Transplantation research最新文献

{"title":"Alemtuzumab induction therapy in solid organ transplantation.","authors":"Peter J Friend","doi":"10.1186/2047-1440-2-S1-S5","DOIUrl":"https://doi.org/10.1186/2047-1440-2-S1-S5","url":null,"abstract":"<p><p>Alemtuzumab (Campath) is a monoclonal antibody that has a profound lymphocyte-depleting effect, targeting the CD52 antigen that is present on all lymphocytes. Alemtuzumab has been used for the treatment of chronic lymphocytic leukaemia and various autoimmune disorders, and has also shown potential as an induction agent in the prevention of rejection following solid organ transplantation. Alemtuzumab has been studied in randomised controlled trials and has demonstrated low levels of rejection in renal transplant recipients compared with other induction agents, albeit mainly in the early months following transplantation. Studies have shown that alemtuzumab enables the use of lower calcineurin inhibitor (CNI) maintenance drugs; however, this reduction in nephrotoxic immunosuppression has not consistently been matched by an improvement in renal function. The hypothesis has been suggested that alemtuzumab might allow the development of immunosuppressive regimens that avoid CNIs completely; studies have investigated the combination of alemtuzumab with mammalian target of rapamycin-inhibitor maintenance therapy, and, in particular, sirolimus. Initial studies with this combination showed that regimens of sirolimus alone and of sirolimus with mycophenolate mofetil were unsuccessful, with a high rate of rejection and complications. Subsequent studies have targeted the combination of alemtuzumab induction with a short course of a CNI, before switching to maintenance therapy with sirolimus. This regimen might combine good protection from acute cellular rejection and chronic nephrotoxicity. A randomised controlled trial has been established to study this regimen, with results pending. </p>","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":"2 Suppl 1","pages":"S5"},"PeriodicalIF":0.0,"publicationDate":"2013-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2047-1440-2-S1-S5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32149771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new risk score model to predict the presence of significant coronary artery disease in renal transplant candidates.","authors":"Luís Henrique Wolff Gowdak,&nbsp;Flávio Jota de Paula,&nbsp;Luiz Antônio Machado César,&nbsp;Luiz Aparecido Bortolotto,&nbsp;José Jayme Galvão de Lima","doi":"10.1186/2047-1440-2-18","DOIUrl":"10.1186/2047-1440-2-18","url":null,"abstract":"<p><strong>Background: </strong>Renal transplant candidates are at high risk of coronary artery disease (CAD). We sought to develop a new risk score model to determine the pre-test probability of the occurrence of significant CAD in renal transplant candidates.</p><p><strong>Methods: </strong>A total of 1,060 renal transplant candidates underwent a comprehensive cardiovascular risk evaluation. Patients considered at high risk of CAD (age ≥50 years, with either diabetes mellitus (DM) or cardiovascular disease (CVD)), or having noninvasive testing suggestive of CAD were referred for coronary angiography (n = 524). Significant CAD was defined by the presence of luminal stenosis ≥70%. A binary logistic regression model was built, and the resulting logistic regression coefficient B for each variable was multiplied by 10 and rounded to the next whole number. For each patient, a corresponding risk score was calculated and the receiver operating characteristic (ROC) curve was constructed.</p><p><strong>Results: </strong>The final equation for the model was risk score = (age × 0.4) + (DM × 9) + (CVD × 14) and for the probability of CAD (%) = (risk score × 2) - 23. The corresponding ROC for the accuracy of the diagnosis of CAD was 0.75 (P <0.0001) in the developmental model.</p><p><strong>Conclusions: </strong>We developed a simple clinical risk score to determine the pre-test probability of significant CAD in renal transplant candidates. This model may help those directly involved in the care of patients with end-stage renal disease being considered for transplantation in an attempt to reduce the rate of cardiovascular events that presently hampers the long-term prognosis of such patients.</p>","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":" ","pages":"18"},"PeriodicalIF":0.0,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2047-1440-2-18","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40281477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standardization of whole blood immune phenotype monitoring for clinical trials: panels and methods from the ONE study.","authors":"Mathias Streitz,&nbsp;Tewfik Miloud,&nbsp;Michael Kapinsky,&nbsp;Michael R Reed,&nbsp;Robert Magari,&nbsp;Edward K Geissler,&nbsp;James A Hutchinson,&nbsp;Katrin Vogt,&nbsp;Stephan Schlickeiser,&nbsp;Anders Handrup Kverneland,&nbsp;Christian Meisel,&nbsp;Hans-Dieter Volk,&nbsp;Birgit Sawitzki","doi":"10.1186/2047-1440-2-17","DOIUrl":"https://doi.org/10.1186/2047-1440-2-17","url":null,"abstract":"<p><strong>Background: </strong>Immune monitoring by flow cytometry is a fast and highly informative way of studying the effects of novel therapeutics aimed at reducing transplant rejection or treating autoimmune diseases. The ONE Study consortium has recently initiated a series of clinical trials aimed at using different cell therapies to promote tolerance to renal allografts. To compare the effectiveness of different cell therapies, the consortium developed a robust immune monitoring strategy, including procedures for whole blood (WB) leukocyte subset profiling by flow cytometry.</p><p><strong>Methods: </strong>Six leukocyte profiling panels computing 7- to 9-surface marker antigens for monitoring the major leukocyte subsets as well as characteristics of T cell, B cell, and dendritic cell (DC) subsets were designed. The precision and variability of these panels were estimated. The assay was standardized within eight international laboratories using Flow-Set Pro beads for mean fluorescence intensity target definition and the flow cytometer setup procedure. Standardization was demonstrated by performing inter-site comparisons.</p><p><strong>Results: </strong>Optimized methods for sample collection, storage, preparation, and analysis were established, including protocols for gating target subsets. WB specimen age testing demonstrated that staining must be performed within 4 hours of sample collection to keep variability low, meaning less than or equal to 10% for the majority of defined leukocyte subsets. Inter-site comparisons between all participating centers testing shipped normal WB revealed good precision, with a variability of 0.05% to 30% between sites. Intra-assay analyses revealed a variability of 0.05% to 20% for the majority of subpopulations. This was dependent on the frequency of the particular subset, with smaller subsets showing higher variability. The intra-assay variability performance defined limits of quantitation (LoQ) for subsets, which will be the basis for assessing statistically significant differences achieved by the different cell therapies.</p><p><strong>Conclusions: </strong>Local performance and central analysis of the ONE Study flow cytometry panel yields acceptable variability in a standardized assay at multiple international sites. These panels and procedures with WB allow unmanipulated analysis of changes in absolute cell numbers of leukocyte subsets in single- or multicenter clinical trials. Accordingly, we propose the ONE Study panel may be adopted as a standardized method for monitoring patients in clinical trials enrolling transplant patients, particularly trials of novel tolerance promoting therapies, to facilitate fair and meaningful comparisons between trials.</p>","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":" ","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2013-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2047-1440-2-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40266651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-13 signaling via IL-13Rα2 triggers TGF-β1-dependent allograft fibrosis.","authors":"Stefan M Brunner,&nbsp;Gabriela Schiechl,&nbsp;Rebecca Kesselring,&nbsp;Maria Martin,&nbsp;Saidou Balam,&nbsp;Hans J Schlitt,&nbsp;Edward K Geissler,&nbsp;Stefan Fichtner-Feigl","doi":"10.1186/2047-1440-2-16","DOIUrl":"https://doi.org/10.1186/2047-1440-2-16","url":null,"abstract":"<p><strong>Background: </strong>Allograft fibrosis still remains a critical problem in transplantation, including heart transplantation. The IL-13/TGF-β1 interaction has previously been identified as a key pathway orchestrating fibrosis in different inflammatory immune disorders. Here we investigate if this pathway is also responsible for allograft fibrosis and if interference with the IL-13/TGF-β1 interaction prevents allograft fibrosis.</p><p><strong>Methods: </strong>FVB or control DBA/1 donor hearts were transplanted heterotopically into DBA/1 recipient mice and hearts were explanted at day 60 and 100 post-transplantation. Cardiac tissue was examined by Masson's trichrome staining and immunohistochemistry for CD4, CD8, CD11b, IL-13, Fas ligand, matrix metalloproteinase (MMP)-1, MMP-13, β2-microglobulin, and Gremlin-1. Graft-infiltrating cells were isolated and analyzed by flow cytometry. IL-13 and TGF-β1 levels were determined by enzyme-linked immunosorbent assay (ELISA) and the amount of collagen was quantified using a Sircol assay; IL-13Rα2 expression was detected by Western blotting. In some experiments IL-13/ TGF-β1 signaling was blocked with specific IL-13Rα2 siRNA. Additionally, a PCR array of RNA isolated from the allografts was performed to analyze expression of multiple genes involved in fibrosis.</p><p><strong>Results: </strong>Both groups survived long-term (>100 days). The allogeneic grafts were infiltrated by significantly increased numbers of CD4+ (P <0.0001), CD8+ (P <0.0001), and CD11b+ cells (P = 0.0065) by day 100. Furthermore, elevated IL-13 levels (P = 0.0003) and numbers of infiltrating IL-13+ cells (P = 0.0037), together with an expression of IL-13Rα2, were detected only within allografts. The expression of IL-13 and IL-13Rα2 resulted in significantly increased TGF-β1 levels (P <0.0001), higher numbers of CD11bhighGr1intermediateTGF-β1+ cells, and elevated cardiac collagen deposition (P = 0.0094). The allograft fibrosis found in these experiments was accompanied by upregulation of multiple profibrotic genes, which was confirmed by immunohistochemical stainings of allograft tissue. Blockage of the IL-13/TGF-β1 interaction by IL-13Rα2 siRNA led to lower numbers of CD11bhighGr1intermediateTGF-β1+, CD4+, CD8+, and CD11b+ cells, and prevented collagen deposition (P = 0.0018) within these allografts.</p><p><strong>Conclusions: </strong>IL-13 signaling via IL-13Rα2 induces TGF-β1 and causes allograft fibrosis in a murine model of chronic transplant rejection. Blockage of this IL-13/TGF-β1 interaction by IL-13Rα2 siRNA prevents cardiac allograft fibrosis. Thus, IL-13Rα2 may be exploitable as a future target to reduce allograft fibrosis in organ transplantation.</p>","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":" ","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2013-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2047-1440-2-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40253440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term follow-up of kidney transplant recipients: comparison of hospitalization rates to the general population.","authors":"Ying Jiang,&nbsp;Paul J Villeneuve,&nbsp;Douglas Schaubel,&nbsp;Yang Mao,&nbsp;Panduranga Rao,&nbsp;Howard Morrison","doi":"10.1186/2047-1440-2-15","DOIUrl":"https://doi.org/10.1186/2047-1440-2-15","url":null,"abstract":"<p><strong>Background: </strong>Kidney transplant recipients are recognized as a vulnerable population that is at increased risk of adverse health outcomes. However, there have been few studies that have compared hospital-related morbidity of these patients to the general population, and how this differs with respect to time since transplantation. Such analyses are useful in estimating the health burden in this patient population.</p><p><strong>Methods: </strong>We assembled a population-based Canadian cohort (excluding Quebec) of 6,116 kidney transplant recipients who underwent transplantation between 1 April 2001 and 31 December 2008. Record linkage was used to identify hospital discharge records of these patients from 1 April 2001 through 31 March 2009. Hospital discharges were tabulated across the main disease chapters of the ICD10, and person-years of follow-up were calculated across age and sex strata. Comparisons of hospital-related morbidity to the general population were made by using a standardized hospitalization ratio (SHR). For those who underwent transplantation in 2004, stratified analyses were performed to explore differences in hospital discharge rates both before and after transplantation.</p><p><strong>Results: </strong>After excluding hospitalizations due to complications from transplantation, when compared to the general population, transplant recipients were approximately 6.4 (95% CI: 6.3, 6.5) times more likely to be hospitalized during follow-up. The SHRs were highest during the time periods proximate to transplantation, and then decreased to approximately a five-fold increase from 3 years post transplantation onwards. The largest disease-specific excesses were observed with infectious diseases and diseases of the endocrine system. Among those who underwent transplantation in 2004, the SHR decreased from 11.2 to 5.0 in the periods before and after surgery, respectively.</p><p><strong>Conclusions: </strong>Our results indicate that, even more than 5-years post transplantation, there remains a more than six-fold difference in hospitalization rates relative to the general population. Additional work is needed to confirm these findings, and to develop strategies to reduce long-term morbidity in this patient population.</p>","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":"2 1","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2013-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2047-1440-2-15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31679218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of concentration-controlled everolimus with reduced-dose cyclosporine in Japanese de novo renal transplant patients: 12-month results.","authors":"Kota Takahashi,&nbsp;Kazuharu Uchida,&nbsp;Norio Yoshimura,&nbsp;Shiro Takahara,&nbsp;Satoshi Teraoka,&nbsp;Rie Teshima,&nbsp;Catherine Cornu-Artis,&nbsp;Eiji Kobayashi","doi":"10.1186/2047-1440-2-14","DOIUrl":"https://doi.org/10.1186/2047-1440-2-14","url":null,"abstract":"<p><strong>Background: </strong>No study to date has evaluated the efficacy and safety of everolimus with reduced-exposure cyclosporine in Japanese de-novo renal transplant (RTx) patients.</p><p><strong>Methods: </strong>This 12-month, multicenter, open-label study randomized (1:1) 122 Japanese de-novo RTx patients to either an everolimus regimen (1.5 mg/day starting dose (target trough: 3 to 8 ng/ml) + reduced-dose cyclosporine) or a mycophenolate mofetil (MMF) regimen (2 g/day + standard dose cyclosporine). All patients received basiliximab and corticosteroids. Key endpoints at month 12 were composite efficacy failure (treated biopsy-proven acute rejection, graft loss, death, or loss to follow-up) and renal function (estimated glomerular filtration rate; Modification of Diet in Renal Disease-4).</p><p><strong>Results: </strong>Clear cyclosporine exposure reduction was achieved in the everolimus group throughout the study (52% reduction at month 12). Month 12 efficacy failure rates showed everolimus 1.5 mg to be non-inferior to MMF (11.5% vs. 11.5%). The median estimated glomerular filtration rate at month 12 was 58.00 ml/minute/1.73 m2 in the everolimus group versus 55.25 ml/minute/1.73 m2 in the MMF group (P = 0.063). Overall, the incidence of adverse events was comparable between the groups with some differences in line with the known safety profile of the treatments. The everolimus group had a higher incidence of wound healing events and edema, whereas a higher rate of cytomegalovirus infections was reported in the MMF group.</p><p><strong>Conclusions: </strong>This study confirmed the efficacy of everolimus 1.5 mg/day (target trough: 3 to 8 ng/ml) in Japanese RTx patients for preventing acute rejection, while allowing for substantial cyclosporine sparing. Renal function and safety findings were comparable with previous reports from other RTx populations.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov number: NCT00658320.</p>","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":"2 1","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2013-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2047-1440-2-14","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31591138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of in situ versus ex situ perfusion on flow and microcirculation in kidney procurement: research on a porcine model.","authors":"Daniel Foltys,&nbsp;Moritz Kaths,&nbsp;Mari Strempel,&nbsp;Uwe Scheuermann,&nbsp;Axel Heimann,&nbsp;Veronika Weyer,&nbsp;Torsten Hansen,&nbsp;Oliver Kempski,&nbsp;Gerd Otto","doi":"10.1186/2047-1440-2-13","DOIUrl":"https://doi.org/10.1186/2047-1440-2-13","url":null,"abstract":"","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":"2 1","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2013-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2047-1440-2-13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31566471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extended pancreas donor program - the EXPAND study rationale and study protocol.","authors":"Andrea Proneth,&nbsp;Andreas A Schnitzbauer,&nbsp;Florian Zeman,&nbsp;Johanna R Foerster,&nbsp;Ines Holub,&nbsp;Helmut Arbogast,&nbsp;Wolf O Bechstein,&nbsp;Thomas Becker,&nbsp;Carsten Dietz,&nbsp;Markus Guba,&nbsp;Michael Heise,&nbsp;Sven Jonas,&nbsp;Stephan Kersting,&nbsp;Jürgen Klempnauer,&nbsp;Steffen Manekeller,&nbsp;Volker Müller,&nbsp;Silvio Nadalin,&nbsp;Björn Nashan,&nbsp;Andreas Pascher,&nbsp;Falk Rauchfuss,&nbsp;Michael A Ströhlein,&nbsp;Peter Schemmer,&nbsp;Peter Schenker,&nbsp;Stefan Thorban,&nbsp;Thomas Vogel,&nbsp;Axel O Rahmel,&nbsp;Richard Viebahn,&nbsp;Bernhard Banas,&nbsp;Edward K Geissler,&nbsp;Hans J Schlitt,&nbsp;Stefan A Farkas","doi":"10.1186/2047-1440-2-12","DOIUrl":"https://doi.org/10.1186/2047-1440-2-12","url":null,"abstract":"<p><strong>Background: </strong>Simultaneous pancreas kidney transplantation (SPK), pancreas transplantation alone (PTA) or pancreas transplantation after kidney (PAK) are the only curative treatment options for patients with type 1 (juvenile) diabetes mellitus with or without impaired renal function. Unfortunately, transplant waiting lists for this indication are increasing because the current organ acceptability criteria are restrictive; morbidity and mortality significantly increase with time on the waitlist. Currently, only pancreas organs from donors younger than 50 years of age and with a body mass index (BMI) less than 30 are allocated for transplantation in the Eurotransplant (ET) area. To address this issue we designed a study to increase the available donor pool for these patients.</p><p><strong>Methods/design: </strong>This study is a prospective, multicenter (20 German centers), single blinded, non-randomized, two armed trial comparing outcome after SPK, PTA or PAK between organs with the currently allowed donor criteria versus selected organs from donors with extended criteria. Extended donor criteria are defined as organs procured from donors with a BMI of 30 to 34 or a donor age between 50 and 60 years. Immunosuppression is generally standardized using induction therapy with Myfortic, tacrolimus and low dose steroids. In principle, all patients on the waitlist for primary SPK, PTA or PAK are eligible for the clinical trial when they consent to possibly receiving an extended donor criteria organ. Patients receiving an organ meeting the current standard criteria for pancreas allocation (control arm) are compared to those receiving extended criteria organ (study arm); patients are blinded for a follow-up period of one year. The combined primary endpoint is survival of the pancreas allograft and pancreas allograft function after three months, as an early relevant outcome parameter for pancreas transplantation.</p><p><strong>Discussion: </strong>The EXPAND Study has been initiated to investigate the hypothesis that locally allocated extended criteria organs can be transplanted with similar results compared to the currently allowed standard ET organ allocation. If our study shows a favorable comparison to standard organ allocation criteria, the morbidity and mortality for patients waiting for transplantation could be reduced in the future.</p><p><strong>Trial registration: </strong>Trial registered at: NCT01384006.</p>","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":"2 1","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2047-1440-2-12","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31548011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction with interleukin-2 antagonist for transplantation of kidneys from older deceased donors: an observational study.","authors":"Kristian Heldal,&nbsp;Solveig Thorarinsdottir,&nbsp;Anders Hartmann,&nbsp;Torbjørn Leivestad,&nbsp;Anna V Reisæter,&nbsp;Aksel Espen Foss,&nbsp;Karsten Midtvedt","doi":"10.1186/2047-1440-2-11","DOIUrl":"https://doi.org/10.1186/2047-1440-2-11","url":null,"abstract":"<p><strong>Background: </strong>The most important limiting factor in kidney transplantation is the scarcity of donor organs. Consequently, there is an increased use worldwide of kidneys from older deceased donors. High donor age is a known risk factor for acute cellular rejection and premature graft failure, and the optimal immunosuppressive regimen in these circumstances remains to be established.</p><p><strong>Methods: </strong>We investigated whether induction treatment with an interleukin 2 (IL-2) receptor antagonist improves graft survival and reduces rejection episodes in recipients of kidneys from deceased donors aged ≥ 60 years. Data were retrieved for all recipients transplanted at our center from 2004 to 2009 with a kidney from a deceased donor aged > 60 years. The outcome was compared between recipients treated with (IL-2 plus) or without (IL-2 minus) an IL-2 receptor antagonist. All recipients received a calcineurin inhibitor, steroids and mycophenolate.</p><p><strong>Results: </strong>A total of 232 first-transplant recipients were included (IL-2 plus = 149, IL-2 minus = 83). IL-2 minus was associated with increased risk of early acute rejection (OR 2.42; 95% CI 1.25 to 4.68, P = 0.009) and steroid-resistant rejection (OR 8.04; 2.77 to 23.25, P< 0.001). IL-2 plus patients had superior two-year estimated uncensored (87% versus 70%, P = 0.001) and death-censored (95% versus 79%, P< 0.001) graft survival.</p><p><strong>Conclusions: </strong>Induction treatment with IL-2 receptor antagonist was associated with a reduction in acute rejection episodes and improved two-year graft survival in patients transplanted with kidneys from older deceased donors.</p>","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":"2 1","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2013-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2047-1440-2-11","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31625318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploiting paracrine mechanisms of tissue regeneration to repair damaged organs.","authors":"Diana F Anthony,&nbsp;Paul G Shiels","doi":"10.1186/2047-1440-2-10","DOIUrl":"https://doi.org/10.1186/2047-1440-2-10","url":null,"abstract":"<p><p>Stem cells have been studied for many years for their potential to repair damaged organs in the human body. Although many different mechanisms have been suggested as to how stem cells may initiate and facilitate repair processes, much remains unknown. Recently, there has been considerable interest in the idea that stem cells may exert their effects in vivo via paracrine actions. This could involve the release of cytokines, growth factors or secreted extracellular vesicles. This article reviews the role that paracrine actions may play in tissue regeneration. In particular, it considers how microvesicles, as a mediator or modulator of paracrine action, can be exploited as a tool for non-cell-based therapies in regenerative medicine. </p>","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":"2 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2013-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2047-1440-2-10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31522134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}