BackgroundKidney transplantation (KT) from elderly donors (aged ≥65 years) with acute kidney injury (AKI) remains controversial and these organs might be underutilized. To date, clear evidence supporting the safety of KT from donors with AKI exists solely for younger donor populations. We hypothesized that, when appropriately selected, graft survival and function in recipients of kidneys from AKI and non-AKI donors aged ≥65 years are comparable.MethodsWe conducted a retrospective cohort study analyzing KT outcomes from donors aged ≥65 years with and without AKI that were performed between 2006 and 2021 at three German transplant centers. AKI was defined according to KDIGO criteria. Death-censored graft survival, overall graft survival, patient survival up to 7 years, eGFR up to 5 years as well as incidence of delayed graft function and biopsy proven acute rejection were compared. Kaplan-Meier analyses and multivariable Cox regression were performed.ResultsOf 685 KT recipients, 183 received kidneys from AKI donors, and 502 from non-AKI donors. Most KTs were from donors with KDIGO stage 1 AKI (n = 151; 81.6%). Delayed graft function occurred similarly often in AKI and non-AKI recipients (32.8% vs. 32.8%, p = 1.0). Death-censored graft survival was comparable between AKI and non-AKI groups (7 years: 59.0% vs. 61.3%; p = 0.87). Median eGFR at 12 months was 33.8 mL/min/1.73 m2 (IQR 27.3, 44.2) in the AKI group and 35.5 mL/min/1.73 m2 (IQR 26.3, 44.8) in the non-AKI group (p = 0.79). These results remained unchanged after adjustment for known risk factors of graft survival in the multivariable Cox regression.ConclusionIn this study, KT from ≥65-year-old donors with mostly mild AKI resulted in similar short and long-term graft survival and function compared to KT from ≥65-year-old donors without AKI. These findings support the utilization of AKI kidneys from elderly donors to expand the donor pool without compromising outcomes.

A history of cardiopulmonary resuscitation (CPR) is common in donation after brain death (DBD) donors. While good outcomes have been demonstrated for kidney transplantation (KT) from younger CPR donors (aged typically 18–50 years), it is unclear whether this is true for the growing cohort of ≥65-year-old KT donors. To this end, all KTs from ≥65-year-old DBD donors performed at three German transplant centers from January 2006 to December 2023 (n = 680) were retrospectively analyzed and outcomes of KTs from donors with and without a history of CPR were compared (n = 81 and n = 599, respectively). No significant differences were observed regarding the incidence of delayed graft function (DGF) as well as regarding 1- and 5-year graft function between the CPR and no-CPR groups (DGF: 27.2% vs. 33.1%, p = 0.40; 1-year eGFR (mL/min): 33.3 vs. 35.0, p = 0.75; 5-year eGFR: 35.8 vs. 37.3, p = 0.75, respectively). Death-censored graft survival (73.8% vs. 66.0%, p = 0.24) and patient survival (78.7% vs. 73.5% p = 0.61) were comparable after 5 years between the CPR and no-CPR groups. The results were confirmed by multivariable Cox regression analysis. In conclusion, our results indicate that ≥65-year-old DBD donors with a history of CPR are potentially suitable for KT without impairing allograft outcomes.

BACKGROUND:Simultaneous pancreas-kidney transplantation (SPKT) is the therapy of choice for selected patients with complicated type 1 diabetes mellitus and end-stage renal disease. Pancreas rescue allocation was implemented in Eurotransplant allocation algorithms to increase organ utilization, concurrently facilitating transplantation of supposedly inferior quality organs. The aim of this study was to examine whether outcomes of SPKT after rescue allocation, which can either be recipient-oriented extended allocation or competitive rescue allocation, were as good as after standard allocation. METHODS:This retrospective multicenter analysis of 1504 SPKT performed from 2013 to 2021 evaluated outcomes by allocation type considering survival of patients, pancreas grafts, and kidney grafts. Multivariable analyses further explored the influence of specific donor-, recipient-, and transplant-related variables on outcomes. RESULTS:Multivariable analyses showed no significant differences in SPKT outcome for standard allocation versus either rescue allocation type regarding patient, pancreas graft, and kidney graft survival. Rescue allocation organ donors were older, had higher body mass index, and were more likely to smoke. Rescue allocation had fewer HLA matches. Cold ischemic times of both pancreas and kidneys were longer in competitive rescue allocation but not in recipient-oriented extended allocation. Rescue allocation pancreas recipients had shorter waiting times. Multivariable analyses showed inferior pancreas and kidney graft survival for higher donor age. Higher recipient age correlated with higher mortality despite better pancreas graft survival. CONCLUSIONS:SPKT outcome after rescue allocation is comparable with standard allocation in both patient and graft survival. Age of both donors and recipients essentially influences the success of SPKT.

Zahlreiche Faktoren haben in ihrer Gesamtheit eine komplexe Auswirkung auf das Transplantationsoutcome. Die Allokationsalgorithmen bei Eurotransplant sehen z. B. besondere Punkte bei hoher Dringlichkeit vor, berücksichtigen jedoch beispielsweise nicht den Faktor einer wiederholten Transplantation. Dieser Artikel befasst sich mit den Ergebnissen nach Nieren- und Nieren-Pankreas- Transplantation unter Berücksichtigung der verschiedenen Einflüsse wie wiederholte Retransplantation, Rescue-Allokation und High-Urgency-Allokation.

Prognostic outcome models might help to minimise the discard rates of renal transplants from deceased donors. To this end, we published 2-Step Scores for both delayed graft function and transplant loss with optional histology. With conventional paraffin PAS histology taking at least 3 h excluding transport time, we tested whether fast, mobile confocal histology with portable VivaScope® 2500 systems might offer a viable and more rapid alternative. After omitting 17 biopsies with less than 12 glomeruli and 1 artery, we collected 14 0-h and 16 renal transplant indication (Tx) biopsies for a combined cohort. All biopsies were scanned in less than 10 min with a VivaScope® 2500, rendering pseudo-HE images, and then underwent our regular paraffin work-up. Banff Lesion Scores ct and cv were assessed on the granular ordinal scale and binary as (ct ≤ 1 vs. ct ≥ 2 and cv ≤ 2 vs. cv3) together with the number of glomeruli as used in the previously published 2-Step Scores in a blinded fashion by an expert nephropathologist on the paraffin sections (P) and VivaScope® 2500 scans (V). Additionally, we examined the ratio of globally sclerotic glomeruli. Correlation and mixed effects linear regressions, as well as Fleiss’ kappa statistics, comparing P and V on the combined cohort were applied, supplemented with Bland-Altman statistics providing limits of agreement. Between P and V, granular Banff ct correlated with a kappa of 0.513 (p = 8.38e−05) and a Kendall’s W of 0.706 (p = 0.0694) on the combined cohort; binary Banff ct correlated with a kappa of 0.869 (p = 1.92e−06). We had to exclude two more biopsies in which no artery was found in the scanning plane in V. Granular Banff cv correlated with a kappa of 0.109 (p = 0.345) and a W of 0.677 (p = 0.103) between P and V on the combined cohort and binary Banff cv with a kappa of 0.24 (p = 0.204). The total number of glomeruli correlated between P and V with an R of 0.75 (p = 2.3e−06), the number of globally sclerotic glomeruli with an R of 0.82 (p = 4.1e−08), and the ratio thereof with an R of 0.86 (p = 8.6e−10). Instant, decentralised VivaScope® 2500 histology might deliver Banff ct and the number of glomeruli with sufficient accuracy for the 2-Step Scores to predict the risk of delayed graft function and 1-year death-censored transplant loss in deceased heart-beating donors. In contrast, VivaScope® 2500 assessment of Banff cv might not be accurate enough for use in 2-Step Scores.

BACKGROUND:Pancreatic cystic lesions are common in patients eligible for solid organ transplantation. It has been shown that the need for immunosuppression after organ transplantation increases the rate of malignancies in organ recipients. However, the impact of immunosuppression on pancreatic cystic lesions is yet unknown. AIM:To evaluate the prevalence of pancreatic cystic lesions and the risk of cyst progression in immunosuppressed patients. METHODS:A systematic literature search was performed in relevant databases. Studies reporting either on the prevalence and/or the incidence of pancreatic cyst progression compared to a control group were implemented in the first systematic review and meta-analysis on this topic. RESULTS:The prevalence of pancreatic cystic lesions was comparable with 7% (95%CI: 5%-11%) in the immunosuppressed cohort and 9% (95%CI: 5%-16%) in the control cohort. The mean cyst size increase in the immunosuppression group was 3.2 mm (range 1.0-5.2mm) compared to 3.5 mm (1.0-6.9) in the control group (standardized mean difference 0.0 mm, 95%CI: -0.3-0.2 mm, P = 0.72). There was also no significant increase in the development of resection criteria or worrisome features under immunosuppression either [relative risk 1.1 (fixed effect model), 1.2 (random effects model), P = 0.61]. CONCLUSION:Immunosuppression does not increase the prevalence of pancreatic cystic lesions, nor does it increase the risk of cyst progression in terms of cyst size and development of resection criteria. Therefore, pancreatic cystic lesions in transplant candidates should not be a contraindication for solid organ transplantation.

Here, we retrospectively evaluated the informational yield of 338 post-reperfusion kidney transplant biopsies (including 95 living donations) assessed according to BANFF for the histological characteristics interstitial fibrosis and tubular atrophy (IF/TA), glomerulosclerosis, arteriosclerosis, and acute tubular injury (ATI). Associations with delayed graft function (DGF) and death-censored graft survival were explored through Cox-regression analyses. The maximum follow-up time was 11.4 years, with DGF observed in 108 (32%) cases. After deceased donation there was no association between DGF and histologic parameters. Univariable Cox-regression unveiled an association of IF/TA and glomerulosclerosis with long-term death-censored graft survival (HR per 10% increase: IF/TA 1.63; 95% CI 1.17-2.28; p = 0.003; glomerulosclerosis 1.19; 95% CI 1.01-1.39; p = 0.031). In multivariable Cox regression analyses, adjusted for recognized clinical risk variables like expanded criteria donor-status, donor age, history of diabetes, and HLA-mismatches, only IF/TA maintained association over the total observation period in deceased donations and in the total cohort. Arteriosclerosis and ATI were not associated with clinical outcome after deceased donation. Especially ATI did not affect delayed graft function if only deceased donations were considered. Our data underlines the role of organ quality for transplant outcome prior to acute lesions such as ATI during the transplantation process.

Die Organvergabe, Allokation, erfolgt in Deutschland durch die Internationale Eurotransplant Stiftung mit Sitz im niederländischen Leiden zusammen mit 7 weiteren mitteleuropäischen Ländern. Die Vergabe muss sich hierbei an medizinisch gesicherte Erkenntnisse halten, damit die Transplantationsergebnisse optimiert werden. Darüber hinaus sind jedoch auch ethische Gesichtspunkte zu berücksichtigen und organspezifische Besonderheiten in den Allokationsprozess einzubinden. Die Allokation jedes Organs folgt dabei klar definierten Regeln. Darüber hinaus hat Eurotransplant besondere Regeln für die Vergabe von Organen entwickelt, die von älteren Spendern stammen oder abgelehnt wurden oder aufgrund von medizinischen oder logistischen Begleitumständen nicht direkt vermittelt werden können. Das Ziel der Organallokation ist es, möglichst alle transplantablen Organe rasch und mit anschließend gutem Transplantationsergebnis zu vermitteln.

ZUSAMMENFASSUNGDas Transplantationsgesetz (TPG) bildet die rechtliche Grundlage für die Organ- und Gewebespende. Gegenstand dieser Richtlinie sind die Anforderungen zur Qualitätssicherung in der Transplantationsmedizin. Zur Reduzierung der Risiken und zur Maximierung des Nutzens der Transplantation müssen die Eurotransplant-Mitglied-Staaten ein wirksames System für Qualität und Sicherheit anwenden. Ein Verfahren zur Qualitätssicherung in der Transplantationsmedizin soll Transparenz darüber herstellen, welche Auswirkungen einzelne Schritte im Prozess der Transplantation auf die Behandlungsergebnisse haben. Das international standardisierte Verfahren zur Qualitätssicherung bei Donation begleitet parallel den Entwicklungsprozess der Transplantationsmedizin. Die makroskopische Beurteilung des Spenderorgans durch das Explantationsteam sollte daher als obligate nützliche Ergänzung zu den bisherigen Instrumenten und etablierten Risikofaktoren angesehen und kontinuierlich weiterentwickelt werden.

Background The decision to accept or discard the increasingly rare and marginal brain-dead donor kidneys in Eurotransplant (ET) countries has to be made without solid evidence. Thus, we developed and validated flexible clinicopathological scores called 2-Step Scores for the prognosis of delayed graft function (DGF) and 1-year death-censored transplant loss (1y-tl) reflecting the current practice of six ET countries including Croatia and Belgium.Methods The training set was n = 620 for DGF and n = 711 for 1y-tl, with validation sets n = 158 and n = 162, respectively. In Step 1, stepwise logistic regression models including only clinical predictors were used to estimate the risks. In Step 2, risk estimates were updated for statistically relevant intermediate risk percentiles with nephropathology.Results Step 1 revealed an increased risk of DGF with increased cold ischaemia time (CIT), donor and recipient body mass index, dialysis vintage, number of HLA-DR mismatches or recipient cytomegalovirus immunoglobulin G positivity. On the training and validation set, c-statistics were 0.672 and 0.704, respectively. At a range between 18% and 36%, accuracy of DGF-prognostication improved with nephropathology including number of glomeruli and Banff cv (updated overall c-statistics of 0.696 and 0.701, respectively). Risk of 1y-tl increased in recipients with CIT, sum of HLA-A, -B, -DR mismatches, and donor age. On training and validation sets, c-statistics were 0.700 and 0.769, respectively. Accuracy of 1y-tl prediction improved (c-statistics = 0.706 and 0.765) with Banff ct. Overall, calibration was good on the training, but moderate on the validation set; discrimination was at least as good as established scores when applied to the validation set.Conclusion Our flexible 2-Step Scores with optional inclusion of time-consuming and often unavailable nephropathology should yield good results for clinical practice in ET, and may be superior to established scores. Our scores are adaptable to donation after cardiac death and perfusion pump use.

ZUSAMMENFASSUNGDie postmortale Organspende und die Vermittlung von Organen berühren fundamentale medizinische, ethische und rechtliche Facetten des gesellschaftlichen Zusammenlebens. Die Nierentransplantation stellt heute – mehr als ein halbes Jahrhundert nach ihrer Einführung in die klinische Behandlung – ein etabliertes und sicheres Therapieverfahren mit guten Langzeitergebnissen dar. Der langfristige Erfolg einer Transplantation ist multifaktoriell bedingt und hängt entscheidend von der dauerhaften und gewissenhaften Einnahme der Immunsuppressiva ab. Die optimale immunsuppressive Therapie sichert langfristig die Funktion der transplantierten Organe, indem sie die akute Transplantatabstoßung und eine chronische Transplantatdysfunktion verhindert. Die individualisierte Immunsuppression und qualifizierte Nachsorge können entscheidend dazu beitragen, die Funktionalität des Transplantats und seine Überlebenszeit relevant zu verlängern.

Background. For patients with complicated type 1 diabetes having, for example, hypoglycemia unawareness and end-stage renal disease because of diabetic nephropathy, combined pancreas and kidney transplantation (PKT) is the therapy of choice. However, the shortage of available grafts and complex impact of risk factors call for individualized, impartial predictions of PKT and pancreas transplantation (PT) outcomes to support physicians in graft acceptance decisions. Methods. Based on a large European cohort with 3060 PKT and PT performed between 2006 and 2021, the 3 primary patient outcomes time to patient mortality, pancreas graft loss, and kidney graft loss were visualized using Kaplan-Meier survival curves. Multivariable Cox proportional hazards models were developed for 5- and 10-y prediction of outcomes based on 26 risk factors. Results. Risk factors associated with increased mortality included previous kidney transplants, rescue allocations, longer waiting times, and simultaneous transplants of other organs. Increased pancreas graft loss was positively associated with higher recipient body mass index and donor age and negatively associated with simultaneous transplants of kidneys and other organs. Donor age was also associated with increased kidney graft losses. The multivariable Cox models reported median C-index values were 63% for patient mortality, 62% for pancreas loss, and 55% for kidney loss. Conclusions. This study provides an online risk tool at https://riskcalc.org/ptop for individual 5- and 10-y post-PKT and PT patient outcomes based on parameters available at the time of graft offer to support critical organ acceptance decisions and encourage external validation in independent populations.

ZUSAMMENFASSUNG Pathophysiologisch lassen sich neben der T-zellulären und der antikörpervermittelten (humoralen) Abstoßung gegen humane Leukozytenantigene (HLA) auch Abstoßungen gegen Nicht-HLA-Moleküle, komplementgetriggerte Abstoßungen und Abstoßungen durch Missing-Self beschreiben. Klinisch müssen in Abhängigkeit vom Zeitpunkt nach einer Transplantation immer auch nichtimmunologische Ursachen einer Transplantatdysfunktion in Betrachtung gezogen werden. Trotz moderner immunsuppressiver Medikation ist die chronische Nierentransplantatabstoßung der limitierende Faktor für das Überleben eines Nierentransplantats. Akute Abstoßungen lassen sich nur in Zusammenschau von klinischen, labormedizinischen und apparativen Befunden nachweisen – der Goldstandard in der Diagnostik einer Abstoßung stellt die nephropathologische Begutachtung eines Nierenbiopsie-Stanzzylinders dar. Die Nierentransplantatbiopsie ist ein standardisiertes, und in geübten Händen für Patienten und Transplantat sicheres, diagnostisches Verfahren.

The major problem in diagnosing pancreatic carcinoma is the lack of disease-specific early symptoms, the more so because symptoms that potentially indicate malignant disease can be hard to distinguish from nonspecific ones. Pancreatic cancer therefore frequently emerges at an advanced stage. Numerous tumor-associated parameters have an impact on the clinical appearance of affected patients. Besides impaired exocrine and endocrine pancreatic functions, which consecutively result in digestive disorders and diabetes, the tumor invasion into intrapancreatic and extrapancreatic nerval plexus results in progressive pain. Furthermore, tumor invasion into adjacent organs causes intestinal obstruction and jaundice. In contrast with pancreatic cancer, neuroendocrine tumors of the pancreas characteristically prompt more specific symptoms, if hormonally active. These will be briefly outlined in this context. In addition to the clinical symptoms, this chapter reports on identified risk factors of pancreatic cancer.

Background. Whenever the kidney standard allocation (SA) algorithms according to the Eurotransplant (ET) Kidney Allocation System or the Eurotransplant Senior Program fail, rescue allocation (RA) is initiated. There are 2 procedurally different modes of RA: recipient oriented extended allocation (REAL) and competitive rescue allocation (CRA). The objective of this study was to evaluate the association of patient survival and graft failure with RA mode and whether or not it varied across the different ET countries. Methods. The ET database was retrospectively analyzed for donor and recipient clinical and demographic characteristics in association with graft outcomes of deceased donor renal transplantation (DDRT) across all ET countries and centers from 2014 to 2021 using Cox proportional hazards methods. Results. Seventeen thousand six hundred seventy-nine renal transplantations were included (SA 15 658 [89%], REAL 860 [4.9%], and CRA 1161 [6.6%]). In CRA, donors were older, cold ischemia times were longer, and HLA matches were worse in comparison with REAL and especially SA. Multivariable analyses showed comparable graft and recipient survival between SA and REAL; however, CRA was associated with shorter graft survival. Germany performed 76% of all DDRTs after REAL and CRA and the latter mode reduced waiting times by up to 2.9 y. Conclusions. REAL and CRA are used differently in the ET countries according to national donor rates. Both RA schemes optimize graft utilization, lead to acceptable outcomes, and help to stabilize national DDRT programs, especially in Germany.

Renal ischemia-reperfusion injury (IRI) is associated with reduced allograft survival, and each additional hour of cold ischemia time increases the risk of graft failure and mortality following renal transplantation. Receptor-interacting protein kinase 3 (RIPK3) is a key effector of necroptosis, a regulated form of cell death. Here, we evaluate the first-in-human RIPK3 expression dataset following IRI in kidney transplantation. The primary analysis included 374 baseline biopsy samples obtained from renal allografts 10 minutes after onset of reperfusion. RIPK3 was primarily detected in proximal tubular cells and distal tubular cells, both of which are affected by IRI. Time-to-event analysis revealed that high RIPK3 expression is associated with a significantly higher risk of one-year transplant failure and prognostic for one-year (death-censored) transplant failure independent of donor and recipient associated risk factors in multivariable analyses. The RIPK3 score also correlated with deceased donation, cold ischemia time and the extent of tubular injury.

Nowadays, benign tumors of the papilla, less than 2cm in size, can usually be extirpated endoscopically. However, the operative approach remains the therapy of choice in those cases with extended or malignant lesions of the ampulla. Surgical therapy for tumors of the papilla or ampulla is a crucial component in the patient's treatment, providing a locally excisional procedure (ampullectomy) and an oncologically resective procedure (partial pancreatoduodenectomy). Besides the technical feasibility and therefore resectability of the tumor, it is of major importance to evaluate the operative radicality when diagnostics are completed. This approach takes the existing medical data into account, guarantees sustainable outcomes, and improves long-term patient survival. This chapter presents operative strategies and their long-term outcomes.