Crossing borders to facilitate live donor kidney transplantation: the Czech-Austrian kidney paired donation program - a retrospective study.

Kidney paired donation (KPD) is a valuable tool to overcome immunological barriers in living donor transplantation. While small national registries encounter difficulties in finding compatible matches, multi-national KPD may be a useful strategy to facilitate transplantation. The Czech (Prague) and Austrian (Vienna) KPD programs, both initiated in 2011, were merged in 2015. A bi-national algorithm allowed for ABO- and low-level HLA antibody-incompatible exchanges, including the option of altruistic donor-initiated domino chains. Between 2011 and 2019, 222 recipients and their incompatible donors were registered. Of those, 95.7% (Prague) and 67.9% (Vienna) entered into KPD registries, and 81 patients received a transplant (95% 3-year graft survival). Inclusion of ABO-incompatible pairs in the Czech program contributed to higher KPD transplant rates (42.6% vs. 23.6% in Austria). After 2015 (11 bi-national match runs), the median pool size increased to 18 pairs, yielding 33 transplants (8 via cross-border exchanges). While matching rates doubled in Austria (from 9.1% to 18.8%), rates decreased in the Czech program, partly due to implementation of more stringent HLA antibody thresholds. Our results demonstrate the feasibility of merging small national KPD programs to increase pool sizes and may encourage the implementation of multi-national registries to expand the full potential of KPD.

Hepatocyte growth on polycapronolactone and 2-hydroxyethylmethacrylate nanofiber sheets enhanced by bone marrow-derived mesenchymal stromal cells.

BACKGROUND/AIMS: The development of hepatocyte-based Bioartificial Liver Assist Devices, intended for the therapy of chronic and fulminant liver failure, is one of the important tasks in the area of tissue engineering. New advances in the development of semipermeable non-woven nanofiber biomaterials and the co-cultivation of bone marrow mesenchymal stromal cells (BMSC) and hepatocytes could be utilized in order to maintain hepatocyte cultures in these devices. METHODOLOGY: We have compared rat hepatocyte growth on nanofiber biomaterials from different polymers, 2-hydroxyethylmethacrylate (HEMA) and ethoxyethylmethacrylate (EOEMA) copolymers, polyurethane (PUR), chitosan and polycapronolactone (PCL) spun from different solvent mixtures. RESULTS: In all cases the adhesion of hepatocytes to nanofibers was significantly better/stronger than to unstructured polymer surfaces; coating the nanofibers with collagen did not increase cell adhesion. We found the best hepatocyte adhesion on HEMA/EOEMA copolymer nanofibers and PCL nanofibers spun from a mixture of ethylacetate and dimethyl sulphoxide. Using a migration assay, we observed the migration of BMSC towards hepatocytes; hepatocytes cocultivated with BMSC excreted lower amounts of stress enzymes. CONCLUSIONS: The results demonstrate that nonwoven nanofiber layers, particularly those containing BMSC, are a suitable biocompatible support for functional hepatocyte cultures and that they can be used in a laboratory bioreactor or potentially in clinical setting.

Cerebral microdialysis reflects the neuroprotective effect of fractionated plasma separation and adsorption in acute liver failure better and earlier than intracranial pressure: a controlled study in pigs.

BACKGROUND: Cerebral edema is a well-recognized and potentially fatal complication of acute liver failure (ALF). The effectiveness of treatments that address intracranial hypertension is generally assessed by measuring intracranial pressure (ICP). The aim of this study was to determine the role of cerebral microdialysis in monitoring the efficacy of fractionated plasma separation and adsorption (FPSA) treatment for ALF. We hypothesized that in ALF cerebral microdialysis reflects the benefits of FPSA treatment on cerebral edema before ICP. METHODS: A surgical resection model of ALF was used in 21 pigs. We measured plasma ammonia concentration, brain concentrations of glucose, lactate, pyruvate, glutamate and glutamine, and ICP. Animals were randomized into three groups: in one group eight animals received 6 hours of FPSA treatment 2 hours after induction of ALF; in another group 10 animals received supportive treatment for ALF only; and in the final group three underwent sham surgery. RESULTS: The ICP was significantly higher in the ALF group than in the FPSA group 9 hours after surgery. The lactate/pyruvate (L/P) ratio was significantly lower in the FPSA group than the ALF group 5 hours after surgery, before any significant difference in ICP was detected. Indeed, significant changes in the L/P ratio could be observed within 1 hour of treatment. Glutamine levels were significantly lower in the FPSA group than the ALF group between 6 hours and 10 hours after surgery. CONCLUSIONS: Brain lactate/pyruvate ratio and concentration of glutamine measured by cerebral microdialysis reflected the beneficial effects of FPSA treatment on cerebral metabolism more precisely and rapidly than ICP in pigs with fulminant ALF. The role of glutamine as a marker of the efficacy of FPSA treatment for ALF appears promising, but needs further evaluation.

Artificial liver support system reduces intracranial pressure more effectively than bioartificial system: an experimental study.

OBJECTIVES: Extracorporeal liver support (ELS) may play a role in bridging therapy in patients with acute liver failure (ALF). The aim of this study was to compare the influence of nonbiological and biological methods on intracranial pressure (ICP) in an animal model of ALF. METHODS: A surgical devascularization model of ALF in pigs (35-40 kg) was used. Elimination therapy started after the onset of hypoglycemia. Biochemical parameters (bilirubin, ammonia, lactate, etc.) as well as ICP and cerebral perfusion pressure (CPP) were monitored for 12 hours. Of the total 31 pigs with ALF, 14 animals were treated by fractionated plasma separation and absorption (FPSA), 10 were treated with a bioartificial liver (BAL), and 7 animals were used as a control group. RESULTS: FPSA and BAL treatment started on average 3 hours 17 minutes and 2 hours 21 minutes, after devascularization and lasted for 5 hours 54 minutes and 5 hours 43 minutes, respectively. Ammonia levels were lower in the FPSA group, and bilirubin levels differed significantly in both the FPSA and BAL groups compared with controls. However, ICP values were reduced more effectively in pigs treated by FPSA: 19.1 vs. 27.0 mm Hg at 9 hours, 22.5 vs. 28.7 mm Hg at 11 hours, and 24.0 vs. 33.0 mm Hg at 12 hours (p<0.05). CONCLUSIONS: The artificial liver support system FPSA reduced ICP values more effectively than the Performer O. Liver RanD BAL system. Compared with this BAL system, the nonbiological elimination method of FPSA is a simpler application with the advantage that it can be applied in a more continuous way.

S-adenosylmethionine does not reduce ischaemia-reperfusion injury to a marginal liver graft in an in vivo experiment.

BACKGROUND/AIMS: There are a limited number of appropriate cadaver liver donors. One possible solution is the use of marginal liver grafts from cadaver donors for liver transplantation. METHODOLOGY: Rats with liver steatosis were divided into four containing seven animals each: I-a: steatotic liver grafts; +S-adenosylmethionine; I-b: steatotic liver grafts were transplanted; no S-adenosylmethionine; II-a: normal liver grafts, +S-adenosylmethionine; II-b: normal liver grafts. Blood samples were taken at days -1, 3 and 14. RESULTS: ALT values at day 14: 1.75 ± 1.10µkat/L (in group I-a), 1.91 ± 1.41µkat/L (in group I-b), 2.13±1.85µkat/L (in group II-a) and 2.08 ± 1.35µkat/L (in group II-b). There were no significant differences between these values. GSH values at day 14 post-transplantation were: 44.90 ± 8.61µM/mg (in group I-a), 43.82±8.58µM/mg (in group I-b), 41.65 ± 4.87µM/mg (in group II-a) and 42.71 ± 4.17µM/mg (in control group II-b). CONCLUSIONS: Our study did not demonstrate the positive effect of S-adenosylmethionine on ischaemia-reperfusion injury during liver transplantation in rats.

Gemcitabine does not prevent acute rejection of the transplanted liver in rats.

Our study was designed to determine effect of gemcitabine on acute rejection of liver in rats. Liver transplantation was performed in rats of the Dark Agouti (DA) and Lewis (LEW) strains. Recipients were divided into three groups: A, DA-to-LEW without immunosuppression; B, DA-to-LEW, treated with cyclosporine A; C, DA-to-LEW, treated with gemcitabine. Immunosuppressants were subcutaneously injected for seven consecutive days after transplantation. On day 7, blood samples and liver graft tissue specimens were harvested. Group A showed severe rejection changes (RAI 8/9); in group B no rejection changes were present (RAI 0/9), and in group C moderate rejection changes were observed (RAI 6/9). Differences were significant between B vs C and A vs C groups; P<0.05. Serum creatinine and urea levels in the gemcitabine group were significantly lower than those in the cyclosporine A group. We did not confirm gemcitabine ability to prevent liver allograft rejection.