| 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. |
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| 4. |
- 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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| 5. |
- 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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| 6. |
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| 7. |
- 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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| 8. |
- 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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| 9. |
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| 10. |
- 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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