Vous êtes ici : Accueil > Espace Médecin > La revue de Presse > Transplantation

Mise jour le : 30-03-2017




Les derniers abstracts de la revue Transplantation - Current Issue :


    Date de mise en ligne : Jeudi 01 janvier 1970
    Wright, Alissa J.; Rose, Caren; Toews, Maeghan; Paquet, Michel; Corsilli, Daniel; Le Cailhier, Jean-François; Gill, John S.
    An Exception to the Rule or a Rule for the Exception? The Potential of Using HIV-Positive Donors in Canada
    Abstract: Selected human immunodeficiency virus (HIV)-infected patients with end organ failure can safely receive an organ transplant from an HIV uninfected donor. Recent demonstration of the short term safety of organ transplantation between HIV-infected persons prompted a change in US American law to allow such transplantations. Prompted by the recent completion of the first organ transplantation between HIV-infected persons in Canada, we review Canadian law regarding the use of organs from HIV-infected donors, estimate the number of potential HIV-infected donors in Canada, and critically review considerations related to advancing organ transplantation from HIV-infected donors in Canada. Existing legislation allows organ transplantation from an HIV-infected donor under exceptional medical circumstances and therefore no change in legislation is required to increase utilization of organs from HIV-infected donors for transplantation in Canada. Among 335,793 hospital deaths between 2005 and 2009 in Canadian provinces excluding Quebec, 39 potential HIV-infected donors were identified. The actual number of HIV potential donors is estimated to be approximately 60% lower (3-5 potential donor per year), if the absence of viremia is required for transplantation. Although offering all Canadians the opportunity to donate organs is a laudable goal, further research to understand the need for HIV-positive donors and the willingness of HIV-positive recipients to accept organs from HIV-positive donors is needed to inform future policy regarding organ donation from HIV-infected persons in Canada.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Issa, Fadi
    Research Highlights
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Chittka, Dominik; Hutchinson, James A.
    Pregnancy After Renal Transplantation
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Weiner, Scott G.; Malek, Sayeed K.; Price, Christin N.
    The Opioid Crisis and Its Consequences
    imageNo abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Rogers, Rodney L.; Stock, Peter G.
    Canadian Laws Are on Target—But Is the Transplant Community?
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Grossi, Paolo Antonio
    Risk Assessment for HIV+ Organ Donors: Is the CD4 T Cell Count a Marker of Increased Risk of Transmissible Diseases?
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Michaels, Marian G.; Humar, Atul
    Cytomegalovirus in the Pediatric Transplant Recipient: Where Are We Now?
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Fairchild, Robert L.
    Fingering a Natural Culprit During Antibody-Mediated Rejection
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Ambadapadi, Sriram
    Inhibition of Complement: Tackling of Both Innate and Adaptive Immune Responses to Dampen Rejection
    imageNo abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Cowan, Peter J.; Ierino, Francesco L.
    Reducing the Threshold for Clinical Renal Xenotransplantation
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Tsampalieros, Anne; Knoll, Greg A.; Molnar, Amber O.; Fergusson, Nicholas; Fergusson, Dean A.
    Corticosteroid Use and Growth After Pediatric Solid Organ Transplantation: A Systematic Review and Meta-Analysis
    imageBackground: A number of corticosteroid minimization and avoidance protocols for post–solid organ transplant have been developed. The study objective was to examine the effect of corticosteroid withdrawal/avoidance on growth and safety parameters in pediatric solid organ transplant recipients. Methods: A systematic review using Medline and Embase was performed. All randomized controlled trials (RCT) and observational studies comparing corticosteroid withdrawal/avoidance to controls receiving corticosteroids in pediatric transplant recipients which reported growth as change in height or final height were included. Two reviewers independently abstracted study data and assessed quality. Results: The search yielded 930 records, 14 separate studies involving 1146 patients. Renal RCTs (n = 5) showed that corticosteroid withdrawal/avoidance was associated with a significant increase in growth (mean difference in height standard deviation score [SDS], 0.18; 95% confidence interval [95% CI], 0.07-0.29; P = 0.001) compared with those remaining on steroids. In liver RCTs (n = 2), mean difference in height SDS was −0.20 (95% CI, −1.08 to 0.68; P = 0.66). Results for renal observational studies (n = 5) was 0.34 (95% CI, 0.03-0.65; P = 0.03). The most pronounced effect was seen in prepubertal children with SDS of 0.28 (95% CI, 0.14-0.41; P < 0.0001). In pubertal participants this was not observed (SDS, 0.06; 95% CI, −0.04 to 0.15; P = 0.24). Corticosteroid withdrawal/avoidance was not associated with acute rejection (odds ratio [OR], 0.87; P = 0.63), graft failure (OR, 0.45; P = 0.08), or death (OR, 0.34; P = 0.16) in renal trials. Conclusions: Corticosteroid withdrawal/avoidance in pediatric renal transplantation is associated with a significant improvement in height. Prepubertal patients appeared to have the greatest benefit. Importantly, the improvement in growth was not accompanied by increased rejection or worsening patient/allograft survival in the short term.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Kwun, Jean; Manook, Miriam; Page, Eugenia; Burghuber, Christopher; Hong, Jungjoo; Knechtle, Stuart J.
    Crosstalk Between T and B Cells in the Germinal Center After Transplantation
    imageAbstract: Crosstalk between B and T cells in transplantation is increasingly recognized as being important in the alloimmune response. T cell activation of B cells occurs by a 3-stage pathway, culminating with costimulation signals. We review the distinct T cell subtypes required for B-cell activation and discuss the formation of the germinal center (GC) after transplantation, with particular reference to the repopulation of the GC after depletional induction, and the subsequent effect of immunosuppressive manipulation of T cell-B cell interactions. In addition, ectopic GCs are seen in transplantation, but their role is not fully understood. Therapeutic options to target T cell-B cell interactions are of considerable interest, both as immunosuppressive tools, and to aid in the further understanding of these important alloimmune mechanisms.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Vanhove, Thomas; Goldschmeding, Roel; Kuypers, Dirk
    Kidney Fibrosis: Origins and Interventions
    imageAbstract: All causes of renal allograft injury, when severe and/or sustained, can result in chronic histological damage of which interstitial fibrosis and tubular atrophy are dominant features. Unless a specific disease process can be identified, what drives interstitial fibrosis and tubular atrophy progression in individual patients is often unclear. In general, clinicopathological factors known to predict and drive allograft fibrosis include graft quality, inflammation (whether “nonspecific” or related to a specific diagnosis), infections, such as polyomavirus-associated nephropathy, calcineurin inhibitors (CNI), and genetic factors. The incidence and severity of chronic histological damage have decreased substantially over the last 3 decades, but it is difficult to disentangle what effects individual innovations (eg, better matching and preservation techniques, lower CNI dosing, BK viremia screening) may have had. There is little evidence that CNI-sparing/minimization strategies, steroid minimization or renin-angiotensin-aldosterone system blockade result in better preservation of intermediate-term histology. Treatment of subclinical rejections has only proven beneficial to histological and functional outcome in studies in which the rate of subclinical rejection in the first 3 months was greater than 10% to 15%. Potential novel antifibrotic strategies include antagonists of transforming growth factor-β, connective tissue growth factor, several tyrosine kinase ligands (epidermal growth factor, platelet-derived growth factor, vascular endothelial growth factor), endothelin and inhibitors of chemotaxis. Although many of these drugs are mainly being developed and marketed for oncological indications and diseases, such as idiopathic pulmonary fibrosis, a number may hold promise in the treatment of diabetic nephropathy, which could eventually lead to applications in renal transplantation.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Pérez-Sáez, María José; Montero, Núria; Redondo-Pachón, Dolores; Crespo, Marta; Pascual, Julio
    Strategies for an Expanded Use of Kidneys From Elderly Donors
    imageAbstract: The old-for-old allocation policy used for kidney transplantation (KT) has confirmed the survival benefit compared to remaining listed on dialysis. Shortage of standard donors has stimulated the development of strategies aimed to expand acceptance criteria, particularly of kidneys from elderly donors. We have systematically reviewed the literature on those different strategies. In addition to the review of outcomes of expanded criteria donor or advanced age kidneys, we assessed the value of the Kidney Donor Profile Index policy, preimplantation biopsy, dual KT, machine perfusion and special immunosuppressive protocols. Survival and functional outcomes achieved with expanded criteria donor, high Kidney Donor Profile Index or advanced age kidneys are poorer than those with standard ones. Outcomes using advanced age brain-dead or cardiac-dead donor kidneys are similar. Preimplantation biopsies and related scores have been useful to predict function, but their applicability to transplant or refuse a kidney graft has probably been overestimated. Machine perfusion techniques have decreased delayed graft function and could improve graft survival. Investing 2 kidneys in 1 recipient does not make sense when a single KT would be enough, particularly in elderly recipients. Tailored immunosuppression when transplanting an old kidney may be useful, but no formal trials are available. Old donors constitute an enormous source of useful kidneys, but their retrieval in many countries is infrequent. The assumption of limited but precious functional expectancy for an old kidney and substantial reduction of discard rates should be generalized to mitigate these limitations.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Hoeksma, Dane; Rebolledo, Rolando A.; Hottenrott, Maximilia; Bodar, Yves S.; Wiersema-Buist, Janneke J.; Van Goor, Harry; Leuvenink, Henri G.D.
    Inadequate Antioxidative Responses in Kidneys of Brain-Dead Rats
    imageBackground: Brain death (BD)-related lipid peroxidation, measured as serum malondialdehyde (MDA) levels, correlates with delayed graft function in renal transplant recipients. How BD affects lipid peroxidation is not known. The extent of BD-induced organ damage is influenced by the speed at which intracranial pressure increases. To determine possible underlying causes of lipid peroxidation, we investigated the renal redox balance by assessing oxidative and antioxidative processes in kidneys of brain-dead rats after fast and slow BD induction. Methods: Brain death was induced in 64 ventilated male Fisher rats by inflating a 4.0F Fogarty catheter in the epidural space. Fast and slow inductions were achieved by an inflation speed of 0.45 and 0.015 mL/min, respectively, until BD confirmation. Healthy non–brain-dead rats served as reference values. Brain-dead rats were monitored for 0.5, 1, 2, or 4 hours, after which organs and blood were collected. Results: Increased MDA levels became evident at 2 hours of slow BD induction at which increased superoxide levels, decreased glutathione peroxidase (GPx) activity, decreased glutathione levels, increased inducible nitric oxide synthase and heme-oxygenase 1 expression, and increased plasma creatinine levels were evident. At 4 hours after slow BD induction, superoxide, MDA, and plasma creatinine levels increased further, whereas GPx activity remained decreased. Increased MDA and plasma creatinine levels also became evident after 4 hours fast BD induction. Conclusion: Brain death leads to increased superoxide production, decreased GPx activity, decreased glutathione levels, increased inducible nitric oxide synthase and heme-oxygenase 1 expression, and increased MDA and plasma creatinine levels. These effects were more pronounced after slow BD induction. Modulation of these processes could lead to decreased incidence of delayed graft function.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Kaths, J. Moritz; Echeverri, Juan; Chun, Yi Min; Cen, Jun Yu; Goldaracena, Nicolas; Linares, Ivan; Dingwell, Luke S.; Yip, Paul M.; John, Rohan; Bagli, Darius; Mucsi, Istvan; Ghanekar, Anand; Grant, David R.; Robinson, Lisa A.; Selzner, Markus
    Continuous Normothermic Ex Vivo Kidney Perfusion Improves Graft Function in Donation After Circulatory Death Pig Kidney Transplantation
    imageBackground: Donation after circulatory death (DCD) is current clinical practice to increase the donor pool. Deleterious effects on renal graft function are described for hypothermic preservation. Therefore, current research focuses on investigating alternative preservation techniques, such as normothermic perfusion. Methods: We compared continuous pressure-controlled normothermic ex vivo kidney perfusion (NEVKP) with static cold storage (SCS) in a porcine model of DCD autotransplantation. After 30 minutes of warm ischemia, right kidneys were removed from 30-kg Yorkshire pigs and preserved with 8-hour NEVKP or in 4°C histidine-tryptophan-ketoglutarate solution (SCS), followed by kidney autotransplantation. Results: Throughout NEVKP, electrolytes and pH values were maintained. Intrarenal resistance decreased over the course of perfusion (0 hour, 1.6 ± 0.51 mm per minute vs 7 hours, 0.34 ± 0.05 mm Hg/mL per minute, P = 0.005). Perfusate lactate concentration also decreased (0 hour, 10.5 ± 0.8 vs 7 hours, 1.4 ± 0.3 mmol/L, P < 0.001). Cellular injury markers lactate dehydrogenase and aspartate aminotransferase were persistently low (lactate dehydrogenase < 100 U/L, below analyzer range; aspartate aminotransferase 0 hour, 15.6 ± 9.3 U/L vs 7 hours, 24.8 ± 14.6 U/L, P = 0.298). After autotransplantation, renal grafts preserved with NEVKP demonstrated lower serum creatinine on days 1 to 7 (P < 0.05) and lower peak values (NEVKP, 5.5 ± 1.7 mg/dL vs SCS, 11.1 ± 2.1 mg/dL, P = 0.002). The creatinine clearance on day 4 was increased in NEVKP-preserved kidneys (NEVKP, 39 ± 6.4 vs SCS, 18 ± 10.6 mL/min; P = 0.012). Serum neutrophil gelatinase-associated lipocalin at day 3 was lower in the NEVKP group (1267 ± 372 vs 2697 ± 1145 ng/mL, P = 0.029). Conclusions: Continuous pressure-controlled NEVKP improves renal function in DCD kidney transplantation. Normothermic ex vivo kidney perfusion might help to decrease posttransplant delayed graft function rates and to increase the donor pool.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Zhu, Peng; Bailey, Stefanie R.; Lei, Biao; Paulos, Chrystal M.; Atkinson, Carl; Tomlinson, Stephen
    Targeted Complement Inhibition Protects Vascularized Composite Allografts From Acute Graft Injury and Prolongs Graft Survival When Combined With Subtherapeutic Cyclosporine A Therapy
    imageBackground: Recipients of vascularized composite allografts require aggressive and lifelong immunosuppression, and because the surgery is usually performed in nonlife-threatening situations, the development of strategies to minimize immunosuppression is especially pertinent for this procedure. We investigated how complement affects acute graft injury, alloimmunity, and immunosuppressive therapy. Methods: Vascularized composite allografts were transplanted from Balb/C to C57BL/6 mice that were complement deficient (C3 or double C3a Receptor (R)/C5aR), or treated with a targeted complement inhibitor (CR2-Crry). Allografts were analyzed for acute inflammation and injury, subacute T cell response, and survival in the absence and presence of cyclosporine A (CsA) therapy. Results: Allografts in C3-deficient or CR2-Crry–treated recipients were protected from skin and muscle ischemia-reperfusion injury (IRI). C3aR/C5aR-deficient recipients were more modestly protected. IgM and C3d colocalized within allografts from wild type and C3aR/C5aR-deficient recipients indicating IgM-mediated complement activation, and C3d deposition was almost absent in allografts from C3-deficient and CR2-Crry–treated recipients. Inflammatory cell infiltration and P-selectin expression was also significantly reduced in C3-deficient and CR2-Crry–treated recipients. Acute treatment with CR2-Crry or with 3 mg/kg per day CsA modestly, but significantly increased median allograft survival from 5.8 to 7.4 and 7.2 days, respectively. However, combined acute CR2-Crry treatment and CsA therapy increased mean graft survival to 17.2 days. Protection was associated with significantly reduced T cell infiltration of allografts and Tc1 cells in recipient spleens. Conclusions: Complement-mediated IRI augments graft allogenicity, and appropriate complement inhibition ameliorates IRI, decreases alloimmune priming and allows more immune-sparing CsA dosing.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Jucaud, Vadim; Ravindranath, Mepur H.; Terasaki, Paul I.
    Conformational Variants of the Individual HLA-I Antigens on Luminex Single Antigen Beads Used in Monitoring HLA Antibodies: Problems and Solutions
    imageBackground: Single antigen beads (SAB) are used for monitoring HLA antibodies in pretransplant and posttransplant patients despite the discrepancy between virtual and actual crossmatch results and transplant outcomes. This discrepancy can be attributed to the presence of conformational variants of HLA-I on SAB, assessment of which would increase the concordance between SAB and flow cytometry crossmatch (FCXM) results, thus enabling improved organ accessibility for the waiting list patients and a better prediction of antibody-mediated rejection. Methods: The conformational variants were examined on HLA-I beads, iBeads, acid-/alkali-treated beads, and T cells using HLA-I monoclonal antibodies (W6/32, TFL-006, and heavy chain (HC)-10). Results: The affinity of the monoclonal antibodies against HLA-I beads confirmed the presence and heterogeneous density of peptide-associated β2-microglobulin–associated HLA HC (pepA-β2aHC), peptide-free-β2aHC (pepF-β2aHC), and β2-free HC (β2fHC) on every single antigen-coated bead. In contrast, iBeads harbor a high density of pepA-β2aHC, low density of pepF-β2aHC, and are lacking β2fHC. The FCXM analyses confirmed the prevalence of pepA-β2aHC, but not pepF-β2aHC or β2fHC on resting T cells. Conclusions: The strength of a donor-specific antibody should be assessed with a bead-specific mean fluorescence intensity cutoff based on TFL-006 reactivity against HLA-I beads, and HC-10 against iBeads, where the β2fHC or pepF-β2aHC normalized donor-specific antibody level would reveal the true anti–pepA-β2aHC reactivity associated with positive FCXM.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Martens, Gregory R.; Reyes, Luz M.; Butler, James R.; Ladowski, Joseph M.; Estrada, Jose L.; Sidner, Richard A.; Eckhoff, Devin E.; Tector, Matt; Tector, A. Joseph
    Humoral Reactivity of Renal Transplant-Waitlisted Patients to Cells From GGTA1/CMAH/B4GalNT2, and SLA Class I Knockout Pigs
    imageBackground: Antipig antibodies are a barrier to clinical xenotransplantation. We evaluated antibody binding of waitlisted renal transplant patients to 3 glycan knockout (KO) pig cells and class I swine leukocyte antigens (SLA). Methods: Peripheral blood mononuclear cells from SLA identical wild type (WT), α1, 3-galactosyltransferase (GGTA1) KO, GGTA1/ cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) KO, and GGTA1/ CMAH /b1,4 N-acetylgalactosaminyl transferase (B4GalNT2) KO pigs were screened for human antibody binding using flow cytometric crossmatch (FCXM). Sera from 820 patients were screened on GGTA1/CMAH/B4GalNT2 KO cells and a subset with elevated binding was evaluated further. FCXM was performed on SLA intact cells and GGTA1/SLA class I KO cells after depletion with WT pig RBCs to remove cell surface reactive antibodies, but leave SLA antibodies. Lastly, human and pig reactive antibodies were eluted and tested for cross-species binding and reactivity to single-antigen HLA beads. Results: Sequential glycan KO modifications significantly reduce antibody binding of waitlisted patients. Sera exhibiting elevated binding without reduction after depletion with WT RBCs demonstrate reduced binding to SLA class I KO cells. Human IgG, eluted from human and pig peripheral blood mononuclear cells, interacted across species and bound single-antigen HLA beads in common epitope-restricted patterns. Conclusions: Many waitlisted patients have minimal xenoreactive antibody binding to the triple KO pig, but some HLA antibodies in sensitized patients cross-react with class I SLA. SLA class I is a target for genome editing in xenotransplantation.


    Date de mise en ligne : Jeudi 01 janvier 1970
    van Smaalen, Tim C.; Beurskens, Daniëlle M. H.; Hoogland, E. R. Pieter; Winkens, Bjorn; Christiaans, Maarten H. L.; Reutelingsperger, Chris P.; van Heurn, L. W. Ernest; Nicolaes, Gerry A. F.
    Presence of Cytotoxic Extracellular Histones in Machine Perfusate of Donation After Circulatory Death Kidneys
    imageBackground: Extracellular histones are cytotoxic molecules that are related to cell stress and death. They have been shown to play a crucial role in multiple pathophysiologic processes like sepsis, inflammation, vascular dysfunction, and thrombosis. Their role in organ donation and graft function and survival is still unknown. The aim of this study was to assess whether an association exists between the presence of extracellular histones in machine perfusates and deceased donor kidney viability. Methods: Machine perfusates of 390 donations after circulatory death kidneys were analyzed for histone concentration, and corresponding graft function and survival were assessed. Results: Extracellular histone concentrations were significantly higher in perfusates of kidneys with posttransplant graft dysfunction (primary nonfunction and delayed graft function) and were an independent risk factor for delayed graft function (odds ratio, 2.152; 95% confidence interval [95% CI], 1.199-3.863) and 1 year graft failure (hazard ratio, 1.386; 95% CI, 1.037-1.853), but not for primary nonfunction (odds ratio, 1.342; 95% CI, 0.900-2.002). One year graft survival was 12% higher in the group with low histone concentrations (P = 0.008) as compared with the group that contained higher histone concentrations. Conclusions: This study warrants future studies to probe for a possible role of cytotoxic extracellular histones in organ viability and suggests that quantitation of extracellular histones might contribute to assessment of posttransplant graft function and survival.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Parkes, Michael D.; Halloran, Philip F.; Hidalgo, Luis G.
    Evidence for CD16a-Mediated NK Cell Stimulation in Antibody-Mediated Kidney Transplant Rejection
    imageBackground: Natural killer (NK) cells localize in the microcirculation in antibody-mediated rejection (AMR) and have been postulated to be activated by donor-specific anti-HLA antibodies triggering their CD16a Fc receptors. However, direct evidence for NK cell CD16a triggering in AMR is lacking. We hypothesized that CD16a-inducible NK cell-selective transcripts would be expressed in human AMR biopsies and would offer evidence for CD16a triggering. Methods: We stimulated human NK cells through CD16a in vitro, characterized CD16a-inducible transcripts, and studied their expression in human kidney transplant biopsies with AMR and in an extended human cell panel to determine their selectivity. Results: In NK cells, CD16a stimulation induced increased expression of 276 transcripts (FC > 2x, false discovery rate < 0.05), including IFNG, TNF, CSF2, chemokines, such as CCL3, CCL4, and XCL1, and modulators of NK cell effector functions (TNFRSF9, CRTAM, CD160). Examination in an extended human cell panel revealed that CD160 and XCL1 were likely to be selective for NK cells in AMR. In biopsies, 8 of the top 30 CD16a-inducible transcripts were highly associated with AMR (P < 5 × 10−6): CCL4, CD160, CCL3, XCL1, CRTAM, FCRL3, STARD4, TNFRSF9. Other NK cell transcripts (eg, GNLY) were increased in AMR but not CD16a-inducible, their presence in AMR probably reflecting NK cell localization. Conclusions: The association of CD16a-inducible NK cell-selective transcripts CD160 and XCL1 with biopsies with AMR provides evidence for NK cell CD16a activation in AMR. This raises the possibility of other CD16a-triggered effects that are not necessarily transcriptional, including NK localization and cytotoxicity.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Smink, Alexandra M.; Li, Shiri; Hertsig, Don T.; de Haan, Bart J.; Schwab, Leendert; van Apeldoorn, Aart A.; de Koning, Eelco; Faas, Marijke M.; Lakey, Jonathan R.T.; de Vos, Paul
    The Efficacy of a Prevascularized, Retrievable Poly(D,L,-lactide-co-ε-caprolactone) Subcutaneous Scaffold as Transplantation Site for Pancreatic Islets
    imageBackground: The liver as transplantation site for human pancreatic islets is a harsh microenvironment for islets and it lacks the ability to retrieve the graft. A retrievable, extrahepatic transplantation site that mimics the pancreatic environment is desired. Ideally, this transplantation site should be located subdermal for easy surgical-access but this never resulted in normoglycemia. Here, we describe the design and efficacy of a novel prevascularized, subcutaneously implanted, retrievable poly (D,L-lactide-co-ε-caprolactone) scaffold. Method: Three dosages of rat islets, that is, 400, 800, and 1200, were implanted in immune compromised mice to test the efficacy (n = 5). Islet transplantation under the kidney capsule served as control (n = 5). The efficacy was determined by nonfasting blood glucose measurements and glucose tolerance tests. Results: Transplantation of 800 (n = 5) and 1200 islets (n = 5) into the scaffold reversed diabetes in respectively 80 and 100% of the mice within 6.8 to 18.5 days posttransplant. The marginal dose of 400 islets (n = 5) induced normoglycemia in 20%. The glucose tolerance test showed major improvement of the glucose clearance in the scaffold groups compared to diabetic controls. However, the kidney capsule was slightly more efficacious because all 800 (n = 5) and 1200 islets (n = 5) recipients and 40% of the 400 islets (n = 5) recipients became normoglycemic within 8 days. Removal of the scaffolds or kidney grafts resulted in immediate return to hyperglycemia. Normoglycemia was not achieved with 1200 islets in the unmodified skin group. Conclusions: Our findings demonstrate that the prevascularized poly (D,L-lactide-co-ε-caprolactone) scaffold maintains viability and function of islets in the subcutaneous site.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Di Zazzo, Antonio; Tahvildari, Maryam; Subbarayal, Brinda; Yin, Jia; Dohlman, Thomas H.; Inomata, Takenori; Mashaghi, Alireza; Chauhan, Sunil K.; Dana, Reza
    Proangiogenic Function of T Cells in Corneal Transplantation
    imageBackground: Corneal neovascularization increases the risk of T cell–mediated allograft rejection. Here, we investigate whether T cells promote angiogenesis in transplantation. Methods: Conventional effector T cells were collected from draining lymph nodes of allogeneic or syngeneic corneal transplanted BALB/c mice. T cells were either cocultured with vascular endothelial cells (VECs) to assess VEC proliferation or used in a mixed lymphocyte reaction assay. Messenger RNA (mRNA) expression of vascular endothelial growth factor (VEGF)-A, -C, and VEGF receptor 2 (VEGF-R2) in VECs was assessed by real-time PCR. VEGF-A protein expression was determined by enzyme-linked immunosorbent assay. Flow cytometry was used to analyze VEGF-R2 expression in corneal CD31+ cells, and VEGF-A and IFNγ expression in corneal CD4+ T cells. Results: Allogeneic T cells from high-risk (HR) grafted mice induced more VEC proliferation than those from syngeneic transplant recipients (P = 0.03). Vascular endothelial growth factor-A mRNA and protein expression were higher in T cells from draining lymph nodes (P = 0.03 and P = 0.04, respectively) and cornea (protein; P = 0.04) of HR compared with low-risk (LR) grafted hosts. Vascular endothelial growth factor-A, VEGF-C, and VEGF-R2 mRNA expression were increased in VECs when cocultured with T cells from HR transplants compared with LR transplants and naive mice. In addition, IFNγ blockade in T cell/VEC coculture increased VEC proliferation and VEGF-A protein expression, whereas blocking VEGF-A significantly reduced VEC proliferation (P = 0.04). Conclusions: Allogeneic T cells from corneal transplant hosts promote VEC proliferation, probably via VEGF-A signaling, whereas IFNγ shows an antiangiogenic effect. Our data suggest that T cells are critical mediators of angiogenesis in transplantation.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Gregori, Luisa; Serer, Arthur R.; McDowell, Kristy L.; Cervenak, Juraj; Asher, David M.
    Rapid Testing for Creutzfeldt-Jakob Disease in Donors of Cornea
    imageBackground: Creutzfeldt-Jakob disease (CJD) has been accidentally transmitted by contaminated corneal transplants. Eye donors are not ordinarily tested for CJD, in part because an easy test is not available. We propose a relatively simple postmortem procedure to collect brain samples without performing full autopsy and show that a test currently marketed for veterinary diagnosis would offer an effective screening test. Methods: We selected 6 brains from confirmed cases of human sporadic CJD and sampled each in triplicate (18 specimens), 28 control brains of individuals with non-CJD neurodegenerative diseases and 10 normal brains. We also applied a procedure involving retro-orbital puncture after enucleation and biopsied the frontal lobes and optic nerves of a macaque experimentally infected with variant CJD. All samples were tested with the IDEXX HerdChek BSE-Scrapie Ag Kit to detect the abnormal prion protein, PrPTSE. Results: The test discriminated between control and CJD-infected brains. All 18 infected brain samples diluted to 0.1%, except one, showed signals above cutoff, and a number of samples were reactive at even higher dilutions. These results suggest the test could detect the low concentrations of PrPTSE probably present in brains of donors at early stages of CJD. Our collection procedure obtained sufficient macaque brain and optic nerve tissues to detect PrPTSE. Conclusions: We showed that a commercial test combined with rapid sample collection might offer a practical solution to screen brains of cornea donors for evidence of CJD. Such a test might enhance safety of corneal transplants and some other tissue-derived products.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Lau, Lawrence; Kankanige, Yamuna; Rubinstein, Benjamin; Jones, Robert; Christophi, Christopher; Muralidharan, Vijayaragavan; Bailey, James
    Machine-Learning Algorithms Predict Graft Failure After Liver Transplantation
    imageBackground: The ability to predict graft failure or primary nonfunction at liver transplant decision time assists utilization of scarce resource of donor livers, while ensuring that patients who are urgently requiring a liver transplant are prioritized. An index that is derived to predict graft failure using donor and recipient factors, based on local data sets, will be more beneficial in the Australian context. Methods: Liver transplant data from the Austin Hospital, Melbourne, Australia, from 2010 to 2013 has been included in the study. The top 15 donor, recipient, and transplant factors influencing the outcome of graft failure within 30 days were selected using a machine learning methodology. An algorithm predicting the outcome of interest was developed using those factors. Results: Donor Risk Index predicts the outcome with an area under the receiver operating characteristic curve (AUC-ROC) value of 0.680 (95% confidence interval [CI], 0.669-0.690). The combination of the factors used in Donor Risk Index with the model for end-stage liver disease score yields an AUC-ROC of 0.764 (95% CI, 0.756-0.771), whereas survival outcomes after liver transplantation score obtains an AUC-ROC of 0.638 (95% CI, 0.632-0.645). The top 15 donor and recipient characteristics within random forests results in an AUC-ROC of 0.818 (95% CI, 0.812-0.824). Conclusions: Using donor, transplant, and recipient characteristics known at the decision time of a transplant, high accuracy in matching donors and recipients can be achieved, potentially providing assistance with clinical decision making.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Collett, David; Friend, Peter J.; Watson, Christopher J. E.
    Factors Associated With Short- and Long-term Liver Graft Survival in the United Kingdom: Development of a UK Donor Liver Index
    imageBackground: A measure of donor liver quality, the donor liver index, was developed and validated for the UK population of transplant recipients. Unlike previously proposed measures, this index is only based on variables that are available at the point of retrieval, and so does not include cold ischemic time. Methods: Indices of liver quality were based on data from the UK Transplant Registry on all 7929 liver transplants between January 2000 and December 2014. Results: The donor liver index (DLI) was based on factors shown to affect graft survival, which included donor age, sex, height, type (donor after brain death or circulatory death), bilirubin, smoking history, and whether the liver was split. A separate index (DLI1) looking at 1-year survival showed donor cardiac disease, black ethnicity, and steatosis to be additional risk factors. A strong association was found between DLI and whether or not a surgeon accepts an offered liver for transplant, with a marked fall in acceptance rates for livers with an index greater than 1.31. Since 2000, there has been a notable reduction in the quality of livers transplanted, coupled with variation between the 7 UK liver transplant centers in risk appetite. Conclusions: The DLI is an index of liver quality which enables analysis of the changing trends in liver quality and center behavior. DLI1 enables identification of factors affecting shorter-term survival, and perhaps identifies a cohort of livers that may benefit from novel preservation technologies.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Satapathy, Sanjaya K.; Vanatta, Jason M.; Helmick, Ryan A.; Flowers, Albert; Kedia, Satish K.; Jiang, Yu; Ali, Bilal; Eason, James; Nair, Satheesh P.; Ibebuogu, Uzoma N.
    Outcome of Liver Transplant Recipients With Revascularized Coronary Artery Disease: A Comparative Analysis With and Without Cardiovascular Risk Factors
    imageBackground: Coronary artery disease (CAD) is a significant problem during evaluation for liver transplantation (LT). We aim to assess survival in LT recipients based on presence, severity, extent of CAD, and cardiac events within 90 days of LT. Methods: Eighty-seven LT recipients with history of pre-LT angiogram (December 2005 to December 2012) were compared with 2 control groups without prior angiogram, 72 LT recipients matched for cardiovascular risk factors (control group I), and 119 consecutive LT recipients without any CV risk factors (control group II). CAD was assessed by (1) vessel score (≥50% reduction in luminal diameter), and (2) Extent score (Reardon scoring system). Results: Of the 87 LT recipients (study group), 58 (66.7%) had none or less than 50% stenosis, 29 (33.3%) had obstructive CAD (≥50% stenosis), 7 (8%) with single-vessel disease, and 22 (25.3%) with multivessel disease. In the study group, irrespective of prerevascularization severity of CAD (P = 0.357), number of segments involved (0, 1-2, > 2 segments, P = 0.304) and extent of CAD based on Reardon score (0, 1-9, >10, P = 0.224), comparable posttransplant survival was noted. Overall, patient survival in the revascularized CAD group was comparable to angiogram group without obstructive CAD, and both control group I and control group II (P = 0.184, Log Rank). Postoperative cardiac events within 90 days of LT predicted poor survival in study group as well as control groups. Conclusions: Severity or extent of CAD does not impact post-LT survival, if appropriately revascularized. Early postoperative cardiac events are associated with inferior survival in LT recipients, irrespective of underlying CAD.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Nicastro, Emanuele; Giovannozzi, Sara; Stroppa, Paola; Casotti, Valeria; Callegaro, Anna Paola; Tebaldi, Alessandra; Farina, Claudio; Colledan, Michele; D'Antiga, Lorenzo
    Effectiveness of Preemptive Therapy for Cytomegalovirus Disease in Pediatric Liver Transplantation
    imageBackground: Most pediatric liver transplantation (LT) centers administer long courses of prophylaxis against cytomegalovirus (CMV) without evidence of benefit and with significant drug exposure and costs. We aimed at evaluating overall outcomes, direct and putative indirect effects of CMV, possible impact of viremia and risk factors for CMV infection in pediatric LT recipients managed with ganciclovir-based preemptive therapy (PET). Methods: The records of all the children who underwent LT between 2008 and 2014 were retrospectively analyzed. Results: One hundred children were included. Three children had CMV disease; no CMV-related death or graft loss was recorded. The only identified risk factor for CMV infection was the donor/recipient serostatus (odds ratio, 17.23; 95% confidence interval, 1.88-157.87; P = 0.012), while viremia per se did not worsen LT outcomes, such as the incidence of acute rejection, Epstein-Barr virus infection, sepsis, biliary and vascular complications, nor graft dysfunction/loss or death at 3 and 5 years after LT. When compared with a historical cohort of children receiving ganciclovir prophylaxis, PET did not differ from prophylaxis for any of the selected outcomes, but was rather associated with lower antiviral drug exposure (6.4 ± 13 days vs 38.6 ± 14 days, P < 0.0001) and cost per patient (2.2 ± 3.9 k€ vs 6.6 ± 8.2 k€, P = 0.001). Conclusions: PET is effective in controlling CMV in children receiving LT, with lower costs and lower exposure to antivirals.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Freire, Maristela Pinheiro; Oshiro, Isabel C. V. S.; Pierrotti, Ligia C.; Bonazzi, Patricia R.; de Oliveira, Larissa M.; Song, Alice T. W.; Camargo, Carlos H.; van der Heijden, Inneke M.; Rossi, Flavia; Costa, Silvia F.; D'Albuquerque, Luiz A. C.; Abdala, Edson
    Carbapenem-Resistant Enterobacteriaceae Acquired Before Liver Transplantation: Impact on Recipient Outcomes
    imageBackground: Carbapenem-resistant Enterobacteriaceae (CRE) is an emergent microorganism of infections after liver transplant (LT). The aim of this study was to analyze the risk factors for CRE acquisition and infection after LT. Methods: This was a prospective cohort study involving patients who underwent LT in the 2010 to 2014 period. Surveillance cultures for CRE were collected immediately before LT and weekly thereafter until hospital discharge. Results: We analyzed 386 patients undergoing a total of 407 LTs. Before LT, 68 (17.6%) patients tested positive for CRE, 11 (16.2%) of those patients having CRE infection, whereas 119 (30.8%) patients acquired CRE after LT. Post-LT CRE infection was identified in 59 (15.7%) patients: Klebsiella pneumoniae was isolated in 83.2%; surgical site infection was the most common type of infection (46.7%). Multivariate analysis showed that post-LT dialysis was the only risk factor for post-LT CRE acquisition. Eighty-two percent of patients who underwent 3 or more post-LT dialysis sessions and acquired CRE before LT evolved with post-LT CRE infection. Other risk factors for CRE infection were acquisition of CRE post-LT, Model for End-Stage Liver Disease score greater than 32, combined transplantation, and reoperation. Patients who acquired CRE before LT had a high risk of developing CRE infection (P < 0.001). Conclusions: Measures for minimizing that risk, including altering the antibiotic prophylaxis, should be investigated and implemented.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Oliver, Joseph Benton; Marcus, Andrea Fleisch; Paster, Mark; Nespral, Joseph; Bongu, Advaith; Dikdan, George; Brown, Lloyd; Neidlinger, Nikole; Koneru, Baburao
    Organ Procurement Organization Survey of Practices and Beliefs Regarding Prerecovery Percutaneous Liver Biopsy in Donation After Neurologic Determination of Death
    imageBackground: Prerecovery liver biopsy (PLB) allows histological evaluation of the organ before procurement. The opinions and what factors might influence PLB use within Organ Procurement Organizations (OPOs) are unknown. Methods: A survey instrument was distributed by the Association of OPOs to the clinical directors of all 58 OPOs. Descriptive statistics were calculated. Results were also stratified based on OPO characteristics. Results: Forty-nine (84.5%) of 58 OPOs responded to the survey; 40 (81.6%) of 49 currently perform PLB. This did not vary based on land mass, population, livers discarded, transplanted, donor age, or recipient MELD scores. Donor age, obesity, alcohol abuse, hepatitis serology, liver only donor, imaging results, and transplant center request were the most common indications for PLB in over 80% of OPOs. The median rate of performance is 5% to 10% of donors. Most use interventional radiologists to perform and the donor hospital pathologist/s to interpret PLB. Most OPOs believe PLBs are safe, reliable, useful, and performed often enough. Most say they did not believe they are easy to obtain. Beliefs were mixed regarding accuracy. The topics likely to influence PLB use were utility and accuracy of PLB, and availability of staff to perform PLB. OPOs that perform PLB more often were more likely to have favorable opinions of safety and pathologist availability, and more influenced by safety, reliability, availability, and a national consensus on the use of PLB. Conclusions: Considerable variability exists in the use of PLB. Additional information on the utility, accuracy, and safety of PLB are needed to optimize its use.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Lanternier, Fanny; Amazzough, Karima; Favennec, Loic; Mamzer-Bruneel, Marie-France; Abdoul, Hendy; Tourret, Jérome; Decramer, Stéphane; Zuber, Julien; Scemla, Anne; Legendre, Christophe; Lortholary, Olivier; Bougnoux, Marie-Elisabeth; the ANOFEL Cryptosporidium National Network and Transplant Cryptosporidium Study Group
    Cryptosporidium spp. Infection in Solid Organ Transplantation: The Nationwide “TRANSCRYPTO” Study
    imageBackground: Diarrhea is a frequent complication of solid organ transplantation. Cryptosporidiosis is classically reported in patients with acquired immunodeficiency syndrome and emerged as a cause of persistent diarrhea in solid organ transplant patients. Methods: Through the ANOFEL Cryptosporidium National Network and the French Transplantation Society, we collected all cryptosporidiosis cases identified in solid organ transplanted patients between 2006 and 2010 in France. Results: We reported 47 solid organ transplant recipients (41 kidneys) with cryptosporidiosis, mostly men (68%), with a median age of 52 (6-70) years old. Five patients had additional immunodepression favoring cryptosporidiosis (CD40 ligand deficiency [n = 1], human immunodeficiency virus infection [n = 4]). Cryptosporidiosis occurred at a median time of 3.4 (0-19.8) years posttransplant. Exposure to environmental risk factors was found before infection onset in 18 patients. Time between first symptoms and diagnosis was 10 (2-110) days. Four patients had associated extraintestinal location (biliary tract [n = 3] and lung [n = 1]). Thirty-five patients received specific therapy against cryptosporidiosis ie nitozoxanide, 25 in monotherapy, and 10 in association with azithromycin, 13 in association with immunosuppression (IS) reduction. Four patients were cured with IS treatment tapering only. The others patients had neither IS reduction nor specific therapy against cryptosporidiosis. Cryptosporidiosis was complicated by renal failure in 15 patients. Symptoms resolved after a median of 10 days of treatment. Six patients relapsed and 3 died, 1 with evolutive infection. Conclusions: Cryptosporidiosis is a late posttransplant infection that disseminated to biliar duct or lung in 9% of patients. When limited to digestive tract, infection may resolve without IS reduction.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Serrano, Oscar Kenneth; Kerwin, Scott; Payne, William D.; Pruett, Timothy L.
    CD4 Count in HIV− Brain-Dead Donors: Insight into Donor Risk Assessment for HIV+ Donors
    imageBackground: The Human Immunodeficiency Virus (HIV) Organ Policy Equity Act allows for transplantation of organs from HIV-infected individuals (HIV+), provided it is performed under a research protocol. The safety assessment of an organ for transplantation is an essential element of the donation process. The risk for HIV-associated opportunistic infections increases as circulating CD4+ lymphocytes decrease to less than 200 cells/μL; however, the numbers of circulating CD4+ cells in the HIV-negative (HIV−) brain-dead donor (BDD) is not known. Methods: Circulating T-lymphocyte subset profiles in conventional HIV− BDD were measured in 20 BDD in a clinical laboratory. Results: The mean age of the BDD cohort was 48.7 years, 95% were white and 45% were women. The average body mass index was 29.2 kg/m2. Cerebrovascular accident (40%) was the most prevalent cause of death. Sixteen (80%) subjects had a CD4 count ≤441 cells/μL (lower limit of normal) and 11 (55%) had a CD4 count less than 200 cells/μL; 11 (55%) subjects had a CD8 count ≤125 cells/μL (lower limit of normal). CD4/CD8 ratio was below normal in 3 patients (normal, 1.4-2.6). No recipient had a recognized donor-associated adverse event. Conclusions: Absolute numbers of CD4 and CD8 T-lymphocytes are commonly reduced after brain death in HIV− individuals. Thus, CD4 absolute numbers are an inconsistent metric for assessing organ donor risk, irrespective of HIV status.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Wilk, Amber R.; Edwards, Leah B.; Edwards, Erick B.
    The Effect of Augmenting OPTN Data With External Death Data on Calculating Patient Survival Rates After Organ Transplantation
    imageBackground: Although the Organ Procurement and Transplantation Network (OPTN) database contains a rich set of data on United States transplant recipients, follow-up data may be incomplete. It was of interest to determine if augmenting OPTN data with external death data altered patient survival estimates. Methods: Solitary kidney, liver, heart, and lung transplants performed between January 1, 2011, and January 31, 2013, were queried from the OPTN database. Unadjusted Kaplan-Meier 3-year patient survival rates were computed using 4 nonmutually exclusive augmented datasets: OPTN only, OPTN + verified external deaths, OPTN + verified + unverified external deaths (OPTN + all), and an additional source extending recipient survival time if no death was found in OPTN + all (OPTN + all [Assumed Alive]). Pairwise comparisons were made using unadjusted Cox Proportional Hazards analyses applying Bonferroni adjustments. Results: Although differences in patient survival rates across data sources were small (≤1 percentage point), OPTN only data often yielded slightly higher patient survival rates than sources including external death data. No significant differences were found, including comparing OPTN + verified (hazard ratio [HR], 1.05; 95% confidence interval [95% CI], 1.00-1.10); P = 0.0356), OPTN + all (HR, 1.06; 95% CI, 1.01-1.11; P = 0.0243), and OPTN + all (Assumed Alive) (HR, 1.00; 95% CI, 0.96-1.05; P = 0.8587) versus OPTN only, or OPTN + verified (HR, 1.05; 95% CI, 1.00-1.10; P = 0.0511), and OPTN + all (HR, 1.05; 95% CI, 1.00-1.10; P = 0.0353) versus OPTN + all (Assumed Alive). Conclusions: Patient survival rates varied minimally with augmented data sources, although using external death data without extending the survival time of recipients not identified in these sources results in a biased estimate. It remains important for transplant centers to maintain contact with transplant recipients and obtain necessary follow-up information, because this information can improve the transplantation process for future recipients.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Ueno, Priscilla; Felipe, Claudia; Ferreira, Alexandra; Cristelli, Marina; Viana, Laila; Mansur, Juliana; Basso, Geovana; Hannun, Pedro; Aguiar, Wilson; Tedesco Silva, Helio Jr; Medina-Pestana, Jose
    Wound Healing Complications in Kidney Transplant Recipients Receiving Everolimus
    imageBackground: De novo use of mammalian target of rapamycin inhibitors after kidney transplantation is associated with a concentration-dependent incidence of wound healing adverse events (WHAE). The objective of this analysis was to compare the incidence of WHAE in patients receiving everolimus (EVR) or mycophenolate sodium (MPS). Methods: This was a predefined subanalysis of a single-center prospective randomized study in which 288 kidney transplant recipients receiving tacrolimus and prednisone were randomized for 3 different regimens: rabbit antithymocyte globulin (r-ATG)/EVR (N = 85); basiliximab (BAS)/EVR (N = 102); BAS/MPS (N = 101). Clinical WHAE were prospectively collected using a prespecified case report form in all study visits. Abdominal ultrasound was performed at 30 days posttransplant to capture subclinical abnormalities. Surgeons were blinded to randomized treatment and no specific surgical procedures were implemented. Results: A higher proportion of patients in BAS/EVR showed at least 1 clinical WHAE (22.3% vs 35.3% vs 22.0%, P = 0.03) and total clinical and subclinical WHAE (35% vs 42% vs 26%, P = 0.014) compared with BAS/MPS, respectively. A higher proportion of patients in r-ATG/EVR showed subclinical WHAE (13% vs 7% vs 4%, P = 0.025) compared with BAS/MPS, respectively. Patients receiving EVR showed a higher risk of developing clinical or subclinical WHAE (r-ATG/EVR vs BAS/MPS hazard ratio 1.30; BAS/EVR vs BAS/MPS hazard ratio 1.73, P = 0.028). Conclusions: In this cohort of de novo kidney transplant recipients receiving tacrolimus and prednisone, the use of EVR was associated with higher incidence of combined clinical and subclinical WHAE compared with MPS.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Lenihan, Colin R.; Montez-Rath, Maria E.; Winkelmayer, Wolfgang C.; Chang, Tara I.
    Drug-Eluting Stents Versus Bare Metal Stents for Percutaneous Coronary Intervention in Kidney Transplant Recipients
    imageBackground: The comparative effectiveness of percutaneous coronary intervention (PCI) with drug-eluting stents (DES) versus bare metal stents (BMS) has not been studied in the kidney transplant population. Methods: Using the US Renal Data System, we identified 3245 kidney transplant patients who underwent PCI between April 2003 and December 2010; 2400 and 845 patients received DES and BMS, respectively. We used propensity score matching and inverse probability of treatment weighting to create DES- and BMS-treated groups whose observed baseline characteristics were well-balanced. The associations between stent type and the outcomes of (1) death; (2) death or myocardial infarction (MI); (3) death, MI, or repeat revascularization (RR); and (4) hospitalized bleeding were compared using Cox proportional hazards regression. Results: Drug-eluting stent use increased during the study period, mirroring the trend described in the general population. In the propensity score-matched cohort, no significant association among DES (vs BMS) use and outcomes was observed at 1 and 2 years of follow-up. However, at 3 years, DES was associated with 20% (95% confidence interval [CI], 4-33%) lower risk of death, 15% (95% CI, 1-27%) lower risk of death or MI, and 14% (95% CI, 2-24%) lower risk of death, MI, or repeat revascularization. There were no significant differences in rates of hospitalized bleeding at any time point. Results were similar in the inverse probability of treatment weighting analysis. Conclusions: In this retrospective study of US kidney transplant recipients undergoing PCI, DES was associated with better clinical outcomes beyond 2 years of follow-up.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Dharnidharka, Vikas R.; Naik, Abhijit S.; Axelrod, David; Schnitzler, Mark A.; Xiao, Huiling; Brennan, Daniel C.; Segev, Dorry L.; Randall, Henry; Chen, Jiajing; Kasiske, Bertram; Lentine, Krista L.
    Clinical and Economic Consequences of Early Cancer After Kidney Transplantation in Contemporary Practice
    imageBackground: Current clinical and economic consequences of cancer after kidney transplantation are incompletely defined. Methods: We examined United States Renal Data System records of Medicare-insured kidney transplant recipients in 2000 to 2011 to determine clinical and economic impacts of cancer diagnosed within the first 3 years posttransplantation. Cancer diagnoses were identified using Medicare billing codes and categorized as nonmelanoma skin cancer (NMSC), viral-linked and “other” cancers. Associations of cancers with mortality and graft loss were estimated by time-varying Cox regression. Impacts of cancer diagnoses on inpatient and outpatient costs within each year were quantified by multivariate linear regression modeling. Results: Among 67 157 recipients, by 3 years posttransplant, NMSC was diagnosed in 5.7%, viral-linked cancer in 1.9%, and “other” cancers in 6.3%. Viral-linked cancer was associated with more than 3-fold increased risk in subsequent mortality until the third transplant anniversary, and nearly twice the mortality risk after year 3. “Other” cancers had similar associations with death and graft loss, whereas NMSC was associated with 33% higher mortality beyond the third year posttransplant. Viral-linked cancer had the largest inpatient and outpatient cost impacts per case, followed by “other” cancer, whereas NMSC impacted only outpatient costs. Care of new cancer diagnoses was generally more costly than care of previously established diagnoses. Cancer accounted for 3% to 5.5% of total inpatient Medicare expenditures and 1.5% to 3.3% of outpatient expenditures in the first 3 years posttransplant. Conclusions: Early posttransplant malignancy is an expensive and morbid condition that warrants attention in efforts to improve pretransplant screening and management protocols before and after transplant.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Ducroux, Emilie; Martin, Clemmie; Bouwes Bavinck, Jan Nico; Decullier, Evelyne; Brocard, Anabelle; Westhuis-van Elsäcker, Marlies E.; Lebbé, Céleste; Francès, Camille; Morelon, Emmanuel; Legendre, Christophe; Joly, Pascal; Kanitakis, Jean; Jullien, Denis; Euvrard, Sylvie; Dantal, Jacques
    Risk of Aggressive Skin Cancers After Kidney Retransplantation in Patients With Previous Posttransplant Cutaneous Squamous Cell Carcinomas: A Retrospective Study of 53 Cases
    imageBackground: The course of skin cancer after retransplantation in organ-transplant recipients who have already developed posttransplant skin cancer has not been assessed. Methods: This retrospective multicentric study included 53 patients with a history of cutaneous squamous cell carcinoma (SCC) after a first kidney transplantation who received a second kidney transplantation. The primary endpoint was the occurrence of aggressive cutaneous SCC after the second transplantation. Secondary endpoints included the course of skin cancers over 3 periods (first transplantation, return to dialysis, second transplantation), the time to occurrence, and risk factors for aggressive SCC after retransplantation. Results: The first SCC developed in 47 patients with a functional graft and in 6 after return to dialysis. After the first transplantation, 17 (33.3%) patients developed SCC in dialysis and 39 (73.6%) after the second transplantation, respectively. Twenty aggressive SCC developed over the study period. They occurred in 14 (26.4%) patients after retransplantation vs 5 (9.4%) after the first transplantation with a median delay of 50 months and were responsible for 5 deaths. Fair skin type, multiple tumors before retransplantation, treatment with azathioprine, T cell–depleting antibodies, and delayed revision of immunosuppression were associated with an increased risk of aggressive cutaneous SCC after retransplantation. Conclusions: Candidates to retransplantation with a history of posttransplant SCC have a high risk of aggressive SCC. Our data suggest that the risk could be reduced by a tailored immunosuppression. A wait period may be required depending on the clinicopathological characteristics of the previous SCC and discussed on an individual patient basis.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Jay, Colleen L.; Washburn, Kenneth; Dean, Patrick G.; Helmick, Ryan A.; Pugh, Jacqueline A.; Stegall, Mark D.
    Survival Benefit in Older Patients Associated With Earlier Transplant With High KDPI Kidneys
    imageBackground: Given high dialysis mortality rates for patients older than 60 years, accepting a kidney with a high Kidney Donor Profile Index (KDPI) score could enable earlier and potentially preemptive transplantation (preKT). However, evidence regarding the risks of high KDPI allografts in older patients is limited. Our objective was to determine the relative benefit for older patients of KDPI greater than 85% transplant either preemptively or not compared with remaining on the waitlist. Methods: United Network of Organ Sharing data from 2003 to 2012 for adult deceased donor kidney transplant candidates was analyzed to evaluate patient survival in patients older than 60 years for preKT and non-preKT KDPI greater than 85% transplants compared with candidates remaining on the waitlist including patients who received KDPI 0% to 85% transplants according to multivariate Cox regression models. Results: In the first year posttransplant for KDPI greater than 85% of transplants in recipients older than 60 years, preKT had a reduced mortality hazard (hazards ratio [HR], 0.61; 95% confidence interval [95% CI], 0.41-0.90) and non-preKT an increased mortality hazard (HR, 1.15; 95% CI, 1.03-1.27) compared with the waitlist including KDPI 0% to 85% transplant recipients. At 1 to 2 years and after 2 years, both KDPI greater than 85% groups had significant reductions in mortality (1-2 years: preKT HR, 0.38; 95% CI, [0.23-0.60] and non-preKT HR, 0.52; 95% CI, 0.45-0.61; and 2+ years: preKT HR, 0.50; 95% CI, 0.38-0.66 and non-preKT HR, 0.64; 95% CI, 0.58-0.70, respectively). Conclusions: PreKT and non-preKT KDPI greater than 85% transplant was associated with lower mortality hazard after the first year compared with the waitlist including KDPI 0% to 85% transplants in patients older than 60 years. Further consideration should be given to increased utilization of high KDPI grafts in older patients with the goal of avoiding or limiting time on dialysis.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Cheng, Elaine Y.; Everly, Matthew J.; Kaneku, Hugo; Banuelos, Nubia; Wozniak, Laura J.; Venick, Robert S.; Marcus, Elizabeth A.; McDiarmid, Suzanne V.; Busuttil, Ronald W.; Terasaki, Paul I.; Farmer, Douglas G.
    Prevalence and Clinical Impact of Donor-Specific Alloantibody Among Intestinal Transplant Recipients
    imageBackground: Rejection remains the leading cause of allograft loss, and a major barrier to improving long-term outcomes after intestinal transplantation. Our aim is to define the prevalence and investigate the role of donor-specific antibody (DSA) on intestinal graft outcomes. Methods: The study includes 109 transplants performed in 95 recipients at a single center. Patients were screened for DSA pretransplant, monitored regularly posttransplant and when clinically indicated using the single-antigen bead Luminex assay. Standard induction immunosuppression was with interleukin-2 receptor antagonists, and antithymocyte globulin in high-risk recipients. Maintenance regimens were tacrolimus-based. Results: Pretransplant DSA was detected in 12 (11%) recipients with 50% continuing to have circulating antibodies posttransplant. An additional 24 (25%) patients developed de novo DSA, and of these, 71% had persistent antibodies. Recipients with preformed DSA demonstrated elevated risks of early graft failure, whereas those with de novo DSA experienced accelerated graft loss once DSA was detected, reaching a 28% failure rate within 2 years. HLA-DQ mismatch is a significant risk factor for de novo DSA emergence, whereas the persistence of antibodies is predicted by DSA strength and specificity. Although inclusion of the liver in the intestinal allograft imparts an immunological advantage against rejection-related graft loss, this protective effect was lost among recipients with persistent DSA. Conclusions: The presence of DSA is associated with inferior graft outcomes among intestinal transplant recipients. An enhanced understanding of the mechanisms by which DSA causes allograft injury, and effective strategies targeting humoral immune reactivity are needed to improve long-term intestinal graft outcomes.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Kim, Irene K.; Choi, Jua; Vo, Ashley A.; Kang, Alexis; Patel, Mitasha; Toyoda, Mieko; Mirocha, James; Kamil, Elaine S.; Cohen, J. Louis; Louie, Sabrina; Galera, Odette; Jordan, Stanley C.; Puliyanda, Dechu P.
    Safety and Efficacy of Alemtuzumab Induction in Highly Sensitized Pediatric Renal Transplant Recipients
    imageBackground: Studies show that alemtuzumab, a potent lymphocyte-depleting agent, is well tolerated in pediatric renal transplantation. We report on the use of alemtuzumab induction in highly HLA sensitized (HS) pediatric kidney transplant patients. Methods: Fifty pediatric renal transplants were performed from 1/2009-12/2014. 15 HS patients received IVIG (2 g/kg ×2 doses)/rituximab (375 mg/m2 ×1) for desensitization with alemtuzumab induction (15-30 mg, 1 dose, subcutaneous), whereas 35 nonsensitized patients received anti–IL-2R. Graft survival and infections were compared between 2 groups. Results: All HS patients had received a prior transplant and were older with lower risk for viral infections due to serostatus. Patient survival was 100%, and graft outcomes were similar with mean 1-year creatinine of 1.03 ± 0.45 versus 0.99 ± 0.6 (P = 0.48). Although a higher incidence of acute cellular rejection was seen in HS patients receiving alemtuzumab (P = 0.001), there was a nonsignificant difference in antibody-mediated rejection. White blood cell and absolute lymphocyte count were significantly lower in alemtuzumab group at 30 days (P < 0.0001) and at 1 year (P = 0.026 and P = 0.001), respectively. There was no significant difference in bacterial, viral, or fungal infections after transplant. Conclusions: Alemtuzumab induction with desensitization led to nearly equivalent graft survival and functional outcomes in HS pediatric patients as nonsensitized patients receiving anti–IL-2R induction. With this small sample size, we observed significant reduction of white blood cell and absolute lymphocyte count up to 1 year posttransplant. The risk of infection was comparable between the 2 groups; however, patients who received alemtuzumab were older and at lower risk of viral infection due to serostatus.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Mucsi, Istvan; Bansal, Aarushi; Famure, Olusegun; Li, Yanhong; Mitchell, Margot; Waterman, Amy D.; Novak, Marta; Kim, S. Joseph
    Ethnic Background Is a Potential Barrier to Living Donor Kidney Transplantation in Canada: A Single-Center Retrospective Cohort Study
    imageBackground: We examined if African or Asian ethnicity was associated with lower access to kidney transplantation (KT) in a Canadian setting. Methods: Patients referred for KT to the Toronto General Hospital from January 1, 2003, to December 31, 2012, who completed social work assessment, were included (n = 1769). The association between ethnicity and the time from referral to completion of KT evaluation or receipt of a KT were examined using Cox proportional hazards models. Results: About 54% of the sample was white, 13% African, 11% East Asian, and 11% South Asian; 7% had “other” (n = 121) ethnic background. African Canadians (hazard ratio [HR], 0.75; 95% CI: 0.62-0.92]) and patients with “other” ethnicity (HR, 0.71; 95% CI, 0.55-0.92) were less likely to complete the KT evaluation compared with white Canadians, and this association remained statistically significant in multivariable adjusted models. Access to KT was significantly reduced for all ethnic groups assessed compared with white Canadians, and this was primarily driven by differences in access to living donor KT. The adjusted HRs for living donor KT were 0.35 (95% CI, 0.24-0.51), 0.27 (95% CI, 0.17-0.41), 0.43 (95% CI, 0.30-0.61), and 0.34 (95% CI, 0.20-0.56) for African, East or South Asian Canadians and for patients with “other” ethnic background, respectively. Conclusions: Similar to other jurisdictions, nonwhite patients face barriers to accessing KT in Canada. This inequity is very substantial for living donor KT. Further research is needed to identify if these inequities are due to potentially modifiable barriers.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Visentin, Jonathan; Guidicelli, Gwendaline; Taupin, Jean-Luc
    Conformational Variants of HLA-I Antigens on Luminex Single Antigen Beads
    imageNo abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Ravindranath, Mepur H.; Jucaud, Vadim
    The Authors' Reply
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Transplantation in Germany: Erratum
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Use of Everolimus in Liver Transplantation: Recommendations From a Working Group: Erratum
    No abstract available