| 1. |
- Bucin, Dragan, et al.
(författare)
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Heart transplantation across the antibodies against HLA and ABO
- 2006
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Ingår i: Transplant International. - : Frontiers Media SA. - 1432-2277 .- 0934-0874. ; 19:3, s. 239-244
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Tidskriftsartikel (refereegranskat)abstract
- We have intentionally performed heart transplantation in a 5-year-old child, despite the most unfavourable risk factors for patient survival; the presence of high level of antibodies against donor's human leucocyte antigen (HLA) class I/II and blood group antigens. Pretransplant treatment by mycophenolate mofetil, prednisolone, tacrolimus, intravenous immunoglobulin, rituximab, protein-A immunoadsorption (IA) and plasma exchange reduced antibody titres against the donor's lymphocytes from 128 to 16 and against the donor's blood group antigen from 256 to 0. The patient was urgently transplanted with a heart from an ABO incompatible donor (A(1) to O). A standard triple-drug immunosuppressive protocol was used. No hyperacute rejection was seen. Antibodies against the donor's HLA antigens remained at a low level despite three acute rejections. Rising anti-A(1) blood group antibodies preceded the second rejection and were reduced by two blood group-specific IAs and remained at a low level. The patient is doing well despite the persistence of donor-reactive antibodies.
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| 2. |
- Demirbas, Alper, et al.
(författare)
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Low toxicity regimens in renal transplantation: a country subset analysis of the Symphony study
- 2009
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Ingår i: Transplant International. - : Frontiers Media SA. - 1432-2277 .- 0934-0874. ; 22:12, s. 1172-1181
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Tidskriftsartikel (refereegranskat)abstract
- P>Regional transplant practices may affect clinical outcomes within multinational studies. This study evaluated whether the overall results from the Symphony study can be generalized to the participating countries. De novo adult renal transplant recipients (n = 1645) were randomized to receive standard-dose cyclosporine, or daclizumab induction plus low-dose cyclosporine, low-dose tacrolimus, or low-dose sirolimus, all in addition to mycophenolate mofetil and steroids. Data for the highest patient-recruiting countries, Spain (n = 275), Germany (n = 316) and Turkey (n = 258), were compared. Patient transplant characteristics were different among the country subsets; only deceased donors in Spain, more expanded criteria donors in Germany, and mainly living donors in Turkey. Efficacy results for the three countries were consistent with that of the overall study - renal function and biopsy-proven acute rejection (BPAR) rates were superior with low-dose tacrolimus. Turkey had higher mean calculated glomerular filtration rate across all treatment groups (60.6-72.2 ml/min) compared with that of Spain (51.1-57.5 ml/min) and Germany (51.3-62.9 ml/min). Spain and Turkey had lower BPAR rates across the four treatment groups compared with the overall study; Germany had much higher rates (21.0-54.2%). These findings confirm the general applicability of the Symphony study results and highlight the importance of inclusion of patients from different geographic origins in randomized clinical trials.
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| 3. |
- Ekberg, Henrik, et al.
(författare)
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Challenges and considerations in diagnosing the kidney disease in deteriorating graft function.
- 2012
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - : Frontiers Media SA. - 1432-2277. ; 25:11, s. 1119-1128
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Tidskriftsartikel (refereegranskat)abstract
- Despite significant reductions in acute-rejection rates with the introduction of calcineurin inhibitor (CNI)-based immunosuppressive therapy, improvements in long-term graft survival in renal transplantation have been mixed. Improving long-term graft survival continues to present a major challenge in the management of kidney-transplant patients. CNIs are a key component of immunosuppressive therapy, and chronic CNI toxicity has been widely thought to be a major factor in late graft failure. However, recent studies examining the causes of late graft failure in detail have challenged this view, highlighting the importance of antibody-mediated rejection and other factors. In addition, the diagnosis of CNI nephrotoxicity represents a challenge to clinicians, with the potential for over-diagnosis and an inappropriate reduction in immunosuppressive therapy. When graft function is deteriorating, accurately determining the cause of the kidney disease is essential for effective long-term management of the patient. Diagnosis requires a thorough clinical investigation, and in the majority of cases a specific cause can be identified.
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| 4. |
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| 5. |
- Elinder, Carl-Gustaf, et al.
(författare)
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Variations in graft and patient survival after kidney transplantation in Sweden: caveats in interpretation of center effects when benchmarking.
- 2009
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - : Frontiers Media SA. - 1432-2277 .- 0934-0874. ; 22:11, s. 1051-7
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Tidskriftsartikel (refereegranskat)abstract
- Benchmarking and comparisons between transplantation centers are becoming more common. A crude comparison indicated a 50% difference in patient survival between centers in Sweden. A 'task group' was formed to refute or confirm and learn from this observation. Patient survival and graft survival of 5 933 patients transplanted at three different transplantation centers in Sweden (Stockholm, Göteborg, and Malmö) were followed up until February 2007. Patient survival and graft survival were compared between the centers with and without consideration being given to important covariates such as time period, type of donation (living or deceased donor), gender, and age. A refined cohort of 2,956 adult patients that had been transplanted for the first time between 1991 and 2007 was assessed in more detail using Cox regression analysis. The difference in patient and transplant outcome observed in the crude comparison diminished considerably after adjustment for differences in case mix and time period of transplantation, and was neither evident nor significant after 1999. Patient survival and graft survival have improved considerably during the time period since 1991. The adjusted hazards ratio for mortality was 0.39 (95% CI 0.29-0.53) for patients who were transplanted after 1999 when compared with those transplanted between 1991 and 1994. Crude comparisons between results from transplantation centers may be severely confounded not only by case mix but also by differences in the proportion of patients transplanted during different time periods. Patient outcome and graft outcome have improved considerably since 1991, and after 1999 center effects were no longer apparent in Sweden.
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| 6. |
- Grinyo, Josep, et al.
(författare)
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Association of four DNA polymorphisms with acute rejection after kidney transplantation
- 2008
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Ingår i: Transplant International. - : Frontiers Media SA. - 1432-2277 .- 0934-0874. ; 21:9, s. 879-891
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Tidskriftsartikel (refereegranskat)abstract
- Renal transplant outcomes exhibit large inter-individual variability, possibly on account of genetic variation in immune-response mediators and genes influencing the pharmacodynamics/pharmacokinetics of immunosuppressants. We examined 21 polymorphisms from 10 genes in 237 de novo renal transplant recipients participating in an open-label, multicenter study [Cyclosporine Avoidance Eliminates Serious Adverse Renal-toxicity (CAESAR)] investigating renal function and biopsy-proven acute rejection (BPAR) with different cyclosporine A regimens and mycophenolate mofetil. Genes were selected for their immune response and pharmacodynamic/pharmacokinetic relevance and were tested for association with BPAR. Four polymorphisms were significantly associated with BPAR. The ABCB1 2677T allele tripled the odds of developing BPAR (OR: 3.16, 95% CI [1.50-6.67]; P = 0.003), as did the presence of at least one IMPDH2 3757C allele (OR: 3.39, 95% CI [1.42-8.09]; P = 0.006). BPAR was almost fivefold more likely in patients homozygous for IL-10 -592A (OR: 4.71, 95% CI [1.52-14.55]; P = 0.007) and twice as likely in patients with at least one A allele of TNF-alpha G-308A (OR: 2.18, 95% CI [1.08-4.41]; P = 0.029). There were no statistically significant interactions between polymorphisms, or the different treatment regimens. Variation in genes of immune response and pharmacodynamic/pharmacokinetic relevance may be important in understanding acute rejection after renal transplant.
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| 7. |
- Paul, Clara, et al.
(författare)
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Immunosuppressive properties of a series of novel inhibitors of the monocarboxylate transporter MCT-1.
- 2012
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - : Frontiers Media SA. - 1432-2277.
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Tidskriftsartikel (refereegranskat)abstract
- We have recently described the immunosuppressive properties of AR-C117977 and AR-C122982, representatives of a group of compounds identified as inhibitors of lactate transporters (monocarboxylate transporters; MCTs). These compounds demonstrate the potential therapeutic usefulness of inhibiting MCT-1, but their physical and metabolic properties made them unsuitable for further development. We have therefore tried to find analogues with similar immunosuppressive efficacy and a more suitable profile for oral administration. Five analogues of AR-C117977 were synthesised and screened for binding to the transporter, for inhibition of proliferation of both human and rat lymphocytes, for in vivo activity in a model of graft-versus-host (GvH) response in the rat, and in high- and low-responder cardiac transplant models in the rat. There was a good correlation between levels of binding of the five analogues to MCT and their inhibition of lymphocyte proliferation in human and rat cells. Furthermore, activity in both the GvH response and the cardiac transplant models correlated well with the determined concentrations of test compound in plasma. These findings on new analogues of MCT-1 inhibitors have taken us further towards defining the pharmacokinetic properties that may help to identify future drug candidates among inhibitors of MCT-1.
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| 8. |
- Xia, Junjie, et al.
(författare)
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Suppressing memory T cell activation induces islet allograft tolerance in alloantigen-primed mice
- 2010
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Ingår i: Transplant International. - : Frontiers Media SA. - 1432-2277 .- 0934-0874. ; 23:11, s. 1154-1163
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Tidskriftsartikel (refereegranskat)abstract
- P>Memory T cells are known to play a key role in prevention of allograft tolerance in alloantigen-primed mice. Here, we used an adoptively transferred memory T cell model and an alloantigen-primed model to evaluate the abilities of different combinations of monoclonal antibodies (mAb) to block key signaling pathways involved in activation of effector and memory T cells. In the adoptively transferred model, the use of anti-CD134L mAb effectively prevented activation of CD4+ memory T cells and significantly prolonged islet survival, similar to the action of anti-CD122 mAb to CD8+ memory T cells. In the alloantigen-primed model, use of anti-CD134L and anti-CD122 mAbs in addition to co-stimulatory blockade with anti-CD154 and anti-LFA-1 prolonged secondary allograft survival and significantly reduced the proportion of memory T cells; meanwhile, this combination therapy increased the proportion of regulatory T cells (Tregs) in the spleen, inhibited lymphocyte infiltration in the graft, and suppressed alloresponse of recipient splenic T cells. However, we also detected high levels of alloantibodies in the serum which caused high levels of damage to the allogeneic spleen cells. Our results suggest that combination of four mAbs can significantly suppress the function of memory T cells and prolong allograft survival in alloantigen primed animals.
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| 9. |
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| 10. |
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| 11. |
- Biglarnia, Ali-Reza, et al.
(författare)
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Prompt reversal of a severe complement activation by eculizumab in a patient undergoing intentional ABO-incompatible pancreas and kidney transplantation
- 2011
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 24:8, s. e61-e66
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Tidskriftsartikel (refereegranskat)abstract
- We describe the presumably first intentional ABO-incompatible deceased-donor kidney and pancreas transplantation with a severe antibody-mediated rejection during a rebound of isoagglutinins. Rejection was successfully treated with eculizumab, which inhibits the terminal pathway of complement. Complement analysis (C3, C3d,g, and a modified assay of classical complement-related hemolytic function) documented complement activation and confirmed that eculizumab completely blocked complement function. At 6 months, the patient had normal kidney and pancreas function, and histological evaluations revealed no evidence of sustained graft damage. This successful transplantation suggests that ABO barriers can safely be overcome without extensive preconditioning, when the complement inhibitor eculizumab is included.
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| 12. |
- Bjøro, K, et al.
(författare)
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Liver transplantation in patients over 60 years of age
- 2000
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 13:Suppl 1, s. S165-S170
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Tidskriftsartikel (refereegranskat)abstract
- Liver transplantation was previously only offered to patients under 60 years of age. We have analyzed the outcome after acceptance on the waiting list and after liver transplantation of patients over 60 years old. A total of 150 patients over 60 years old were listed for a first liver transplantation during 1990-1998. The annual number increased throughout the period. Primary biliary cirrhosis, primary sclerosing cholangitis, and acute hepatic failure were the most frequent diagnoses. A total of 119 patients received a first liver allograft. The patient 1-year survival was 75% and 3-year survival 62%, which was not significantly lower (P = 0.21) than that of the younger patients. When correcting for year of transplantation, the survival was, however, moderately but significantly lower than among the younger patients. Survival among those > 65 years (n = 38) did not differ from that of patients 60-65 years of age (n = 81). We conclude that an increasing number of patients over 60 years old can be listed for liver transplantation and receive a liver allograft with highly satisfying results.
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| 13. |
- Brandhorst, Heide, 1962-, et al.
(författare)
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Perfluorohexyloctane improves long-term storage of rat pancreata for subsequent islet isolation
- 2009
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 22:10, s. 1017-1022
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Tidskriftsartikel (refereegranskat)abstract
- Pancreas oxygenation by means of the hyperoxygen carrier perfluorodecalin (PFD) has been established to prevent ischemically induced damage from cold-stored pancreata. However, large-scale studies did not confirm the promising results that had been observed in smaller donor populations. This study assessed whether islet isolation from pancreata stored for prolonged periods can be improved by utilizing the new oxygen carrier perfluorohexyloctane (F6H8) characterized by lower gravity and higher lipophilicity than PFD. Subsequent to 24 h of storage in either oxygenated PFD or F6H8, the rat pancreata were assessed for the intrapancreatic partial oxygen pressure (pO(2)) and subsequently processed with current standard procedures. The intrapancreatic pO(2) was nearly identical in rat pancreata stored either in PFD or F6H8. Nevertheless, rat islet isolation outcome was significantly increased in terms of yield, integrity, in vitro function and post-transplant outcome after transplantation in diabetic nude mice when F6H8 was used as oxygen carrier. This proof-of-concept study demonstrated in rats that islet isolation performed after long-term storage of oxygenated pancreatic tissue can be significantly improved if PFD was replaced by F6H8.
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| 14. |
- Chapman, Jeremy, et al.
(författare)
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Follow-up after renal transplantation with organs from donors after cardiac death
- 2006
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 19:9, s. 715-719
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Tidskriftsartikel (refereegranskat)abstract
- Kidneys obtained from donors after cardiac death (DCD) are known to have higher rates of primary nonfunction and delayed graft function (DGF) than heart beating cadaveric donor (CAD) kidneys, but little is known about long-term function of DCD grafts that survive to 1 year. To investigate the outcomes of renal transplant recipients whose DCD graft functioned for at least 1 year, this study analyzed data collected from 326 DCD graft recipients and 340 CAD-matched controls enrolled in a prospective, multinational, observational study - Neoral (R)-MOST (Multinational Observational Study in Transplantation) (Novartis, Basel, Switzerland). No differences were found in the demographics or immunosuppression between the two groups. All patients received a Neoral (R)-based immunosuppressive regimen. Donors after cardiac death graft recipients had a higher incidence of DGF (40% vs. 27% CAD; P < 0.001). One year glomerular filtration rate (GFR) and GFR-decline after 1 year were similar in DCD and CAD recipients (GFR 56 ml/min DCD vs. 59 ml/min CAD; GFR-decline -1.3 ml/min DCD vs. -1.4 ml/min CAD; P = not significant). Multifactorial analyses confirmed that GFR at 1 year was significantly influenced by donor age and gender, DGF, and acute rejection; however, DCD status was not an independent risk factor in cyclosporine-treated patients with grafts that had functioned for at least 1 year.
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| 15. |
- Felldin, Marie, et al.
(författare)
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The antibody response to pandemic H1N1 2009 influenza vaccine in adult organ transplant patients.
- 2012
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - : Frontiers Media SA. - 1432-2277. ; 25:2, s. 166-71
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Tidskriftsartikel (refereegranskat)abstract
- Limited data are available regarding antibody response and the safety of the monovalent influenza A H1N1/09 vaccine for immunocompromised patients. In this study, the humoral response to this vaccine in solid organ transplant (SOT) recipients and healthy individuals was evaluated. Eighty-two SOT recipients and 28 healthy individuals received two doses of the influenza A H1N1/09 AS03 adjuvanted vaccine containing 3.75mg of haemagglutinin at a 3- to 4-week interval. Serum samples were drawn at baseline and 3-4weeks after the first and second vaccine doses. Seroprotective titres were measured with a haemagglutination inhibition. After the first dose seroprotective titres were observed in 69% of the SOT patients and in 96% of the healthy controls (P=0.006), and increased after the second dose to 80% and 100%, respectively (P=0.003). All controls and 77% of the SOT recipients achieved a ≥4-fold titre rise after the first immunisation (P=0.005). The vaccine was well tolerated and no acute rejection was observed. Influenza A H1N1/09 vaccine elicited a protective antibody response in the majority of SOT recipients, but the response was lower when compared with controls. A second dose significantly improved vaccine immunogenicity in SOT recipients. (ClinicalTrials.gov number: NCT01254955).
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| 16. |
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| 17. |
- Kakabadze, Zurab, et al.
(författare)
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Long-term engraftment and function of transplanted pancreatic islets in vascularized segments of small intestine
- 2011
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 24:2, s. 175-183
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Tidskriftsartikel (refereegranskat)abstract
- This study evaluated the potential of vascularized small intestinal segments for pancreatic islet transplantation. Islets isolated from Lewis rats were transplanted into diabetic syngeneic recipients. Segments of small intestine were prepared by denudation of the mucosal layer prior to implantation of pancreatic islets into the segments. Animal groups were established to determine engraftment, survival and function of islets transplanted into either intestinal segments or portal vein over up to 60 days. We found transplantation of functionally intact pancreatic islets into small intestinal segments was well tolerated. Transplanted islets were rapidly engrafted in intestinal segments as demonstrated vascularization and expression of insulin and glucagon throughout the 60-day duration of the studies. Transplantation of islets restored euglycemia in diabetic rats, which was similar to animals receiving islets intraportally. Moreover, animals treated with islet transplants showed normal responses to glucose challenges. Removal of graft-bearing intestinal segments led to recurrence of hyperglycemia indicating that transplanted islets were responsible for improved outcomes. Therefore, we concluded that vascularized intestinal segments supported reorganization, survival and function of transplanted islets with therapeutic efficacy in streptozotocin-treated diabetic rats. The approach described here will be appropriate for studying islet biogenesis, reorganization and function, including for cell therapy applications.
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| 18. |
- Lund, Tormod, et al.
(författare)
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Glucocorticoids reduce pro-inflammatory cytokines and tissue factor in vitro and improve function of transplanted human islets in vivo
- 2008
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 21:7, s. 669-678
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Tidskriftsartikel (refereegranskat)abstract
- Factors that upregulate the inflammatory status of islets probably contribute to detrimental processes leading to islet loss and impaired post-transplant function. Glucocorticoids have the potential to counteract inflammation and thus improve islet quality and function. However, glucocorticoids have diabetogenic properties and are known to hamper islet function in vivo. We examined the effect of glucocorticoids on human islets in vitro and in vivo after 48 h of exposure to different concentrations of methylprednisolone. Protein and/or mRNA levels of insulin, interleukin (IL)-8, macrophage chemoattractant protein (MCP)-1, tissue factor (TF), and IL-10 were assessed by enzyme immunosorbent assay and real time quantitative reverse transcription-polymerase chain reaction. Viability was assessed with fluorescein diacetate-propidium iodide staining, adenosine triphosphate (ATP) content and caspase activity. Six-hundred islet equivalents (IEQ) were transplanted to severe combined immunodeficiency disease mice and graft function assessed by glucose measurements and intraperitoneal glucose tolerance tests. Glucocorticoids reduce mRNA and protein levels of TF, MCP-1 and IL-8, and enhance ATP content. Insulin secretion was initially inhibited; however, after 7 days in culture, it was superior to controls. Islets exposed to methylprednisolone cured diabetic mice more effectively than control islets. In conclusion, glucocorticoids have potent anti-inflammatory properties on human islets without permanent effects on insulin metabolism. Brief glucocorticoid exposure improves function of transplanted human islets in vivo.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Rissler, P., et al.
(författare)
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Adriamycin cytotoxicity may stimulate growth of hepatocellular tumours in an experimental model for adjuvant systemic chemotherapy in liver transplantation
- 2005
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 18:8, s. 992-1000
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Tidskriftsartikel (refereegranskat)abstract
- Adjuvant treatment with adriamycin has been suggested to improve results after liver transplantation for hepatocellular cancer. Here we have applied an animal model for evaluation of treatment with adriamycin and/or cyclosporine A on liver tumour growth. Three chemically induced rat liver tumours with various degree of differentiation were transferred to the spleens of syngenic rats. Each recipient group was divided into four subgroups, treated with adriamycin and/or cyclosporine A or none of the drugs. When the tumour was well differentiated no proliferation was found in any of the subgroups. When the tumour exhibited a more pronounced dysplasia, adriamycin stimulated tumour growth. This effect was further increased by cyclosporine. In the animals transplanted with the most aggressive tumour, adriamycin inhibited tumour growth. When given together with cyclosporine this inhibition was counteracted. These data suggest that adriamycin, especially when given together with cyclosporine, may have a stimulatory effect on liver tumour cell growth.
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| 23. |
- van Keimpema, Loes, et al.
(författare)
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Excellent survival after liver transplantation for isolated polycystic liver disease: an European Liver Transplant Registry study.
- 2011
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - : Frontiers Media SA. - 1432-2277. ; 24:12, s. 1239-45
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Tidskriftsartikel (refereegranskat)abstract
- Patients with end-stage isolated polycystic liver disease (PCLD) suffer from incapacitating symptoms because of very large liver volumes. Liver transplantation (LT) is the only curative option. This study assesses the feasibility of LT in PCLD. We used the European Liver Transplant Registry (ELTR) database to extract demographics and outcomes of 58 PCLD patients. We used Kaplan-Meier survival analysis for survival rates. Severe abdominal pain (75%) was the most prominent symptom, while portal hypertension (35%) was the most common complication in PCLD. The explantation of the polycystic liver was extremely difficult in 38% of patients, because of presence of adhesions from prior therapy (17%). Karnofsky score following LT was 90%. The 1- and 5-year graft survival rate was 94.3% and 87.5%, while patient survival rate was 94.8% and 92.3%, respectively. Survival rates after LT for PCLD are good.
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| 24. |
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| 25. |
- Wahlin, Staffan, et al.
(författare)
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Combined liver and kidney transplantation in acute intermittent porphyria
- 2010
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 23:6, s. e18-e21
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Tidskriftsartikel (refereegranskat)abstract
- We report two patients with acute intermittent porphyria (AIP) who were successfully treated with combined liver and kidney transplantation. Both had a very poor quality of life as a result of years of frequent acute porphyria symptoms, chronic peripheral neuropathy and renal failure requiring dialysis. After transplantation, clinical and biochemical signs of porphyria disappeared. The excretion pattern of porphyrin precursors normalized within the first day and plasma porphyrins returned to normal within a week. These and other recent cases have clarified previous concerns and have helped to formulate the indications for and the timing of transplantation in AIP.
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| 26. |
- Biglarnia, Ali-Reza, et al.
(författare)
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Prompt reversal of a severe complement activation by eculizumab in a patient undergoing intentional ABO-incompatible pancreas and kidney transplantation
- 2011
-
Ingår i: Transplant International. - : John Wiley & Sons. - 0934-0874 .- 1432-2277. ; 24:8, s. e61-e66
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Tidskriftsartikel (refereegranskat)abstract
- We describe the presumably first intentional ABO-incompatible deceased-donor kidney and pancreas transplantation with a severe antibody-mediated rejection during a rebound of isoagglutinins. Rejection was successfully treated with eculizumab, which inhibits the terminal pathway of complement. Complement analysis (C3, C3d,g, and a modified assay of classical complement-related hemolytic function) documented complement activation and confirmed that eculizumab completely blocked complement function. At 6 months, the patient had normal kidney and pancreas function, and histological evaluations revealed no evidence of sustained graft damage. This successful transplantation suggests that ABO barriers can safely be overcome without extensive preconditioning, when the complement inhibitor eculizumab is included.
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| 27. |
- Campistol, Josep M, et al.
(författare)
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Practical recommendations for the early use of m-TOR inhibitors (sirolimus) in renal transplantation.
- 2009
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - : Frontiers Media SA. - 1432-2277. ; 22:7, s. 681-7
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Tidskriftsartikel (refereegranskat)abstract
- m-TOR inhibitors (e.g. sirolimus) are well-tolerated immunosuppressants used in renal transplantation for prophylaxis of organ rejection, and are associated with long-term graft survival. Early use of sirolimus is often advocated by clinicians, but this may be associated with a number of side-effects including impaired wound-healing, lymphoceles and delayed graft function. As transplant clinicians with experience in the use of sirolimus, we believe such side-effects can be limited by tailored clinical management. We present recommendations based on published literature and our clinical experience. Furthermore, guidance is provided on sirolimus use during surgery, both at transplantation and for subsequent operations.
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| 28. |
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| 29. |
- Friend, Peter, et al.
(författare)
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Incidence of anemia in sirolimus-treated renal transplant recipients : the importance of preserving renal function
- 2007
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 20:9, s. 754-760
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Tidskriftsartikel (refereegranskat)abstract
- Sirolimus (SRL) has a concentration-related effect on hematopoiesis. In this study, 430 renal transplant recipients were randomized (1:1) 3 months post-transplantation to continue SRL-cyclosporine (CsA)-steroids (ST) or to have CsA withdrawn (SRL-ST). Over 5 years, on therapy calculated glomerular filtration rate (GFR), hematological indices, erythropoietin (EPO) use, and rates of mild, moderate, and severe anemia were determined. Longitudinal analyses using linear mixed models examined covariates predicting hemoglobin (Hgb) levels. Mean Hgb was significantly lower with SRL-ST at 6 months; but subsequently became significantly higher (at 2 years, 129 vs. 135 g/l, SRL-CsA-ST vs. SRL-ST, P<0.001). Mean corpuscular volume was low with both therapies, and significantly lower with SRL-ST. EPO use was similar in the two groups, approximately 30% during the first year and 10% thereafter. The incidence of anemia was significantly higher with SRL-CsA-ST>or=2 years. At year 5, only 39.1% of SRL-CsA-ST patients had normal Hgb vs. 68.5% of SRL-ST patients. GFR and recipient age as well as the interaction term x treatment time were significant covariates predicting Hgb. CsA withdrawal followed by SRL immunotherapy resulted in significantly less anemia than SRL-CsA-ST, despite twofold higher SRL exposure. This suggests that the improvement in GFR accompanying CsA withdrawal may mitigate the effect of SRL on hematopoiesis. (ClinicalTrials.gov number: NCT00428064).
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| 30. |
- Johansson, Åsa, 1981-, et al.
(författare)
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Angiostatic factors normally restrict islet endothelial cell proliferation and migration : implications for islet transplantation
- 2009
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 22:12, s. 1182-1188
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Tidskriftsartikel (refereegranskat)abstract
- New blood vessel formation in transplanted islets occurs within 7-14 days posttransplantation through both the expansion of donor islet endothelium and ingrowth of blood vessels from the implantation organ. However, several studies indicate that although the islets attract recipient blood vessels, the formed intra-islet vascular network is insufficient, which affects islet posttransplant function. This study aimed to develop an in vitro model to investigate the migration and proliferation properties of isolated liver and islet endothelium. Rat islet or liver endothelium was purified using Bandeiraea simplicifolia (BS-1)-coated Dynabeads. The liver endothelium displayed an increased migration towards islet-conditioned medium, and this chemo-attractant effect was fully prevented by adding a neutralizing vascular endothelial growth factor (VEGF)-antibody. In contrast, islet-produced VEGF failed to induce islet endothelial cell migration and only had marginal effects on islet endothelial cell proliferation. These properties could, however, be activated through blocking the effects of either endostatin, thrombospondin-1 or α1-antitrypsin. In conclusion, VEGF may attract recipient blood vessels towards intrahepatically transplanted islets, but intra-islet vascular expansion is hampered by angiostatic factors present within the islets and the islet endothelium. Inhibition of these early after transplantation may provide a strategy to restore the islet vascular network and improve islet graft function.
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| 31. |
- Nadalin, Silvio, et al.
(författare)
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Role and significance of plasma citrulline in the early phase after small bowel transplantation in pigs
- 2007
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 20:5, s. 425-431
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Tidskriftsartikel (refereegranskat)abstract
- A reliable serological marker of acute cellular rejection (ACR) after small bowel transplantation (SBTx) is still missing. Plasma citrulline level (PCL) reflects the functional integrity of intestinal mucosa which is partially lost during ACR. The aim of our study was to investigate the role of PCL as marker of ACR after SBTx. Eighteen German landrace pigs were used and divided into three groups. Group 1 (G1), autologous SBTx (n = 4) as control; group 2 (G2), allogeneic SBTx without immunosuppression (IS) (n = 7) and group 3 (G3), allogeneic SBTx with IS (n = 7). IS consisted of tacrolimus and steroids without induction treatment. Observation period was 14 days. Mucosal biopsies were obtained intraoperatively and daily using a Thiry-Vella loop. ACR was differentiated into indeterminate, mild, moderate and severe using a standardized grading schema. PCL was measured daily. An ACR onset occurred generally from postoperative day 4 both in G2 and G3 as mild form and developed differently in the two groups: moderate to severe in G2 and indeterminate to mild in G3. A significant decline of PCL occurred only in cases of moderate and severe ACR, but not in cases of indeterminate and mild ACR. The PCL failed as a marker in the early diagnosis of ACR and became reliable only when advanced mucosal damage was present.
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| 32. |
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| 33. |
- Söderdahl, G., et al.
(författare)
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A prospective, randomized, multi-centre trial of systemic adjuvant chemotherapy versus no additional treatment in liver transplantation for hepatocellular carcinoma
- 2006
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Ingår i: Transplant international. - : Frontiers Media SA. - 0934-0874. ; 19:4, s. 288-94
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Tidskriftsartikel (refereegranskat)abstract
- The role of adjuvant systemic chemotherapy in liver transplantation (LT) for hepatocellular carcinoma (HCC) is controversial. Here, we report the results of a Nordic prospective, randomized, multi-centre trial of systemic low-dose doxorubicin in patients with HCC. Between February 1996 and April 2004, 46 patients were randomized to receive either neoadjuvant doxorubicin in combination with LT (chemo group; n = 19) or LT alone (control group; n = 27). In the chemo group, doxorubicin was administered intravenously, 10 mg/m(2) weekly, starting from acceptance onto the waiting list for LT. One intraoperative dose of 15 mg/m(2) was given, and postoperatively doxorubicin was given weekly at a dose of 10 mg/m(2), depending on the clinical course, up to a cumulative dose of 400 mg/m(2). Actuarial, 3-year overall survival (OS) and disease-free survival (DFS) in the control group were 70% and 50%, respectively. In the chemo group, both OS and DFS were 63%. Freedom from recurrence at 3 years was 55% in the control group and 74% in the chemo group. None of the differences was statistically significant. Neoadjuvant treatment with systemic low-dose doxorubicin seems not to improve either survival or freedom from recurrence in patients with HCC undergoing LT.
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| 34. |
- Yamamoto, Shinji, et al.
(författare)
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Long-term consequences of domino liver transplantation using familial amyloidotic polyneuropathy grafts
- 2007
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 13:6, s. S223-S223
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Tidskriftsartikel (refereegranskat)abstract
- Domino liver transplantation (DLT) using grafts from patients with familial amyloidotic polyneuropathy (FAP) is an established procedure at many transplantation centers. However, data evaluating the long-term outcome of DLT are limited. The aim of the present study was to analyze the risk of de novo polyneuropathy, possibly because of amyloidosis, and the patient survival after DLT. At our department, 28 DLT using FAP grafts were conducted between January 1997 and December 2005. One patient was twice subjected to DLT. Postoperative neurological monitoring of peripheral nerve function was performed with electroneurography (ENeG) in 20 cases. An ENeG index based on 12 parameters was calculated and correlated to age and/or height. Three patients developed ENeG signs of polyneuropathy 2-5 years after the DLT, but with no clinical symptoms. The 1-, 3- and 5-year actuarial patient survival in hepatocellular carcinoma (HCC) patients (n = 12) and non-HCC patients (n = 15) was 67%, 15%, 15% and 93%, 93%, 80%, respectively (P = 0.001). Development of impaired nerve conduction in a proportion of patients may indicate that de novo amyloidosis occurs earlier than previously expected. Survival after DLT was excellent except in patients with advanced HCC.
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| 35. |
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| 36. |
- Barkholt, L M, et al.
(författare)
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Stool cultures obtained before liver transplantation are useful for choice of perioperative antibiotic prophylaxis
- 1997
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 10:6, s. 432-438
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial infections, especially cholangitis, are still common complications after liver transplantation (LTx). During recent years, multiresistant enterococci have become a nosocomial problem in transplant units. The present prospective study on 26 patients, including 24 patients with chronic liver disease, demonstrated that enterococci were the predominant micro-organism involved in post-LTx bacterial infections. They were cultured in the feces and in other sites of 10 out of 13 (77%) patients who underwent extensive examinations. Ampicillin-resistant Enterococcus faecium strains were isolated in urine or feces of 2 of the 13 patients prior to LTx. Similarly, resistance to ampicillin and gentamicin, the empirically used antibiotics for patients with fever of unknown origin, was found in E. faecium strains in 3 and 2 patients, respectively. Moreover, multiresistant E. faecium and E. faecalis strains were demonstrated in 46% of the patients in the postoperative period (3 months). However, no vancomycin-resistant enterococci were isolated. The use of antibiotics within 4 months prior to LTx significantly increased the risk of developing ampicillin-resistant bacteria at the time of LTx and of infections with bacteria of enteric origin after LTx (P = 0.03 and 0.01, respectively). We conclude that stool and urine cultures performed prior to LTX may be useful for selecting prophylactic antibiotic regimens.
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| 37. |
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| 38. |
- Lennerling, Annette, 1963, et al.
(författare)
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Written information for potential living kidney donors.
- 2004
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 17:8, s. 449-52
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Tidskriftsartikel (refereegranskat)abstract
- To meet the constantly growing demand for organs for transplantation the use of living related and unrelated donors continues to increase. Transplant units with a living-donor programme often provide written information to their potential kidney donors. We saw a need to assess the contents of these brochures. Written information for potential live kidney donors was requested from different Transplant units throughout the world. We obtained and analysed 16 different brochures from 14 countries. The general approach ranged from persuasive to almost deterring. Sixteen main themes were identified in the information material. Eight of those were considered paramount, namely voluntarism, medical suitability, short-term donor risks, long-term donor risks, risk of graft loss, outcome with and without a living donor, postoperative course, and financial conditions. Five brochures covered all these crucial matters. When mentioned, examples and interpretations of donor risks were very dissimilar. Furthermore, the conditions for donation were obviously very different in the various countries. This review points at essential issues to be included in the written information for living kidney donors. All transplant units with a living-donor programme should provide such information, thus enabling the potential donor to make a thorough decision. PMID: 15322746 [PubMed - indexed for MEDLINE]
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| 39. |
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| 40. |
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| 41. |
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| 42. |
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| 43. |
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| 44. |
- Ansari, David, et al.
(författare)
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Human Leukocyte Antigen Matching in Heart Transplantation: Systematic Review and Meta-analysis.
- 2014
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Ingår i: Transplant International. - : Frontiers Media SA. - 1432-2277 .- 0934-0874. ; 27:8, s. 793-804
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Tidskriftsartikel (refereegranskat)abstract
- Allocation of donors with regard to human leukocyte antigen (HLA) is controversial in heart transplantation. This paper is a systematic review and meta-analysis of the available evidence. PubMed, Embase, and the Cochrane Library were searched systematically for studies that addressed the effects of HLA matching on outcome after heart transplantation. Fifty-seven studies met the eligibility criteria. 34 studies had graft rejection as outcome, with 26 of the studies reporting a significant reduction in graft rejection with increasing degree of HLA matching. Thirteen of 18 articles that reported on graft failure found that it decreased significantly with increasing HLA match. Two multicenter studies and 9 single-center studies provided sufficient data to provide summary estimates at 12 months. Pooled comparisons showed that graft survival increased with fewer HLA-DR mismatches [0-1 vs. 2 mismatches: risk ratio (RR)=1.09 (95% confidence interval (CI): 1.01-1.19; P=0.04)]. Having fewer HLA-DR mismatches (0-1 vs. 2) reduced the incidence of acute rejection [(RR=0.81 (0.66-0.99; P=0.04)]. Despite the considerable heterogeneity between studies, the short observation time, and older data, HLA matching improves graft survival in heart transplantation. Prospective HLA-DR matching is clinically feasible and should be considered as a major selection criterion. This article is protected by copyright. All rights reserved.
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| 45. |
- Ballesté, Chloe, et al.
(författare)
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Design and implementation of the European-Mediterranean Postgraduate Programme on Organ Donation and Transplantation (EMPODaT) for Middle East/North Africa countries
- 2021
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 34:8, s. 1553-1565
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Tidskriftsartikel (refereegranskat)abstract
- This prospective study reports the design and results obtained after the EMPODaT project implementation. This project was funded by the Tempus programme of the European Commission with the objective to implement a common postgraduate programme on organ donation and transplantation (ODT) in six selected universities from Middle East/North Africa (MENA) countries (Egypt, Lebanon and Morocco). The consortium, coordinated by the University of Barcelona, included universities from Spain, Germany, Sweden and France. The first phase of the project was to perform an analysis of the current situation in the beneficiary countries, including existing training programmes on ODT, Internet connection, digital facilities and competences, training needs, and ODT activity and accreditation requirements. A total of 90 healthcare postgraduate students participated in the 1-year training programme (30 ECTS academic credits). The methodology was based on e-learning modules and face-to-face courses in English and French. Training activities were evaluated through pre- and post-tests, self-assessment activities and evaluation charts. Quality was assessed through questionnaires and semi-structured interviews. The project results on a reproducible and innovative international postgraduate programme, improvement of knowledge, satisfaction of the participants and confirms the need on professionalizing the activity as the cornerstone to ensure organ transplantation self-sufficiency in MENA countries. © 2021 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.
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| 46. |
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| 47. |
- Benoni, Henrik, et al.
(författare)
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Relative and absolute cancer risks among Nordic kidney transplant recipients-a population-based study
- 2020
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Ingår i: Transplant International. - : WILEY. - 0934-0874 .- 1432-2277. ; 33:12, s. 1700-1710
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Tidskriftsartikel (refereegranskat)abstract
- Kidney transplant recipients (KTRs) have an increased cancer risk compared to the general population, but absolute risks that better reflect the clinical impact of cancer are seldom estimated. All KTRs in Sweden, Norway, Denmark, and Finland, with a first transplantation between 1995 and 2011, were identified through national registries. Post-transplantation cancer occurrence was assessed through linkage with cancer registries. We estimated standardized incidence ratios (SIR), absolute excess risks (AER), and cumulative incidence of cancer in the presence of competing risks. Overall, 12 984 KTRs developed 2215 cancers. The incidence rate of cancer overall was threefold increased (SIR 3.3, 95% confidence interval [CI]: 3.2-3.4). The AER of any cancer was 1560 cases (95% CI: 1468-1656) per 100 000 person-years. The highest AERs were observed for nonmelanoma skin cancer (838, 95% CI: 778-901), non-Hodgkin lymphoma (145, 95% CI: 119-174), lung cancer (126, 95% CI: 98.2-149), and kidney cancer (122, 95% CI: 98.0-149). The five- and ten-year cumulative incidence of any cancer was 8.1% (95% CI: 7.6-8.6%) and 16.8% (95% CI: 16.0-17.6%), respectively. Excess cancer risks were observed among Nordic KTRs for a wide range of cancers. Overall, 1 in 6 patients developed cancer within ten years, supporting extensive post-transplantation cancer vigilance.
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| 48. |
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| 49. |
- Berglund, Erik, et al.
(författare)
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Safety and pharmacodynamics of anti-CD2 monoclonal antibody treatment in cynomolgus macaques - an experimental study
- 2020
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Ingår i: Transplant International. - HOBOKEN NJ USA : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 33:1, s. 98-107
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Tidskriftsartikel (refereegranskat)abstract
- Anti-CD2 treatment provides targeted immunomodulatory properties that have demonstrated clinical usefulness to condition the immune system and to treat transplant rejection. The treatment is species-specific due to structural CD2 antigen differences between nonhuman primates and humans. Herein, we report the safety profile and efficacy of two modifications of the same anti-CD2 monoclonal antibody in cynomolgus macaques. Twelve subjects received one i.v. anti-CD2 (of rat or rhesus type) dose each, range 1-4 mg/kg, and were followed for 1-7 days. Treatment effects were evaluated with flow cytometry on peripheral blood and histopathological evaluation of secondary lymphoid organs. In vitro inhibitory activity on primary MHC disparate mixed lymphocyte reactions (MLRs) was determined. Upon anti-CD2 treatment, CD4(+), CD8(+) memory subsets were substantially depleted. Naive T cells and Tregs were relatively spared and exhibited lower CD2 expression than memory T cells. Early immune reconstitution was noted for naive cells, while memory counts had not recovered after one week. Both antibodies displayed a concentration-dependent MLR inhibition. Lymph node examination revealed no significant lymphocyte depletion. None of the animals experienced any significant study drug-related adverse events. This study outlines the safety and pharmacodynamic profile of primate-specific anti-CD2 treatment, relevant for translation of anti-CD2-based animal models into clinical trials.
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| 50. |
- Bergström, Marcus, et al.
(författare)
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Autologous regulatory T cells in clinical intraportal allogenic pancreatic islet transplantation
- 2021
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Ingår i: Transplant International. - : John Wiley & Sons. - 0934-0874 .- 1432-2277. ; 34:12, s. 2816-2823
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic islet transplantation in type 1 diabetes requires lifelong immunosuppression to prevent graft rejection. This medication can cause adverse effects and increases the susceptibility for infections and malignancies. Adoptive therapies with regulatory T cells (Tregs) have shown promise in reducing the need for immunosuppression in human transplantation settings but have previously not been evaluated in islet transplantation. In this study, five patients with type 1 diabetes undergoing intraportal allogeneic islet transplantation were co-infused with polyclonal autologous Tregs under a standard immunosuppressive regimen. Patients underwent leaukapheresis from which Tregs were purified by magnetic-activated cell sorting (MACS) and cryopreserved until transplantation. Dose ranges of 0.14–1.27 × 106 T cells per kilo bodyweight were transplanted. No negative effects were seen related to the Treg infusion, regardless of cell dose. Only minor complications related to the immunosuppressive drugs were reported. This first-in-man study of autologous Treg infusion in allogenic pancreatic islet transplantation shows that the treatment is safe and feasible. Based on these results, future efficacy studies will be developed under the label of advanced therapeutic medical products (ATMP), using modified or expanded Tregs with the aim of minimizing the need for chronic immunosuppressive medication in islet transplantation.
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