Of 56 patients, 25 were <2y and 31 were 2-<18y. Mean age was 4.9y at BL. EVR and CsA (n=6) or TAC (n=50) C0 were within target ranges up to M24 for most patients. Mean and median EVR C0 were higher in <2y vs 2-<18y patients. Mean TAC C0 was near the upper end of target range up to M6. Same trend was observed for CsA C0 from week 1 to M3. Mean observed eGFR at BL, M12 and M24 was 90.5(22.2), 96.7(17.8) and 92.2(14.9) mL/min/1.73m², respectively. Mean eGFR increased by 6.2 and 4.5 mL/min/1.73m² from BL to M12 and M24, respectively. M24 data is based on 36% of patients compared to BL. 2 tBPAR episodes were reported but no graft loss or death. PTLD was reported in 6(10.7%) patients, 3 each in <2y and 2-<18y (1 case reported 1y post study completion). No negative effect on growth or sexual development was noted.


Conclusion: Despite good RF, the study outcomes suggest overimmunosuppression, as evident by low tBPAR, high rates of PTLD and serious infections. However, evidence is limited due to premature termination of recruitment and high rate of treatment discontinuation.



Poster
P51
The "weekend effect" in liver transplantation - A retrospective single centre study
*Felix Becker1, Thekla Voß1, Anne-Sophie Mehdorn 1, Katharina Schütte-Nütgen 2, Stefan Reuter 2, Iyad Kabar3, Thorsten  Vowinkel1, Norbert Senninger1, Daniel  Palmes1, Thomas Vogel1, Ralf Bahde1, Linus  Kebschull1
1 Universitätsklinikum Münster, Allgemein- und Viszeralchirurgie, Münster, Deutschland
2 Universitätsklinikum Münster, Medizinische Klinik D, Münster, Deutschland
3 Universitätsklinikum Münster, Klinik für Transplantationsmedizin, Münster, Deutschland
Abstract-Text :

Introduction The "weekend effect" describes a phenomenon whereby patients admitted to hospitals on weekends are at higher risk of complications, worse outcome and death compared to those admitted during weekdays. However, it remains unknown if the "weekend effect" applies to liver transplantation (LT).


Methods: We retrospectively analyzed data from 326 LT Patients between January 2006 and May 2016 and grouped patients based on time of LT (Saturday, Sunday vs. weekday). We assessed one-year patient and graft survival, biopsy proven acute rejections (AR), primary non-function (PNF), surgical complications requiring re-operation, length of stay and number and length of re-admissions.


Results and Conclusions: We identified 243 patients (74.5%) with an LT performed during the week and 83 (25.5%) receiving LT on the weekend. Potential confounders such as age, gender, indication for LT, cold and warm ischaemia time, MELD score and number of high-urgency LTs were all similar between the two groups. One-year patient survival (74.1% vs. 72.3%, p=0.665) as well as graft survival (71.6% vs. 66.3%, p=0.307) were similar between weekday and weekend LT. Frequencies of AR (14.4% vs. 19.3%, p=0.297) and PNF (7.8% vs. 12.0%, p=0.266) were also not different between weekday and weekend LT. The rate of complications requiring re-operation was 57.6% for weekday and 57.8% for weekend LT (p=1), with re-transplantation frequencies of 9.1% and 10.8% (p=0.666), respectively. The initial hospital stay was marginally longer for weekday patients (39d vs. 30d, p=0.051). In conclusion, the findings suggest that there was no "weekend effect" regarding outcomes after LT at our centre. While the "weekend effect" has been described for various time-sensitive acute conditions and emergencies such as acute myocardial infarction, the absence of the "weekend effect" in LT could be due to highly specialised teams and standardised workflows in transplant medicine.



Poster
P52
Impact of immortalization for establishment of hepatocyte-like cells
*Paula Ballmaier1, Christoph Niemietz1, Sarah Guttmann1, Sara Reinartz Groba1, Vanessa Sauer1, Andree Zibert1, Hartmut H.-J. Schmidt1
1 Universitätsklinikum Münster, Klinik für Transplantationsmedizin, Münster, Deutschland
Abstract-Text :

Introduction and Background: Hepatocyte-like cells (HLC) generated from induced pluripotent stem cells (iPSC) offer great opportunities to study diseases in a patient-specific manner. Urine-derived cells (UCs) are an easy attainable source of primary cells and can be used for the generation of iPSC. Unfortunately, like primary hepatocytes, HLC do not proliferate in vitro and consecutive differentiations are time consuming. The use of genes reported to immortalize cells could boost the current protocols of HLC generation. We wanted to investigate whether transfer of genes mediating immortalization modulates the process of reprogramming and differentiation.


Methods: Retroviral transduction using various gene combinations was performed at different stages of reprogramming and differentiation. Cells were transduced with hTERT/p53, CyclinD1/CDK4, and HPVE6E7 or combinations thereof. The influence of gene transfer was assessed by determination of cell proliferation, mRNA expression (qRT-PCR) and protein expression (e.g. flow cytometry, immunofluorescence).


Results and Conclusions: Untreated or GFP transduced UCs underwent senescence after 5-10 days. In contrast, UCs could be cultured for several months in the presence of HPVE6E7 (UCim; n=3). Expression of renal, epithelial and fibroblast marker genes in UCs and UCim was in the same range. Using a transient, EBV-based expression system for reprogramming, UCim could be reprogrammed to iPS cells that expressed typical markers of pluripotency. However, reprogramming of UCim resulted in less iPSC-like colonies (iPSCim) and was delayed. The expression of hepatic markers was assessed after hepatic differentiation of UCim (HLCim). Expression of transgenes was downregulated after reprogramming to iPSCim and differentiation to HLCim.



Poster
P53
Outcome following right-extended split liver transplantation in the recent transplant era – Single center analysis
*Uta Herden1, Lutz  Fischer1, Björn  Nashan1
1 University Medical Center Hamburg-Eppendorf, Department of Hepatobiliary and Transplant Surgery, Hamburg, Deutschland
Abstract-Text :

Background: In case of allocation of the graft to a small child classic liver graft splitting is performed with consecutive transplantation of the right-extended liver in an adult. Based on organ quality data a clearly superior outcome following split liver transplantation (LTX) should be expected, especially in contrast to the decreasing donor quality in Europe since implementation of the MELD allocation system.


Methods: We analysed our recipients of right-extended grafts regarding donor/recipient data and outcome (2007-2015). Special regard was given to the splitting procedure (in-house liver graft splitting by the own team versus external liver graft splitting by a different team with subsequent graft shipping).


Results: We found excellent donor data with hemodynamic stable donors (short ICU stay (3±3 days), low maximum catecholamine level (0.2±0.2 μg/kg/min), low reanimation rate (23%)) of a young age (28±13 y) with normal or at most slightly elevated liver enzymes. Recipient characteristics were comparable between patients with in-house versus external liver graft splitting, however cold ischemic time was significant longer in external liver graft splitting (14±2 versus 12±2 hours). Interestingly, there was a significant reduced patient and a clear trend to a reduced graft survival with external liver graft splitting. Likewise the rate of biliary and vascular complications was higher in patients with external versus in-house liver graft splitting (21% and 12% versus 8% and 0%).


Conclusion: In our study we found a negative impact of external liver graft splitting on the outcome and surgical complications. This may related to the prolonged cold ischemic time due to twofold transportation and the ignorance of the detailed splitting procedure and pitfalls.



Poster
P54
How do mTor inhibitors modulate HCV replication activity: an approach by whole genome analysis
*Alexandra Frey1, Andreas Walker1,2, Martin Trippler1, Guido Gerken1, Kerstin Herzer1,3
1 University Hospital Essen, Clinic for Gastroenterology and Hepatology, Essen, Deutschland
2 University Hospital Düsseldorf, Institute of Virology, Düsseldorf, Deutschland
3 University Hospital Essen, Clinic for General, Visceral and Transplant Surgery, Essen, Deutschland
Abstract-Text :

Introduction and background: Hepatitis C virus (HCV) infection remains an important cause for liver transplantation (LT) and reinfection of the liver graft is a serious challenge. The influence of mTor inhibitors as immunosuppression (IS) after LT on HCV replication activity and, thus, reinfection of the graft, has not been elucidated so far. We could previously show that mTor inhibitors (everolimus (EVR), sirolimus (SRL)) exert genotype (GT)-dependent effects on HCV replication activity. Aim of this study is to investigate the molecular background of this differential effect.


Methods: GT1b (Con1) and GT2a (Huh7.5 JFH/SG-Feo) replicon cells were treated with mTor inhibitors and the gene expression profile was generated using GeneChip® Human Transcriptome Array 2.0. Those genes, which showed a differential regulation between HCV genotypes, were further analyzed by qRT-PCR.


Results and conclusions: As genes of interest were those selected which were previously described in the context of viral hepatitis: cyclin T1 (CCNT1), the transcription factor E2F2 and the hepatitis A virus cellular receptor 1 (HAVCR1). Treatment of GT2a cells with either mTor inhibitor resulted in 1.5-fold higher CCNT1 expression (EVR: P≤0.005, SRL: P≤0.05) and 2-fold increase in E2F2 expression (EVR / SRL: P≤0.05) compared to the untreated control while there was no change in expression of these two genes in GT1b cells. HAVCR1 was reduced by 0.5-fold in the GT1b cells by EVR or SRL treatment (EVR: P≤0.005, SRL: P≤0.0001). In contrast, there was no effect on the regulation of this gene in the GT2a cells. In conclusion, we could identify a highly significant difference in regulation of CCNT1, E2F2 and HAVCR1 between HCV-GT1b and GT2a cells upon mTor inhibitor-treatment. These factors are likely to play a central role in regulation of HCV replication activity by mTor inhibitors and are currently under further investigation.



Poster
P77
Single center analysis of postoperative complications after HVAD implantation
*Ahmed Ahmed1, Nikolaus Pizanis 1, Abdelaziz Shabaneh 1, Rian Urbien2, Janine Gronewold3, Markus Kamler1
1 Universitätsklinikum, Thorakale Transplantation, Essen, Deutschland
2 Katholisches Krankenhaus, Kardiologie, Essen, Deutschland
3 Universitätsklinikum, Biometrie, Essen, Deutschland
Abstract-Text :

Introduction: A third-generation ventricular assist device, the HeartWare Ventricular Assist System, has demonstrated its reliability and durability in clinical experience. However, relatively few studies have examined the full spectrum of complications after HVAD implantation beyond infectious and bleeding events.


Methods: We conducted a retrospective review of 104 patients receiving 3rd generation continuous flow, centrifugal blood pump HeartWare ventricular Assist device HVAD® (HeartWare, Inc., Framingham, Massachusetts) at the department of thoracic organ transplantation, University Hospital Essen, Germany. The study was conducted between August 2010 and March 2015. Frequency and date of onset of postoperative complications in relation to INTERMACS scale were examined.


Results: Overall, the most frequent complications were sepsis (47.1%), right ventricular failure (37.5%) and respiratory failure (33.7%). Within one postoperative week, renal failure was the most common complication followed by right ventricular failure and respiratory failure. Complications that were common between one week and one month postoperatively were sepsis, respiratory failure and right ventricular failure. Stroke was a late complication which occurred most frequently after 6 months. INTERMCAS profile 1 had a significant higher incidence of postoperative respiratory failure (p= 0.013), surgery related hemorrhage (p=0.029) and multiorgan failure (p= 0.014) in comparison to other INTERMCAS profiles.


Conclusions: In this 5-year review, the most common adverse events tended to occur early after HVAD implantation. Preoperative INTERMCAS classification correlates with postoperative complications.



Poster
P78
A thin line between rejection and BK virus infection after heart transplantation
*Markus J. Barten1, Hanno  Grahn1, Meike  Rybczynski1, Alexander Bernhardt1, Hermann Reichenspurner1
1 Universitäres Herzzentrum Hamburg, Klinik für Herz- und Gefäßchirurgie, Hamburg, Deutschland
Abstract-Text :

Background: BK virus (BKV) infection is a sign of over-immunosuppression, however optimal therapy of harmful BKV infections after HTx remains unclear. Here we present an unusual case of BKV infection in a patient with rejection.


Results: Our 32 years old HTx patient suffered from severe cytomegalovirus (CMV) pneumonia induced sepsis and developed renal failure after 4 months. At month 6 the patient had sudden onset of impaired graft function. Cellular-mediated rejection (CMR) was verified by biopsy (ISHLT 2R) and antibody-mediated rejection (AMR) by detection of donor specific antibodies, ultrasound results and clinical symptoms. Rejection therapy was performed with methylprednisolone pulse therapy, 4 cycles of plasmapheresis, immunoglobuline and rituximab.  While graft function recovered renal impairment deteriorated further requiring dialysis with evidence of BK viruria first (copies max. 1x109) and BK viremia (copies max. 7000) later. Consequently, we added leflunomide, administrated CMV-IgG (cumulative 40.000IE / 6 weeks) which also contains antibodies against BKV, lowered Tac-levels (6-8 to 4-6ng/ml) and stabilized everolimus (ERL) levels (3-8ng/ml). Under this treatment RF recovered to almost normal (creatinine 1.6mg/dl), BK viruria could be reduced (copies min. 2x108) and viremia of BKV vanished.


Conclusion: Our case demonstrates how thin the line is between intense and reduced immunosuppression to treat rejection and BKN, respectively.  Adding leflunomide and high doses of CMV-IgG to low TAC- and normal ERL-levels may help to treat BKV infection. However, detection of BKV in patients with either anti-rejection therapy or new onset of nephropathy should become a standard after HTx.



Poster
P79
2-year follow-up after minimally-invasive left ventricular assist device implantation - a single center experience
*Stephanie Schmidt1, Daniel Reichart2, Chantal Brand2, Florian Wagner2, Alexander Bernhardt2, Stefan Blankenberg1, Tobias Deuse3, Hermann Reichenspurner2, Markus Barten2
1 Universitäres Herzzentrum Hamburg, Allgemeine und Interventionelle Kardiologie, Hamburg, Deutschland
2 Universitäres Herzzentrum Hamburg, Herz- und Gefäßchirurgie, Hamburg, Deutschland
3 University of California-San Francisco, Department of Adult Cardiothoracic Surgery, San Francisco, Vereinigte Staaten
Abstract-Text :

Implantation of minimally-invasive left ventricular assist device (mLVAD) avoids a full sternotomy, probably reducing the surgical risk of following transplantations or right ventricular (RV) failure. We demonstrate our results of mLVAD implantation (mLAVD) operated via left lateral thoracotomy compared to LVAD implantation (LVAD) done via full median sternotomy.


Data of 70 patients (mLAVD n=22, 52±15 years; LVAD n=48, 59±11 years), who received a HVAD system (HeartWare®) between 2010 and 2015 were analysed retrospectively. 31.8% (7/22) of mLVAD and 56.3% (27/48) of LVAD were classified as INTERMACS level I/II, whereas 68.2% (15/22) of mLVAD and 43.7% (21/48) of LVAD belonged to INTERMACS level III/IV. In 81.8% (18/22) of the mLVAD the outflow graft was anastomosed to the ascending aorta via right minithoracotomy (n=14) or hemisternotomy (n=4); while 18.2% (4/22) were anastomosed to the descending aorta. Cardiopulmonary bypass was initiated percutaneously into the femoral vessels, 40.9% (9/22) of the mLVAD received a temporary RV support (tRVAD) due to reduced RV-function.


The mLAVD presented a 2-year survival of 59.1%, non-significant superior compared to the LVAD with 47.9% (p=0.62). 6 patients were transplanted during follow-up (mLVAD 2/22, LVAD 4/48) and 3 LVAD-patients were able to be weaned with successive LVAD explantation. A tendency towards less LVAD-specific infections was found in mLVAD (p=0.06). Multiple organ failure was the most common cause of death (mLVAD 3/22, LVAD 12/22). Significant superior survival was seen in patients receiving mLVAD without tRVAD related to patients with LVAD/tRVAD implantation (p=0.022). During the 2-year follow-up RV-failure occurred in 9.1% (mLVAD 2/22) compared to 10.4% in LVAD (5/48) (p>0.05).


MLVAD implantation is a feasible technique and is non-inferior compared to sternotomy and particularly suitable for bridge-to-transplant patients. For prediction and avoidance of RV-failure larger patient cohorts are needed.



Poster
P80
Impact of donor hypernatremia on outcome after cardiac transplantation
*Udo Boeken1, Alexander Albert1, Arash Mehdiani1, Bozena Sowinski1, Anna Kathrin Schmidt1, Ralf Westenfeld2, Payam Akhyari1, Diyar Saeed1, Artur Lichtenberg1
1 Uniklinik, Kardiovaskuläre Chirurgie, Düsseldorf, Deutschland
2 Uniklinik, Kardiologie, Pneumologie und Angiologie, Düsseldorf, Deutschland
Abstract-Text :

Objective: Donor hypernatremia is known to be associated with impaired outcome following liver and renal transplantation whereas its impact on outcome after heart transplantation (htx) is still discussed controversially. The impact of donor sodium levels on early morbidity and 1-year-survival following htx should be investigated.


Methods: Between 2010 and 2017 84 patients underwent htx in our department. With regard to donor sodium levels the patients could retrospectively be divided into three groups: a group with donor sodium below 133 mmol/l (group 1), a group with levels between 133 and 156 mmol/l (gr. 2), and a third group with donor sodium > 156 mmol/l (gr. 3).


Results: Htx was performed in 9 patients with donor levels below 133 mmol/l, in 63 patients with donor sodium between 133 and 156 mmol/l, and in 12 patients with levels > 156 mmol/l.


Thirty-day-mortality was 11.1 % in patients of gr. 1,  9.5 % in gr. 2 and 16.7 % in gr. 3.


We did not find significant differences between the groups regarding incidence of rejection, renal failure, or severe infection.  Duration of mechanical ventilation, stay on intensive care unit and in hospital was slightly prolonged in groups 1 and 3.


1-year-follow up revealed a comparable morbidity between the groups. Coronary allograft vasculopathy occurred only in 2 patients of group 2. The survival rate was 83.3 % (5/6), 77.4 % (41/53), and 72.7 % (8/11) in groups 1,2, and 3.


Conclusions: We could not detect an impaired  early outcome in patients receiving hearts from hypernatremic donors. As the 1-year-follow-up results were also comparable between our groups, we think that cardiac allografts from donors with elevated sodium levels can be transplanted with satisfying results.



Poster
P81
Calcineurin inhibitor withdrawal and pre-operatively ventricular assist device support results in de-novo donor specific antibodies triggering cardiac allograft vasculopathy
*Markus J. Barten1, Johannes Tauber1, Meike Rybczynski1,2, Hanno Grahn2, Alexander Bernhardt1, Hermann Reichenspurner1
1 Universitäres Herzzentrum Hamburg, Klinik für Herz- und Gefäßchirurgie, Hamburg, Deutschland
2 Universitäres Herzzentrum Hamburg, Klinik für Allgemeine und Interventionelle Kardiologie, Hamburg, Deutschland
Abstract-Text :

Background:


Existing renal failure (RF) pre-heart transplantation (HTx) is a risk factor for decreased survival post-HTx. RF often aggravates due to the chronic use of calcineurin inhibitors (CNI). Thus, for many years CNI weaning strategies have been made to avoid RF.


Case Report:


Our 31-year-old male patient was supported with continuous flow left ventricular assist device (cfLVAD) for 6 months. Post-HTx, induction therapy with antithymocyte globuline was implemented because of existing impaired renal function to delay the start with tacrolimus (TAC).


The initial clinical course of the patient was uneventful besides persistent RF (cGFR 38 ml/min). Biopsy showed no sign of cellular rejection (CR, 0R) at month 6. Thus, we started to wean off TAC to a CNI-free regimen with everolimus (ERL), MMF and steroids at month 9.


At month 10 the patient presented with signs of heart failure because of decreased systolic LV-function and diastolic dysfunction. Biopsy ruled out cellular rejection but detected a form of diffuse CAV affecting the media. We detected dnDSA and a mild CAV (ISHLT grade 1) in the angiography. Therapy of dnDSA consisted of methylprednisolone pulses and reinitiation of TAC to the existing regimen. Moreover, we treated with plasmapheresis, immunoglobulins and rituximab three times over 3 months, followed by extracorporeal photophoresis as chronic therapy.


Clinical symptoms of heart failure disappeared and heart function was restored at the end of therapy. 11 months later biopsy showed no CR and CAV. Renal function remains reduced but stable (cGFR 54 ml/min) and the patient is back to work.


Conclusion:


Our case shows that patients with cfLVAD support pre-HTx are more prone to develop dnDSA post-HTx. In such immunologic risk patients with RF CNI-minimizing rather than CNI-withdrawal strategies should be preferred combined with a close monitoring of dnDSA.



Poster
P82
Gender differences in heart transplant recipients
Christina Magnussen1, Nicole Ruebsamen1, Francisco M. Ojeda1, Stefan Blankenberg1, Hermann Reichenspurner2, Renate B. Schnabel1, *Alexander Bernhardt2
1 Universitäres Herzzentrum Hamburg, Interventionelle und allgemeine Kardiologie, Hamburg, Deutschland
2 Universitäres Herzzentrum Hamburg, Herz- und Gefäßchirurgie, Hamburg, Deutschland
Abstract-Text :

Background: Differences in symptoms, disease course and treatment of heart failure between women and men are known. Possible gender differences in indications, procedural characteristics and outcome are not well established. We aimed to examine gender aspects in heart transplantation and perioperative outcome.


Methods: In N=41,830 first time heart transplant recipients 22.7% were women, We analyzed the prospective international United Network of Organ Sharing (UNOS) database. We followed patients for total mortality and the incidence of adverse events such as graft failure, allograft vasculopathy and malignancies.


Results: At transplant, women were younger than men (median age 52 vs. 55 years, p<0.001) suffered less likely from ischemic cardiomyopathy (7.4% in women vs. 18.7% in men, p<0.001) and were less frequently bridged by mechanical circulatory support (14.5% in women vs. 19.6% in men, p<0.001). Transplant urgency was comparable (status 1A at transplant 23.5% in women vs. 25.5% in men, p<0.001). 


Patients were observed for a median of 10 years (maximum follow-up time was 26.3 years). We observed 17,937 deaths during follow-up. Survival post heart transplantation was comparable in women and men (hazard ratio (HR) 0.99, 95% confidence interval [0.95, 1.02], p=0.43). There was a trend for higher graft failure for women (HR 1.08 [0.99, 1.19], p=0.084) and significantly lower allograft vasculopathy (HR 0.86 [0.82, 0.89], p<0.001) and malignancy (HR 0.61 [0.57, 0.65], p<0.001).


Conclusion: Women and men differed in indication and procedural characteristics for heart transplantation. Overall survival after heart transplantation was comparable, but the incidence of adverse events was different for women and men. Whether the knowledge on gender differences in patient characteristics and gender-specific risk prediction can support clinical decisions and improve outcome, needs to be shown.



Poster
P83
Tolerogenic properties of B-cells in solid-organ transplantation
Benjamin Wilde1, *Sonja Schimo2, Fabio Ius3, Ulrich Gockel2, Gregor Warnecke3, Oliver Witzke4
1 University Hospital Essen, University Duisburg-Essen, Department of Nephrology, Essen, Deutschland
2 Biotest AG, , Dreieich, Deutschland
3 Hanover Medical School, Department of Cardiothoracic, Transplant and Vascular Surgery, Hanover, Deutschland
4 University Hospital Essen, University Duisburg-Essen, Department of Infectious Diseases, Essen, Deutschland
Abstract-Text :

Introduction and Background: Achieving immune tolerance is the ultimate goal in solid-organ transplantation. Despite advanced immunosuppressive regimens, allograft rejection remains a severe problem. Several strategies aim at depleting deleterious alloantibody-producing B cells; however, distinct subsets with immunomodulatory function, termed Bregs, may also be targeted. This subgroup has been ascribed tolerogenic properties mediated by the expression of immunosuppressive mediators, such as interleukin-10 (IL-10), Granzyme B (GrB), inhibitory cell-surface receptors or by the secretion of protective antibodies (in particular IgM).


Methods: The effect of immunosuppressive drugs on regulatory B-cell subsets, including transitional immature B lymphocytes (CD19 CD24hiCD38hi) and GrB-producing B cells, was assessed in renal-transplant patients receiving calcineurin inhibitors (CNI). Furthermore, a complementary literature search on innate-like B cells was conducted, emphasizing the central role of IgM in allograft tolerance.


Results and Conclusions: The number of peripheral circulating CD19 CD24hiCD38hi and IL‑10-producing Bregs was significantly reduced in CNI-treated patients and in healthy volunteers receiving CNI. In contrast, the number of GrB-producing regulatory B cells was not affected by CNI. A low percentage of peripheral blood CD19 CD24hiCD38hi Bregs in renal-transplant patients correlated with a higher incidence of allograft rejection. A similar association has been reported for transplant patients with low serum IgM levels. IgM may directly exert selective pressure on auto-reactive and donor-reactive B-cell clones, also explaining the high DSA clearance rate in lung transplant patients treated with IgM-enriched IVIGs. In conclusion, immunosuppressive therapies should aim to deplete B cells selectively and to preserve the regulatory B‑cell subsets that are important for the maintenance and induction of allograft tolerance.



Poster
P84
Akutes Leberversagen im 2. Lebensjahr – LTX mit folgendem multisystemischen therapierefraktären Autoimmungeschehen verursacht durch einen Mangel der ITCH E3 Ubiquitin Ligase
*Nicola Kleine-Eggebrecht1, Christian Staufner2, Dominic  Lenz2, Bianca Hegen1, Denisa Pilic1, Simone  Kathemann1, Christoph Hünseler3, Eva Tschiedel1, Magdelin Elgizoul1, Andreas Paul1, Holger Prokisch2, Peter Hoyer1, Elke Lainka1
1 Uniklinik Essen, , Essen, Deutschland
2 Uniklinik Heidelberg, , Heidelberg, Deutschland
3 Uniklinik Köln, , Köln, Deutschland
Abstract-Text :

Hintergrund: Ubiquitin ist ein Protein, das u.a. an der Proteinqualitätskontrolle beteiligt ist. Biallelische Mutationen im Gen ITCH (Chromosom 20q11) führen zum Mangel der E3 Ubiquitin Ligase. Folgen sind eine erhöhte T-Zellaktivität mit fehlender Immuntoleranz und die Manifestation einer komplexen systemischen Autoimmunerkrankung.


Fallbeschreibung: 9/11 wurde ein einjähriges Mädchen konsanguiner Eltern bei akutem Leberversagen mit V.a. drug-induced hypereosinophilic syndrome bei positiven LKM-2 Antikörpern lebertransplantiert. Zudem fielen Dystrophie, Kleinwuchs, psychomotorische Retardierung und muskuläre Hypotonie auf. Im Verlauf entwickelten sich Kortikoidsteroid-sensible Abstoßungsreaktionen sowie eine systemische Autoimmunerkrankung mit Nachweis spezifischer Antikörper (de-novo-Autoimmunhepatitis, Thyreoiditis mit Exophthalmus, Diabetes mellitus Typ I, Immunneutropenie). Histologisch wurde eine Leberzirrhose mit lobulären Entzündungsinfiltraten, Riesenzellhepatitis und duktopenischer Rejektion bei chronischer Cholestase verifiziert. Nach Re-LTX 8/15 zeigte sich eine vergleichbare Leberhistologie. Weitere Komplikationen waren eine Adenovirus-Hepatitis, pulmonale Aspergillose, MRSA und E. coli Sepsis. Wegen therapierefraktärer Panzytopenie bei portaler Hypertension mit Hypersplenismus wurde eine lymphoproliferative Erkrankung mittels Knochenmarksbiospie ausgeschlossen. Bei progredienter Panzytopenie erfolgten regelmäßige EK- und TK Transfusionen sowie Immunglobulingaben. 10/16 kam es zu epi- und subduralen Blutungskomplikationen mit fokalen Krampfanfällen. Drei Monate später verstarb das Mädchen i.R. einer Sepsis zuhause. Postmortem ergab eine Whole Exome-Sequenzierung (WES) eine homozygote Mutation im Gen ITCH.


Schlussfolgerung: Mutationen in ITCH führen zu einer schweren systemischen Autoimmunerkrankung, welche sich mit akutem Leberversagen manifestieren kann. Dies verdeutlicht die Wichtigkeit der Ubiquitin-Signalwege und den Einfluss auf das Immunsystem. 



Poster
P85
How evaluation for living kidney donation saved my life
*Thomas Mühlbacher1, Eva-Carina Magunia1, Silvio Nadalin2, Nils Heyne1, Martina Guthoff1
1 University of Tübingen, Dept. of Internal Medicine IV, Section of Nephrology and Hypertension, Tübingen, Deutschland
2 University of Tübingen, Dept. of General-, Visceral- and Transplantation Surgery, Tübingen, Deutschland
Abstract-Text :

Purpose: In order to ensure eligibility for living kidney donation, donor candidates undergo a thorough medical evaluation. This evaluation process might reveal previously unknown medical conditions, leading to declination of the donor candidate. However, detection of such medical conditions may have a lifesaving impact for kidney donor candidates. We report 10-year data from our living donor transplantation program on donor candidates newly diagnosed with impactful medical conditions during the evaluation process.


Methods: A retrospective analysis of living kidney donor candidates since 2007 at our center was performed. Focus was on newly diagnosed medical conditions requiring immediate attention and their prognostic significance.


Results: Since 2007, 341 potential living kidney donor candidates were evaluated, of which 157 (46%) donated a kidney. 174 candidates (51%) were declined, whereas 10 candidates (4%) are still under evaluation. Interestingly, 48 of the declined candidates (28%) were diagnosed with a medical condition requiring immediate attention. While 29 patients were newly diagnosed with diabetes mellitus, 8 patients were diagnosed with cardiac disease requiring intervention and 7 patients were diagnosed with malignancy. These newly diagnosed malignancies comprised NET of the bowel and abdomen, lymphoma, bronchial carcinoma, MGUS and renal cell carcinomas, which directly underwent curative treatment. The other 4 patients were newly diagnosed with CIBD, active hepatitis B or PSC, respectively.


In conclusion, the evaluation process for living kidney donation allowed for revelation of life changing diagnoses in a relevant proportion of candidates, requiring immediate medical attention in order not to affect life expectancy.



Poster
P86
Langzeit-Auswirkungen einer Nieren-Lebend-Spende auf die kognitive Leistungsfähigkeit der Spender (NEUROKID-Studie)
*Marie Mikuteit1, Faikah Gueler2, Iris Pollmann3, Henning Pflugrad1, Meike Dirks1, Martina de Zwaan3, Karin Weissenborn1
1 Medizinische Hochschule Hannover, Neurologie, Hannover, Deutschland
2 Medizinische Hochschule Hannover, Nephrologie, Hannover, Deutschland
3 Medizinische Hochschule Hannover, Psychosomatik, Hannover, Deutschland
Abstract-Text :

Einleitung und Fragestellung: Die Nierenlebendspende hat einen Anteil von 25-30% an den Nierentransplantationen in Deutschland. Über das Langzeit-Outcome der Spender ist bisher wenig bekannt. Dies gilt insbesondere für eventuelle Einflüsse auf Kognition, Psyche und Lebensqualität. Ziel der Studie ist zu untersuchen, ob sich Nierenlebendspender diesbezüglich von gesunden Kontrollen unterscheiden.


Methodik: Alle 391 Spenderinnen und Spender, die an der MHH zwischen 2003 und 2012 eine Niere gespendet haben, wurden zur Teilnahme an der Studie eingeladen. Ausschlusskriterien waren Alter >70 Jahre, ZNS-wirksame Medikation, neurologische oder psychiatrische Erkrankung und Sprachbarriere. Die ersten 60 Patienten, die teilnehmen wollten und die Einschlusskriterien erfüllten, wurden schließlich mittels Aufmerksamkeits- und Gedächtnistests untersucht, und füllten Selbsterhebungsbögen zur Lebensqualität und Fatigue-Symptomatik aus. Die Ergebnisse wurden mit den jeweiligen Normen und den Daten eines nach Alter und Schulbildung angepassten Kollektivs gesunder Probanden verglichen. Zusätzlich wurde die Nierenfunktion (eGFRCDK-EPI) direkt nach Spende und bei Studienteilnahme erfasst.


Ergebnisse: 56,8 % der untersuchten Spender waren Frauen. Das mittlere Alter zum Untersuchungszeitpunkt lag bei 58,2 ± 6,9 Jahren, seit der Spende waren im Mittel 96,8 ±37,9 Monate vergangen. Die eGFR hatte sich von im Mittel 60,5 ± 9,5 ml/min unmittelbar nach der Spende auf 63,3±8,1 ml/min bei Studienteilnahme gebessert. Aufmerksamkeits-und Gedächtnisleistung, Fatigue und Lebensqualität der Spender unterschieden sich nicht signifikant von denen der Kontrollen. Auch zeigte sich keine Korrelation zwischen den neuropsychologischen Parametern oder den SF12 Scores und der aktuellen eGFR.


Schlussfolgerung: Insgesamt lagen kognitive Leistungsfähigkeit, Lebensqualität und Fatigue-Score der untersuchten Nierenlebendspender im Normbereich.



Poster
P87
Nierenlebendspende – Entsprechen die Prognosen für die Nierenfunktion des Spenders den tatsächlichen Ergebnissen?
*Faikah Gueler1, Naila  Ahmed1, Alkan Gündüz1, Georg Berding2, Lars Pape3, Mario Schiffer1, Anke Schwarz1, Harald Schrem4, Hermann Haller1, Nicolas Richter5, Wilfried Gwinner1
1 Medizinische Hochschule Hannover, Nephrologie, Hannover, Deutschland
2 Medizinische Hochschule Hannover, Nuklearmedizin, Hannover, Deutschland
3 Medizinische Hochschule Hannover, Pädiatrische Nephrolgoie, Hannover, Deutschland
4 Medizinische Hochschule Hannover, Qualitätsmanagement IFB-tx, Hannover, Deutschland
5 Medizinische Hochschule Hannover, Viszeralchirurgie, Hannover, Deutschland
Abstract-Text :
Jeder Nierenlebendspender hat erwartungsgemäß einen Verlust an Nierenfunktion nach Nephrektomie. Wichtig ist im Vorfeld abzuschätzen wie groß dieser Verlust sein wird. 110 konsekutive Nierenlebendspenden zwischen 2013 und 2017 im Hinblick auf die zu erwartende Nierenfunktion nach Nierenspende wurden analysiert.
Die Kreatinin basierte eGFR(CKD-EPI), die gesammelte Kreatinin-Clearance und die seitengetrennte Isotopen-Nephrographie vor Spende wurden untersucht. Post-operativ wurde die Nierenfunktion gleich nach OP, nach 3-6 Wochen und 12 Monaten analysiert.
Das Spenderalter in dieser Studie lag zwischen 21 und 72 Jahren. Die meisten Spenden waren Eltern für Kinder (37%) und Ehepaare untereinander (31%). Bei den 21-40 Jährigen (n=11) war die eGFR vor Spende am höchsten (107±9,8 ml/min), nach Entnahme bei 59±8,3ml/min. Die erwartete Nierenfunktion unter Berücksichtigung des Seitenanteils (entsprechend der Isotopen-Nephrographie) war geringfügig (-4%) niedriger als der tatsächlich gemessene Wert nach OP. Bereits innerhalb von 6 Wochen kam es zu einem eGFR-Anstieg um 11% und nach 12 Monaten um 23% (73±10 ml/min). In der 4. Altersdekade (n=42) waren die Prognosen für die unmittelbare post-operative Nierenfunktion zutreffend. Die mittlere eGFR nahm um 9% in den ersten 6 Wochen und um 16% (59,1±8,7 ml/min) innerhalb von 12 Monaten zu. Bei den 51-60 Jährigen (n=41) waren die Ergebnisse vergleichbar mit den 41-50 Jährigen. Bei >60 Jährigen war eine geringe Verbesserung der Nierenfunktion innerhalb von 6 Wochen nach Spende um 11% zu beobachten, die nach 12 Monaten stabil blieb (50,1±11 ml/min).
Zusammenfassend zeigte sich, dass die Prognose zur Höhe der Nierenfunktion nach Spende unter Berücksichtigung der eGFR und der Seitenverteilung in der Isotopen-Nephrographie der post-operativ gemessenen Nierenfunktion entsprach. Kompensatorische Funktionszunahmen der verbliebenen Einzelniere sind in allen Altersstufen nachweisbar.


Poster
P88
A rare complication after retroperitoneoscopic donor nephrectomy
*Malwina Bialobrzecka1, Lea Berger1, Andreas Wunsch1, Peter Schenker1, Thomas Klein2, Richard Viebahn1
1 KK Bochum, Chirurgie, Bochum, Deutschland
2 MH Herne, Innere Medizin, Herne, Deutschland
Abstract-Text :

Introduction:


Retroperitoneoscopic nephrectomy is an established method of kidney donation. We present a case of an ipsilateral pneumothorax with cervical and mediastinal emphysema as a rare complication of this procedure.


Case:


A 34-year-old woman underwent a left-sided retroperitoneoscopic nephrectomy There were no abnormalities in the preoperative investigations. 


Postoperatively she complained of dyspnea and pain in the operated region. The hemoglobin level remained stable, abdominal ultrasound showed no free fluid collection.


On the third postoperative day, after the removing of the central venous line the patient had a brief loss of consciousness and was transferred to ICU. A CT scan showed a low amount of a fluid with a small pneumothorax on the left side and a mediastinal and cervical emphysema. There were no intracranial abnormalities and no significant lesions in the abdomen. The patient underwent a bronchoscopy which showed no tracheal lesion. The thoracoscopy confirmed the presence of a hemothorax which was evacuated. Two chest tubes were placed and removed. after 72 h. On the 11th postoperative day the patient could be discharged.


Discussion:


In the literature, there are some reports about this complication following retroperitoneoscopic surgery. The most common mechanisms are barotrauma, diaphragmatic injuries or congenital diaphragmatic defects.


Conclusion:


Pneumothorax can occur without any diaphragmatic injury. The compliance of the retroperitoneal space is lower than that of the intraperitoneal cavity. Therefore, a sudden increase in pressure may result in the rupture of tissues. Paying attention to overall pressure limits and end tidal CO2-levels as well as adequate muscle relaxation might in some cases prevent the occurrence of that rare complication.



Poster
P89
Charakterisierung und Outcome des Regensburger Lebendspenderkollektivs
*Antonia Schuster1, Paula Franke1, Daniel Zecher1, Christina Hackl2, Tobias Bergler1, Bernhard Banas1
1 Universitätsklinikum Regensburg, Abteilung für Nephrologie, Regensburg, Deutschland
2 Universitätsklinikum Regensburg, Klinik für Chirurgie, Regensburg, Deutschland
Abstract-Text :

Einleitung: Stagnierende Zahlen an postmortalen Organspendern und eine zunehmend längere Wartezeit läßt die Nierenlebendspende weiter an Bedeutung gewinnen. In Studien konnte gezeigt werden, dass eine Lebendspende für den Transplantatempfänger mit einem besseren Outcome bzgl. der Transplantatfunktion einhergeht, ausführliche Daten bezüglich des Outcomes der Spender hinsichtlich renaler, kardiovaskulärer und allgemein-internistischer Endpunkte in einem kaukasischen Kollektiv liegen jedoch nicht vor. Diese wären jedoch umso wichtiger, um mögliche Risikofaktoren für eine Nierenlebendspende zu identifizieren und somit die Voraussetzungen für selbige zu optimieren.


Methodik: Die Analyse des Regensburger Lebendspenderkollektivs der Jahre 1996-2016 war Ziel der aktuellen Untersuchung. Dabei wurden sämtliche Lebendspender bei denen die Nierenspende realisiert wurde, in die Untersuchung miteingeschlossen (n = 242). Neben den Baselinecharakteristika, die demographische, renale (z.B. Kreatinin, eGFR, Albuminurie, Nierenmorphologie, etc.), kardiovaskuläre und andere Vorerkrankungen umfassten, wurden die Nierenspender Langzeit nachverfolgt (Follow-up nach 1, 2, 3, 5, 10, >10 Jahre). Im Follow-up wurden definierte renale, kardiovaskuläre und andere Endpunkte (wie z.B. Tumorinzidenz) nachverfolgt, ebenso wie Risikofaktoren für selbige, wie z.B. Inzidenz von Hypertonie, de-novo-Diabetes, Nikotinkonsum, untersucht (i. S. 56 Einzelparameter).


Ergebnisse und Schlussfolgerungen: Nach abgeschlossener Analyse der Baselinecharakteristika (Mittelwerte: Alter 53 Jahre, Kreatinin 0,78mg/dl, BMI 26kg/m², eGFR 96ml/min, Albuminurie 7,6mg/gKrea), folgt gegenwärtig die Auswertung der Follow-up Daten (Ergebnisse zum DTG vorliegend). Durch die Analyse von Baseline-, sowie Follow-up-Daten von Nierenlebendspendern soll die Erkenntnis gesteigert und eventuelle Langzeit-Risikofaktoren identifiziert werden.



Poster
P90
The influence of living and deceased donor kidney transplantation on graft survival: A propensity score matched analysis
*Indra  Marcheel1, Julia Stupak1, Jill Gwiasda1, Alexander Kaltenborn1,2, Jan Beneke1, Jürgen Klempnauer3, Harald Schrem1,3
1 Hannover Medical School, Core Facility Quality Management and Health Technology Assessment in Transplantation, Integrated Research and Treatment Center-Transplantation (IFB-Tx), Hannover, Deutschland
2 Federal Armed Forces Hospital Westerstede, Department of Trauma and Orthopedic Surgery, Westerstede, Deutschland
3 Hannover Medical School, Department of General, Visceral and Transplant Surgery, Hannover, Deutschland
Abstract-Text :

Introduction and background


This study evaluates the influence of living related kidney transplantation (n=404) on graft survival beyond pre-operative differences in comparison to deceased donor (n=1549) kidney transplant in a propensity score matched analysis.


Methods


Via propensity scoring, patients were matched for comparing living related to deceased donor organ transplantation. Different propensity score based matching strategies were deployed due to severe differences between the cohorts. Graft survival was analyzed with multivariable Cox regression and Kaplan Meier analysis.


Results and Conclusions


Before adjustment by propensity score matching, graft survival after living related kidney donation is better as compared to deceased donors in Kaplan Meier analysis (p<0.001; log rank) and multivariable Cox regression (p=0.001; HR=0.539).


Propensity score matching required adjustment due to vast differences between patient groups. Although CIT (cold ischemic time) and duration of dialysis were part of the score, they could not both be deployed in matching because this returned a small sample size (n=2x7). Thus, the first of two matching strategies included duration of dialysis while discarding CIT from propensity matching. The second strategy excluded both variables.


Deploying the first matching strategy showed that hypertension in donors was the only independent risk factor for graft loss (p=0.040; HR: 2.998) while living related donation was no significant influence on graft survival (p=0.389).


Deploying the second matching strategy showed that female donor gender (p=0.028; HR: 2.727) was a risk factor while recipient IgA nephropathy (p=0.040; HR: 0.221) and living donation (p=0.021; HR: 0.398) were independent protective factors for graft survival.


Kidney transplantation after short duration of dialysis is most beneficial for patients, differences between living related and deceased donor organs fade when transplantation is performed early.



Poster
P91
FGF1 and AKT activation in C5aR2 deficient mice is associated with protection from ischemia reperfusion injury
*Anja Thorenz1, Katja Hueper2, Christoph Schroeder3, Rongjun Chen1, Song Rong1, Martin Meier4, Jan Hinrich Bräsen5, Andreas Klos6, Hermann Haller1, Bennet Hensen2, *Faikah Gueler1
1 Medizinische Hochschule Hannover, Nephrologie, Hannover, Deutschland
2 Medizinische Hochschule Hannover, Radiologie, Hannover, Deutschland
3 Sciomics, , Heidelberg, Deutschland
4 Medizinische Hochschule Hannover, Imaging Center des Institutes für Versuchstierkunde, Hannover, Deutschland
5 Medizinische Hochschule Hannover, Pathologie, Hannover, Deutschland
6 Medizinische Hochschule Hannover, Mikrobiologie, Hannover, Deutschland
Abstract-Text :

Ischemia reperfusion injury (IRI) causes rapid complement activation and acute kidney injury (AKI) and contributes to delayed graft function after solid organ transplantation. Severe AKI can progress into renal fibrosis Here we studied the distinct functions of complement 5a receptor 1 and 2 (C5aR1; C5aR2) a well-established renal IRI and fibrosis model using C5aR1 and C5aR2 deficient mice in comparison to wild type (WT) mice. IRI was induced by 45 min unilateral renal IRI and longitudinal follow up for 1, 7 and 21 days was done by histology, mRNA analysis and functional magnetic resonance imaging (fMRI). Differential protein abundance and phosphorylation status were assessed with high content antibody microarrays and Western blotting. C5aR-/- mice developed less IRI-induced inflammation and fibrosis than WT mice. C5aR2-/- showed remarkable renal regeneration after IRI which was even more pronounced than in C5aR1-/- mice. Significant up-regulation of the anti-inflammatory IL-10 mRNA in combination with markedly enhanced tubular proliferation and improved renal perfusion were observed in C5aR2-/- IRI kidneys. In vivo lectin staining of the glycocalyx demonstrated increased patency of peritubular capillaries in C5aR2-/- mice. Proteomics revealed enhanced abundance of AKT and increased phosphorylation of fibroblast growth factor (FGF1) in C5aR2 -/- IRI kidneys which was confirmed by Western blotting. C5aR1 and C5aR2 deficient mice are partially protected from renal inflammation after IRI. C5aR2-/- kidneys exhibit better renal regeneration and perfusion than those of C5aR1-/-. This was associated with enhanced expression of anti-inflammatory IL-10, pro-angiogenic FGF1 and the pro-survival factor AKT in C5aR2 deficient animals indicating that C5aR2 inhibition might be a novel therapeutic target to prevent AKI and to overcome delayed graft function.



Poster
P92
Charakterisierung der Zellschädigung von Lungenepithelzellen durch Kaltlagerung / Wiedererwärmung
*Katharina Kettler1, Björn Walter1, Ursula Rauen1
1 Universitätsklinikum Essen, Institut für Physiologische Chemie, Essen, Deutschland
Abstract-Text :

Einleitung:


Kälte löst in verschiedenen Zelltypen, u.a. in Lungenepithelzellen, eine apoptotische Schädigung aus, die über redoxaktive Eisenionen vermittelt wird. Inwieweit die Schädigung auch durch Ferroptose-Inhibitoren beeinflussbar ist und / oder ob nekroptotische Vorgänge hereinspielen, ist derzeit unbekannt. Zudem ist für Lungenepithelzellen noch nicht bekannt, ob es bei Kaltlagerung, wie in einigen Zelltypen, zu einer zusätzlichen Zellschädigung durch chloridreiche oder, wie bei anderen Zelltypen, durch chloridarme Lösungen kommt.


Methodik:


Die humane Lungenepithel-Zelllinie A549 wurde in Krebs-Henseleit-Puffer (KH; Cl-: 128 mM) und einer chloridarmen Variante (KH-Lac; weitgehender Ersatz von Cl- durch Lactobionat, Cl-: 5 mM) in An- und Abwesenheit des Eisenchelators Desferal (1 mM), des Nekroptose-Inhibitors Nekrostatin (50 µM), des Ferroptose-Inhibitors Ferrostatin (5 µM) sowie dem Lösungsmittel letzterer (DMSO) für 168 h bei 4 °C gelagert, dann in Zellkulturmedium (DMEM) wiedererwärmt. Zellschädigung (LDH-Freisetzung), Lipidperoxidation (TBARS) und Zellmorphologie wurden bestimmt.


Ergebnisse und Schlussfolgerung:


Nach 168 h bei 4 °C in KH ± DMSO wurde eine Zellschädigung von 80 - 85% bereits nach der Kaltlagerung beobachtet, in KH-Lac ± DMSO lag diese bei 65 - 70%. Nekrostatin hemmte die Schädigung nur um ≤ 15 %. Desferal und Ferrostatin hingegen hemmten die Kälteschädigung fast komplett (LDH-Freisetzung ≤ 5 % in KH, ≤ 12 % in KH-Lac). Kaltinkubation führte zur Lipidperoxidation, die ebenfalls durch Desferal und Ferrostatin gehemmt wurde. Wiedererwärmung der in KH Desferal oder KH Ferrostatin kaltinkubierten Zellen führte nicht zu weiterer Schädigung (Gesamtschädigung ≤ 10 %, normale Zellmorphologie), während diese bei in KH-Lac mit beiden Inhibitoren kaltinkubierten Zellen die Zellschädigung erhöhte und massives Blebbing der Zellen auslöste. Die Wiedererwärmungskomponente nach chloridarmer Kaltlagerung gilt es nun zu untersuchen.



Poster
P93
Silencing of MHC class I on primary human hepatocytes as a novel strategy for reduction of alloreactivity – a preliminary in-vitro study
*Constança  Figueiredo1, *Felix  Oldhafer2, Moritz Kleine2, Oliver Beetz2, Eva-Maria Wittauer2, Chen Chen-Wacker 1, Marco Carvalho-Oliveira 1, Frank Lehner2, Reiner Blasczyk1, Florian  Vondran 2,3
1 Hannover Medical School, Institute for Transfusion Medicine, Hannover, Deutschland
2 Hannover Medical School, ReMediES, Department of General, Visceral and Transplant Surgery, Hannover, Deutschland
3 German Centre for Infection Research (DZIF), , Hannover, Deutschland
Abstract-Text :

Introduction and Background:


Hepatocyte transplantation (HTx) is of large potential as an additional treatment modality for various liver diseases. However, success of HTx is limited by insufficient engraftment/long-term acceptance of cellular allografts due to immunological rejection. Alternative strategies of immunomodulation thus are of special interest. Primary human hepatocytes (PHH) are known to constitutively express MHC class I, consequently silencing of MHC class I expression could potentially reduce the allogeneic immune responses induced upon transplantation and hence improve the outcome of HTx.


Methods:


PHH were isolated using a 2-step-collagenase perfusion technique. Expression of MHC class I was silenced using lentiviral vectors encoding for β2-microglobulin (shβ2m) specific short hairpin RNA (shRNA). A non-specific shRNA (shNS) was used as control. Thereafter PHH were co-cultured with allogeneic lymphocytes (labeled with PKH-26) in terms of a mixed lymphocyte hepatocyte culture (MLHC). Proliferative responses were detected on day 10 of MLHC via flow-cytometry.


Results and Conclusions:


The delivery of shβ2m into PHH caused a decrease by up to 87% in β2m transcript levels in comparison to shNS. This induced the downregulation of MHC class I cell surface expression by 70%±12% in comparison to shNS-expressing PHH. Subsequently, proliferative responses against silenced PHH were significantly lower than observed for untreated PHH (mean reduction of 60%). Preliminary in-vitro data thus indicate that silencing of MHC class I on PHH might represent a promising approach for immunomodulation in the transplant setting.



Poster
P94
Immunosuppressive drugs in hepatocyte transplantation - An in vitro analysis with primary human hepatocytes
*Felix  Oldhafer1, Michael Fabian 1, Christine Falk 2,3, Eva-Maria Wittauer1, Daphne DeTemple 1, Moritz Kleine1, Oliver Beetz1, Kai Timrott4, Frank Lehner1, Michael  Bock2,5, Florian  Vondran 1,2
1 Hannover Medical School, ReMediES, Department of General, Visceral and Transplant Surgery, Hannover, Deutschland
2 German Centre for Infection Research (DZIF), , Hannover, Deutschland
3 Hannover Medical School, Institute of Transplant Immunology, Hannover, Deutschland
4 Medizinische Hochschule Hannover, , Hannover, Deutschland
5 Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Deutschland
Abstract-Text :

Introduction


Hepatocyte transplantation (HCTx) is of great potential for the treatment of various liver diseases. Despite successful animal studies, insufficient engraftment and long-term acceptance of cellular allografts though remain major challenges for clinical application in humans. Aim of this study thus was to analyse different immunosuppressive drugs for their potential suitability in HCTx applying an in vitro model with primary human hepatocytes (PHH).


Methods


PHH were isolated from resected liver specimens and co-cultured with allogenic lymphocytes in terms of a mixed lymphocyte hepatocyte culture (MLHC) to characterize the immune response induced. Proliferative alloresponses were determined by flow-cytometry. MLHC was performed in the absence/presence of Cyclosporin, Everolimus, Belatacept and methylprednisolone. The viability and metabolic competence of cultured PHH was assessed by the following parameters: MTT-assay, DNA content, albumin synthesis, urea production and AST-leakage.


Results


Immune responses towards PHH in vitro effectively could be suppressed by Cyclosporin, Everolimus and Belatacept. In contrast to the other immunosuppressants, the application of Everolimus significantly reduced the viability of PHH in vitro. However, further analyses including the courses of DNA content, album synthesis, urea production and AST-leackage showed no significant differences in between the immunosuppressive drugs applied.



Poster
P95
Personal experiences with a new training concept in establishment of orthotopic rat liver transplantation
*Weiwei Wei1, Olaf Dirsch2, Utz Settmacher1, Uta Dahmen1
1 Jena University Hospital, Department of General, Visceral and Vascular Surgery, Jena, Deutschland
2 Klinikum Chemnitz gGmbH, Pathology, Chemnitz, Deutschland
Abstract-Text :

Background:


Rat liver Transplantation (LTx) is important animal model to investigate the mechanisms of liver graft rejection and liver ischemia/reperfusion injury. It has been reported that at least 30 procedures was needed to achieve the first survival. We want to facilitate the learning curve of Kamada technique for rat LTx using new learning concept "video-assisted PDCA (plan-do-check-act) circle".


Methods:


The new concept consists of 3 components: theoretic preparation, stepwise practice and problem analysis. In theoretic preparation we learned the anatomy and procedures of LTx. Then microsuture anastomosis, cuff technique anastomosis and splint technique were practiced stepwise in "PDCA circle" in rat bodies. Each practice was well planned, video-monitored and photodocumented, both of which were in detail analyzed to identify the problem. The solution was planned and implemented in the next round practice. The whole procedures were thereafter trained using "PDCA concept". Histologic results were analyzed. At last, we reviewed existing training concepts and their schedules.


Results:


After 10 rounds practice, the microsuture anastomosis was handsewed in 10 min with solving the problems (stomal stenosis, leakage and rupture).


After 15 rounds practice, the cuff anastomosis was finished in 3 min with solving the problems (vessels rupture, cuff torsion, kinking and dislocation).


After 5 rounds practice, the splint anastomosis was performed in 3 min with solving the problems (bile duct rupture, bleeding and retraction).


After 13 rounds practice on liver rats, the first 24 hours-survival was achieved with anhepatic time 25min. Histological examination confirmed the surgical quality.


Conclusion:


The new learning concept "video-assisted PDCA circle" can facilitate the learning curve of rat LTx and to reduce the numbers of training animal significantly.



Poster
P96
Optimismus und Adhärenz nach Nierentransplantation
*Daria Tkachenko1, Luisa Peters1, Laura Franke1, Tanja Zimmermann1
1 Medizinische Hochschule Hannover, Institut für Psychosomatik und Psychotherapie, , Hannover, Deutschland
Abstract-Text :

Einleitung: Ein großes Problem mit welchem sich die Nierentransplantationsmedizin konfrontiert sieht, ist die hohe Zahl an Transplantatverlusten durch mangelnde Adhärenz an die immunsuppressive Medikation. Studienergebnisse zeigen, dass sowohl Unterstützung durch den Ehepartner, als auch individuelle Faktoren wie Optimismus mit einer besseren Adhärenz an die medizinische Behandlung einhergehen. Diesbezüglich zeigte sich eine signifikante Assoziation im Hinblick auf kardiovaskuläre Gesundheit, postoperativen Genesungsverlauf sowie psychischem Wohlbefinden chronisch Kranker. Daher soll untersucht werden, wie Optimismus nierentransplantierter Patienten und der Partner mit der Adhärenz zusammenhängen.


Methodik: Patienten (N=50), die vor mehr als 12 Monaten nach post-mortem Spende eine Niere erhielten, und deren Partner werden in einer Querschnittstudie untersucht. Optimismus wird durch Selbstauskunft (Life-Orientation-Test) von Patient und Partner erhoben. Als Outcome wird die Adhärenz des Patienten an die immunsuppressive Medikation auf Basis von Selbst- und Fremdurteil von Patient und Partner, sowie durch die Berechnung des intra-patient coefficient of variation durch die Blut- Spiegel des Patienten erfasst.


Ergebnisse und Schlussfolgerungen: Die vorläufige Auswertung bei N=46 zeigt, dass höherer Optimismus der Patienten zu einer besseren Adhärenz bezüglich der Wahrnehmung von Kontrollterminen führt (r=.38, p<.01). Optimismus der Partner hängt mit weniger unkontrollierbaren Barrieren (r=.38, p<.01) und weniger Hindernissen insgesamt zusammen. Auch bei nierentransplantierten Patienten und ihren Partnern scheint Optimismus ein wichtiger Faktor für Adhärenz zu sein.



Poster
P97
Familiäre Einflüsse auf die Adhärenz nach Nierentransplantation
*Laura Franke1, Luisa Peters1, Daria Tkachenko1, Mario Schiffer2, Tanja Zimmermann1
1 Medizinische Hochschule Hannover, Klinik für Psychosomatik und Psychotherapie, Hannover, Deutschland
2 Medizinische Hochschule Hannover, Klinik für Nieren- und Hochdruckerkrankungen, Hannover, Deutschland
Abstract-Text :

Einleitung und Fragestellung:


Non-Adhärenz hat eine hohe Prävalenz bei nierentransplantierten (NTx) Patienten. In Studien mit an Schizophrenie oder Essstörung erkrankten Patienten hat sich gezeigt, dass soziale Unterstützung mit besserer Adhärenz an die medizinische Therapie einhergeht und ein negatives emotionales Familienklima zu einem ungünstigen Krankheitsverlauf beiträgt.


Diese Studie untersucht den Einfluss von Partnerschaftsqualität, sozialer Unterstützung und emotionalem Klima in den Familien nierentransplantierter Patienten auf die Adhärenz des Patienten an die immunsuppressive Therapie.


Methoden:


Im Rahmen einer Querschnittuntersuchung wurden N = 50 Patienten (mit NTx vor mehr als 12 Monate, postmortale Spende, Beziehungsdauer mehr als 1 Jahr) und ihre Partner befragt.


Das emotionale Familienklima wurde mit Hilfe des Quality of Marriage Index, dem Fragebogen zur sozialen Unterstützung sowie der Familienklimaskala erfasst. Darüber hinaus wurde die physiologische Erregung des Paares anhand der Sprachgrundfrequenz f0 während eines Paargesprächs objektiv gemessen. Die Adhärenz des Patienten an die immunsuppressive Medikation wurde auf Basis von Selbst- und Fremdurteil von Patient und Partner erfasst.


Ergebnisse und Schlussfolgerungen:


Gegenwärtig sind die Daten von N = 45 Paaren vollständig erhoben. Vorläufige Ergebnisse lassen auf einen negativen Zusammenhang zwischen der selbst eingeschätzten Adhärenz des Patienten und dem Ausmaß an erlebter sozialer Unterstützung schließen. Der Partner als größte soziale und emotionale Stütze sowie die Familie fördern die Adhärenz des Patienten an die immunsuppressive Therapie nach Nierentransplantation.



Poster
P98
Psychische Belastung und gesundheitsbezogene Lebensqualität bei Patient_innen vor Aufnahme auf die Warteliste zur Lebertransplantation
*Angela Buchholz1, Catherine Maschler1, Janka Nölle1, Sylvia  Kröncke1, Martina Sterneck2, Lutz Fischer3,2
1 Universitätsklinikum Hamburg-Eppendorf, Institut und Poliklinik für Medizinische Psychologie, Hamburg, Deutschland
2 Universitätsklinikum Hamburg-Eppendorf, Klinik für Hepatobiliäre Chirurgie und Transplantationschirurgie, Hamburg, Deutschland
3 Universitätsklinikum Hamburg-Eppendorf, , Hamburg, Deutschland
Abstract-Text :

Einleitung und Hintergrund: Am Universitären Transplantations Centrum (UTC) des Universitätsklinikums Hamburg-Eppendorf (UKE) werden alle Patient_innen im Verlauf der Evaluation zur Aufnahme auf die Warteliste für eine Lebertransplantation (LTX) auch psychologisch vorgestellt. Ziel dabei ist nicht nur die Überprüfung der Adhärenz der Betroffenen, sondern auch das frühzeitige Erkennen eines möglichen psychotherapeutischen Interventionsbedarfes. Ziel dieser Untersuchung ist es, die psychische Belastung und Lebensqualität von Patienten vor Aufnahme auf die Warteliste zu erfassen.


Methode: Es wurden alle Patient_innen einbezogen, die im Jahr 2016 im Kontext der LTX-Evaluation ambulant oder stationär psychologisch vorgestellt wurden. Zusätzlich zu einem ca. einstündigen halbstrukturierten Interview erhielten die Patient_innen einen Fragebogen bestehend aus der Short-Form 36-Item Health Survey (SF-36), dem Patient Health Questionnaire (PHQ), und der Posttraumatic Diagnostic Scale (PDS). Patient_innen ohne ausreichende Deutschkenntnisse oder in einem zu schlechten körperlichen Zustand erhielten keinen Fragebogen.


Ergebnisse und Schlussfolgerungen: Insgesamt wurden 132 Patient_innen im Rahmen der LTX-Evaluation psychologisch vorgestellt. Von diesen hatten 71 (53,8%) mindestens eine diagnostizierte psychische Störung in der Vorgeschichte, 16 Patientinnen hatten mehr als eine Diagnose (12,1%). Die häufigsten Diagnosen waren Alkoholabhängigkeit (n = 26; 19,7%) und affektive Erkrankungen (n = 15; 11,3%). Von 65 Patient_innen liegt ein ausgefüllter Fragebogen vor. Eine Einschränkung der Lebensqualität zeigte sich eher im körperlichen (M = 33,2; SD = 12,5) als im psychischen Komponentenscore des SF-36 (M = 46,8; SD = 12,5). Mindestens ein traumatisches Ereignis wurde von 45 Patient_innen berichtet. Zumindest für einen Teil der Patienten besteht ein psychologischer Behandlungsbedarf, für den am UKE spezifische transplantationspsychologische Strukturen entwickelt wurden.