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Les derniers abstracts de la revue Transplantation - Current Issue :


    Date de mise en ligne : Jeudi 01 janvier 1970
    Hafeez Bhatti, Abu Bakar; Saud Dar, Faisal
    Living Donor Liver Transplantation in Pakistan
    imageNo abstract available


    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
    Odorico, Jon S.
    Interspecies Organogenesis-Derived Tissues for Transplantation
    imageNo abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Johnson, Christian L.; Hutchinson, James A.
    Promote Your Work in Transplantation
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Heilman, Raymond L.; Green, Ellen P.; Reddy, Kunam S.; Moss, Adyr; Kaplan, Bruce
    Potential Impact of Risk and Loss Aversion on the Process of Accepting Kidneys for Transplantation
    imageAbstract: Behavioral economic theory suggests that people make decisions based on maximizing perceived value; however, this may be influenced more by the risk of loss rather than of potential gain. Additionally, individuals may seek certainty over uncertainty. These are termed loss aversion and risk aversion, respectively. Loss aversion is particularly sensitive to how the decision is “framed.” Thus, labeling a kidney as high Kidney Donor Profile Index results in higher discard rates because this creates a nonlinearity in perceived risk. There is also evidence that the perceived loss due to regulatory sanction results in increased organ discard rates. This may be due to the overuse of terminology that stresses regulatory sanctions and thus perpetuates fear of loss through a form of nudging. Our goal is to point out how these concepts of behavioral economics may negatively influence the decision process to accept these suboptimal organs. We hope to make the community more aware of these powerful psychological influences and thus potentially increase the utilization of these suboptimal organs. Further, we would urge regulatory bodies to avoid utilizing strategies that frame outcomes in terms of loss due to flagging and build models that are less prone to uncertain expected versus observed outcomes.


    Date de mise en ligne : Jeudi 01 janvier 1970
    White, Sarah L.
    Nudging the Organ Discard Problem
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Gabardi, Steven; van Gelder, Teun
    Causes and Consequences of the Worldwide Belatacept Shortage
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Abate, Davide
    The First 90 Days: Temporary Effect of Alemtuzumab on CMV Immune Reconstitution
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Wu, Christine M.; Hariharan, Sundaram
    A Simpler Blood Test for Monitoring Kidney Transplant Recipients: “A Disrupting Innovation”
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Bezinover, Dmitri
    The Use of Continuous Extended Criteria Graft Perfusion Will Lead to an Increase in Transplantable Organs
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    O'Connell, Philip J.; Kuypers, Dirk R.; Mannon, Roslyn B.; Abecassis, Michael; Chadban, Stephen J.; Gill, John S.; Murphy, Barbara; Nickerson, Peter W.; Schold, Jesse D.; Stock, Peter G.; Seron, Daniel; Alloway, Rita R.; Bromberg, Jonathan S.; Budde, Klemens; Jordan, Stanley C.; Legendre, Christophe; Lefaucheur, Carmen; Sarwall, Minnie; Segev, Dorry L.; Stegall, Mark D.; Tullius, Stefan G.; Wong, Germaine; Woodle, E Steve; Ascher, Nancy; Morris, Randall E.
    Clinical Trials for Immunosuppression in Transplantation: The Case for Reform and Change in Direction
    imageAbstract: Currently trials of immunosuppression in transplantation are in decline because their objectives remain focused on improving acute rejection rates and graft survival in the first 12 months. With 1 year renal graft survival rates of greater than 90% the best that can be hoped for is noninferiority trial outcomes compared with current standard of care. Current trial design is not leading to novel therapies improving long-term outcomes and safety, and hence important unmet clinical needs in transplantation remain unanswered. Issues that need to be addressed include but are not limited to: prevention of subclinical rejection in the first year, better 5- and 10-year graft outcomes, more effective treatment for high immunological risk and sensitized (including donor-specific antibody) patients, immunosuppressive combinations that are better tolerated by patients with fewer side effects and less morbidity and mortality. In September 2015, the Transplantation Society convened a group of transplant clinical trial experts to address these problems. The aims were to substantially realign the priorities of clinical trials for renal transplant immunosuppression with the current unmet needs and to propose new designs for clinical trials for transplant immunosuppression. Moving forward, the transplant community needs to provide trial data that will identify superior treatment options for patient subgroups and allow new agents to be evaluated for efficacy and safety and achieve timely regulatory approval. Trial designs for new transplant immunosuppression must be intelligently restructured to ensure that short- and long-term clinical outcomes continue to improve.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Brzostek, Joanna; Gascoigne, Nicholas R.J.
    Thymic Origins of T Cell Receptor Alloreactivity
    imageAbstract: Major histocompatibility complex (MHC) restriction is a unique feature of T cell antigen recognition. Mature T cells respond to antigenic nonself peptides bound to self-MHC molecules, but a sizeable fraction of peripheral T cells can also respond to nonself peptide-MHC (pMHC) complexes in the context of transplantation. MHC specificity of the T cell receptor (TCR) repertoire is shaped during thymic development. Two hypotheses have been proposed to explain MHC specificity of T cells. It has been suggested that MHC specificity is an intrinsic feature of TCR structure, mediated by the germline-encoded regions of the TCR sequence. In support of this model, an estimated 15% to 30% of preselection TCR repertoire is estimated to be MHC-specific. Moreover, structural studies have shown some degree of conserved binding topology for TCR-peptide MHC complexes. However, there is also evidence that MHC restriction can be imposed on the TCR repertoire during thymic development, and it has been proposed that the interaction of the Lck kinase with CD4 or CD8 coreceptors is critical for generation of MHC specificity. This review will discuss recent work on assessment of the preselection of TCR repertoire, molecular evidence for the germline encoded TCR bias for MHC, and for the coreceptor sequestration model in the context of alloreactivity and transplantation.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Jochmans, Ina; van Rosmalen, Marieke; Pirenne, Jacques; Samuel, Undine
    Adult Liver Allocation in Eurotransplant
    imageAbstract: Liver allocation in Eurotransplant is complex because allocation rules need to follow not only the guidelines of the European Commission but also the specific regulations of each of the 7 Eurotransplant countries with active liver transplant programs. Thirty-eight liver transplant centers served a population of about 135 million in 2015. Around 1600 deceased donor livers are transplanted annually. The number of deceased organ donors remains stable but donor age is increasing. Nevertheless, liver utilization rates are unchanged at around 80%. Donation after circulatory determination of death (DCD) increased fourfold in the past decade. In Belgium and the Netherlands, DCDs were responsible for 30% of deceased donor liver transplant activity in 2015; Austria only occasionally transplants a DCD liver; other Eurotransplant countries do not have active DCD programs. The most frequent indications for liver transplantation are alcoholic liver disease, hepatocellular carcinoma, and viral hepatitis. Livers are allocated first internationally to high urgency status patients or those with an approved combined organ status (for a liver in combination with heart, lung, intestine, or pancreas) and then on a national basis where allocation is recipient-driven or center-driven, depending on country-specific rules. Median waiting time for an elective liver transplant was 4,4 months in 2015; high urgency status patients waited a median of 2 days for a suitable liver. Mortality on the waiting list was 18% in 2015, 4% of patients were delisted because they became unfit for transplantation. One-year and 5-year risk unadjusted adult patient survival after transplantation is 80% and 65%, respectively.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Cooper, David K.C.; Wijkstrom, Martin; Hariharan, Sundaram; Chan, Joshua L.; Singh, Avneesh; Horvath, Keith; Mohiuddin, Muhammad; Cimeno, Arielle; Barth, Rolf N.; LaMattina, John C.; Pierson, Richard N. III
    Selection of Patients for Initial Clinical Trials of Solid Organ Xenotransplantation
    imageAbstract: Several groups have reported extended survival of genetically engineered pig organs in nonhuman primates, varying from almost 10 months for life-supporting kidney grafts and more than 2 years for non–life-supporting heart grafts to less than 1 month for life-supporting liver and lung grafts. We have attempted to define groups of patients who may not have an option to wait for an allograft. These include kidney, heart, and lung candidates who are highly-allosensitized. In addition, some kidney candidates (who have previously lost at least 2 allografts from rapid recurrence of native kidney disease) have a high risk of further recurrence and will not be offered a repeat allotransplant. Patients with complex congenital heart disease, who may have undergone previous palliative surgical procedures, may be unsuitable for ventricular assist device implantation. Patients dying of fulminant hepatic failure, for whom no alternative therapy is available, may be candidates for a pig liver, even if only as a bridge until an allograft becomes available. When the results of pig organ xenotransplantation in nonhuman primates suggest a realistic potential for success of a pilot clinical trial, highly selected patients should be offered participation.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Valenzuela, Nicole M.; Thomas, Kimberly A.; Mulder, Arend; Parry, Graham C.; Panicker, Sandip; Reed, Elaine F.
    Complement-Mediated Enhancement of Monocyte Adhesion to Endothelial Cells by HLA Antibodies, and Blockade by a Specific Inhibitor of the Classical Complement Cascade, TNT003
    imageBackground: Antibody-mediated rejection (AMR) of most solid organs is characterized by evidence of complement activation and/or intragraft macrophages (C4d + and CD68+ biopsies). We previously demonstrated that crosslinking of HLA I by antibodies triggered endothelial activation and monocyte adhesion. We hypothesized that activation of the classical complement pathway at the endothelial cell surface by HLA antibodies would enhance monocyte adhesion through soluble split product generation, in parallel with direct endothelial activation downstream of HLA signaling. Methods: Primary human aortic endothelial cells (HAEC) were stimulated with HLA class I antibodies in the presence of intact human serum complement. C3a and C5a generation, endothelial P-selectin expression, and adhesion of human primary and immortalized monocytes (Mono Mac 6) were measured. Alternatively, HAEC or monocytes were directly stimulated with purified C3a or C5a. Classical complement activation was inhibited by pretreatment of complement with an anti-C1s antibody (TNT003). Results: Treatment of HAEC with HLA antibody and human complement increased the formation of C3a and C5a. Monocyte recruitment by human HLA antibodies was enhanced in the presence of intact human serum complement or purified C3a or C5a. Specific inhibition of the classical complement pathway using TNT003 or C1q-depleted serum significantly reduced adhesion of monocytes in the presence of human complement. Conclusions: Despite persistent endothelial viability in the presence of HLA antibodies and complement, upstream complement anaphylatoxin production exacerbates endothelial exocytosis and leukocyte recruitment. Upstream inhibition of classical complement may be therapeutic to dampen mononuclear cell recruitment and endothelial activation characteristic of microvascular inflammation during AMR.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Usach, Vanina; Malet, Mariana; López, Margarita; Lavalle, Lucía; Piñero, Gonzalo; Saccoliti, María; Cueto, Alicia; Brumovsky, Pablo; Brusco, Alicia; Setton-Avruj, Patricia
    Systemic Transplantation of Bone Marrow Mononuclear Cells Promotes Axonal Regeneration and Analgesia in a Model of Wallerian Degeneration
    imageBackground: Reinnervation timing after nerve injury is critical for favorable axonal regeneration, remyelination, and clinical improvement. Considering bone marrow mononuclear cells (BMMC) are easily obtained and readily available for transplant, this work analyzed the effect of BMMC systemic administration on nerve repair and pain behavior. Methods: Adult rats with sciatic nerve crush were immediately and systemically injected BMMC through the caudal artery. Nontreated, sham and naïve rats were also included. Histological, immunohistochemical, biochemical, functional, and behavioral analyses were performed in nerves harvested from each group at different survival times. Results: Axons in BMMC-treated rats exhibited a more conserved morphological appearance than those in nontreated rats, as observed at different survival times both in semithin sections and ultrastructural analysis. BMMC-treated rats also showed a reduction in major myelin protein immunoreactive clusters 7 and 14 days postinjury, as compared with nontreated rats. Electrophysiological analysis showed BMMC treatment to slightly improve the amplitude of compound muscle action potential starting at 14 days postinjury. Finally, mechanical withdrawal threshold revealed a full preventive action against transient mechanical hypersensitivity in BMMC-treated rats. Conclusions: These data demonstrate the efficiency of BMMC, systemically and noninvasively transplanted, in correcting morphological, functional and behavioral alterations resulting from peripheral nerve injury.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Wu, Jingjing; Hu, Min; Qian, Yi Wen; Hawthorne, Wayne J.; Burns, Heather; Liuwantara, David; Alexander, Stephen I.; Yi, Shounan; O’Connell, Philip J.
    In Vivo Costimulation Blockade-Induced Regulatory T Cells Demonstrate Dominant and Specific Tolerance to Porcine Islet Xenografts
    imageBackground: Although islet xenotransplantation is a promising therapy for type 1 diabetes, its clinical application has been hampered by cellular rejection and the requirement for high levels of immunosuppression. The aim of this study was to determine the role of Foxp3+ regulatory T (Treg) cells in costimulation blockade–induced dominant tolerance to porcine neonatal islet cell cluster (NICC) xenografts in mice. Methods: Porcine-NICC were transplanted under the renal capsule of BALB/c or C57BL/6 recipients and given a single dose of CTLA4-Fc at the time of transplant and 4doses of anti-CD154 mAb to day 6. Depletion of Foxp3+Treg cell was performed in DEpletion of REGulatory T cells mice at day 80 posttransplantation. Foxp3+Treg cell from spleens of treated BALB/c mice (tolerant Treg cell), and splenocytes were cotransferred into islet transplanted nonobese diabetic background with severe combined immunodeficiency mice to assess suppressive function. Results: In treated mice, increased numbers of Foxp3+Treg cell were identified in the porcine-NICC xenografts, draining lymph node, and spleen. Porcine-NICC xenografts from treated mice expressed elevated levels of TGF-β, IL-10 and IFN-γ. Porcine-NICC xenograft tolerance was abrogated after depletion of Foxp3+Treg cell. Tolerant Treg cell produced high levels of IL-10 and had diverse T cell receptor Vβ repertoires with an oligoclonal expansion in CDR3 of T cell receptor Vβ14. These tolerant Treg cells had the capacity to transfer dominant tolerance and specifically exhibited more potent regulatory function to porcine-NICC xenografts that naive Treg cell. Conclusions: This study demonstrated that short-term costimulation blockade–induced dominant tolerance and that Foxp3+Treg cell played an essential role in its maintenance. Foxp3+Treg cells were activated and had more potent regulatory function in vivo than naive Treg cells.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Roberts, Veena; Campbell, Duncan J.; Lu, Bo; Chia, Joanne; Cowan, Peter J.; Dwyer, Karen M.
    The Differential Effect of Apyrase Treatment and hCD39 Overexpression on Chronic Renal Fibrosis After Ischemia-Reperfusion Injury
    imageBackground: Renal ischemia-reperfusion injury (IRI) leads to acute kidney injury and renal fibrosis. CD39 is a key purinergic enzyme in the hydrolysis of adenosine triphosphate (ATP) and increased CD39 enzymatic activity protects from acute IRI but its effect on renal fibrosis is not known. Methods: Using a mouse model of unilateral renal IRI, the effects of increased CD39 activity (using soluble apyrase and mice expressing human CD39 transgene) on acute and chronic renal outcomes were examined. Nucleotide (ATP, adenosine diphosphate, adenosine monophosphate) and nucleoside (adenosine and inosine) levels were quantified by high-performance liquid chromatography. Soluble apyrase reduced acute renal injury at 24 hours and renal fibrosis at 4 weeks post-IRI, compared with vehicle-treated mice. Results: Soluble apyrase reduced renal ATP, adenosine diphosphate, and adenosine monophosphate, but not adenosine levels, during ischemia. In comparison with wild-type littermates, hCD39 transgenic mice were protected from acute renal injury at 24 hours, but had increased renal fibrosis at 4 weeks post-IRI. hCD39 transgene expression was localized to the vascular endothelium at baseline and did not affect total renal nucleotide and nucleoside levels during ischemia. However, hCD39 transgene was more widespread at 4 weeks post-IRI and was associated with higher renal adenosine levels at 4 weeks post-IRI compared with wild-type littermates. Conclusions: A single dose of apyrase administration before IRI protects from both acute and chronic renal injuries and may have clinical application in protection from ischemic-induced renal injury. Furthermore, transgenic expression of hCD39 is associated with increased renal fibrosis after ischemia.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Li, Yakun; Ma, Dongxia; Wang, Zhimin; Yang, Jun
    MicroRNA-155 Deficiency in Kupffer Cells Ameliorates Liver Ischemia-Reperfusion Injury in Mice
    imageBackground: MicroRNA-155 (miR-155) is known to be involved in autoimmune diseases, inflammation, and transplantation. However, its role in a warm hepatic ischemia-reperfusion (IR) model has not been fully elucidated. Methods: Partial hepatic IR was performed in wild-type and miR-155–deficient mice treated with or without GdCl3, and then the serum transaminase concentration and histology were analyzed. Kupffer cells (KCs) were isolated from the liver after IR, and immunohistochemistry was used to evaluate activation and polarization. In addition, the mRNA concentrations of various inflammatory cytokines were measured. Macrophages were obtained from the abdominal cavity and challenged with or without lipopolysaccharide to determine the influence of miR-155 deficiency on macrophage polarization in vitro. Furthermore, we used in vitro coculture assays to determine the effect of miR-155 deficiency on hepatocyte apoptosis induced directly by KCs. Results: miR-155 deficiency ameliorated liver IR injury, and inhibition of KCs by GdCl3 abolished this protective effect. miR-155 deficiency decreased CD80, CD86, and major histocompatibility complex class II expression in KCs after IR and tipped the M1/M2 balance toward an anti-inflammatory profile, where proinflammatory cytokine secretion was suppressed and IL-10 was enhanced. In addition, hepatocyte apoptosis was reduced in coculture with miR-155–deficient KCs in vitro. Conclusions: miR-155 deficiency plays an effective role in attenuating liver IR injury likely by regulating the activation and inflammatory response, as well as modifying the polarization of KCs.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Compagnon, Philippe; Levesque, Eric; Hentati, Hassen; Disabato, Mara; Calderaro, Julien; Feray, Cyrille; Corlu, Anne; Cohen, José Laurent; Ben Mosbah, Ismail; Azoulay, Daniel
    An Oxygenated and Transportable Machine Perfusion System Fully Rescues Liver Grafts Exposed to Lethal Ischemic Damage in a Pig Model of DCD Liver Transplantation
    imageBackground: Control of warm ischemia (WI) lesions that occur with donation after circulatory death (DCD) would significantly increase the donor pool for liver transplantation. We aimed to determine whether a novel, oxygenated and hypothermic machine perfusion device (HMP Airdrive system) improves the quality of livers derived from DCDs using a large animal model. Methods: Cardiac arrest was induced in female large white pigs by intravenous injection of potassium chloride. After 60 minutes of WI, livers were flushed in situ with histidine-tryptophan-ketoglutarate and subsequently preserved either by simple cold storage (WI-SCS group) or HMP (WI-HMP group) using Belzer-MPS solution. Liver grafts procured from heart-beating donors and preserved by SCS served as controls. After 4 hours of preservation, all livers were transplanted. Results: All recipients in WI-SCS group died within 6 hours after transplantation. In contrast, the HMP device fully protected the liver against lethal ischemia/reperfusion injury, allowing 100% survival rate. A postreperfusion syndrome was observed in all animals of the WI-SCS group but none of the control or WI-HMP groups. After reperfusion, HMP-preserved livers functioned better and showed less hepatocellular and endothelial cell injury, in agreement with better-preserved liver histology relative to WI-SCS group. In addition to improved energy metabolism, this protective effect was associated with an attenuation of inflammatory response, oxidative load, endoplasmic reticulum stress, mitochondrial damage, and apoptosis. Conclusions: This study demonstrates for the first time the efficacy of the HMP Airdrive system to protect liver grafts from lethal ischemic damage before transplantation in a clinically relevant DCD model.


    Date de mise en ligne : Jeudi 01 janvier 1970
    DuBrock, Hilary M.; Goldberg, David S.; Sussman, Norman L.; Bartolome, Sonja D.; Kadry, Zakiyah; Salgia, Reena J.; Mulligan, David C.; Kremers, Walter K.; Kawut, Steven M.; Krowka, Michael J.; Channick, Richard N.
    Predictors of Waitlist Mortality in Portopulmonary Hypertension
    imageBackground: The current Organ Procurement Transplantation Network policy grants Model for End-Stage Liver Disease (MELD) exception points to patients with portopulmonary hypertension (POPH), but potentially important factors, such as severity of liver disease and pulmonary hypertension, are not included in the exception score, and may affect survival. The purpose of this study was to identify significant predictors of waitlist mortality in patients with POPH. Methods: We performed a retrospective cohort study of patients in the Organ Procurement and Transplantation Network database with hemodynamics consistent with POPH (defined as mean pulmonary arterial pressure >25 mm Hg and pulmonary vascular resistance [PVR] ≥240 dynes·s·cm−5) who were approved for a POPH MELD exception between 2006 and 2014. Using a Cox proportional hazards model, we identified predictors of waitlist mortality (or removal for clinical deterioration). Results: One hundred ninety adults were included. Age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.00-1.08; P = 0.0499), initial native MELD score (HR, 1.11; 95% CI, 1.05-1.17; P < 0.001), and initial PVR (HR, 1.12 per 100 dynes·s·cm−5; 95% CI, 1.02-1.23; P = 0.02) were the only significant univariate predictors of waitlist mortality and remained significant predictors in a multivariate model, which had a c-statistic of 0.71. PVR and mean pulmonary arterial pressure were not significant predictors of posttransplant mortality. Conclusions: Both the severity of liver disease and POPH (as assessed by MELD and PVR, respectively) were significantly associated with waitlist, but not posttransplant, mortality in patients with approved MELD exceptions for POPH. Both factors should potentially be included in the POPH MELD exception score to more accurately reflect waitlist mortality risk.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Ebel, Noelle H.; Hsu, Evelyn K.; Berry, Kristin; Horslen, Simon P.; Ioannou, George N.
    Disparities in Waitlist and Posttransplantation Outcomes in Liver Transplant Registrants and Recipients Aged 18 to 24 Years: Analysis of the UNOS Database
    imageBackground: We evaluated liver transplantation waitlist and posttransplantation outcomes in those aged 18 to 24 years compared with both younger (0-17 years) and older (25-34 years) registrants and recipients. Methods: Using national data from the United Network for Organ Sharing, competing risk, Cox regression and Kaplan-Meier analyses were performed on first-time liver transplant registrants (n = 13 979) and recipients (n = 8718) ages 0 to 34 years between 2002 and 2015. Results: Nonstatus 1A registrants, registrants aged 0 to 17 and 25 to 34 years were less likely to experience dropout from the waiting list compared with those aged 18 to 24 years (adjusted hazard ratio, 0-5 years = 0.36; 6-11 = 0.29; 12-17 = 0.48; 18-24 = 1.00; 25-34 = 0.82). Although there was no difference in risk of graft failure across all age groups, both younger and older age groups had significantly lower risk of posttransplant mortality compared with those aged 18 to 24 years (adjusted hazard ratio, for 0-5 years = 0.53, 6-11 = 0.48, 12-17 = 0.70, 18-24 = 1.00, 25-34 = 0.77). This may be related to lower likelihood of retransplantation after graft failure in those aged 18 to 24 years. Conclusions: This national registry study demonstrates for the first time poorer waitlist and postliver transplant outcomes in young adults ages 18 to 24 years at the time of listing and transplantation compared to older and younger age groups. Given the potential survival benefit in transplanting young adults and the shortage of solid organs for transplant, future studies are critical to identify and target modifiable risk factors to improve waitlist and long-term posttransplant outcomes in 18- to 24-year-old registrants and recipients.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Takahara, Takeshi; Wakabayashi, Go; Nitta, Hiroyuki; Hasegawa, Yasushi; Katagiri, Hirokatsu; Umemura, Akira; Takeda, Daiki; Makabe, Kenji; Otsuka, Koki; Koeda, Keisuke; Sasaki, Akira
    The First Comparative Study of the Perioperative Outcomes Between Pure Laparoscopic Donor Hepatectomy and Laparoscopy-Assisted Donor Hepatectomy in a Single Institution
    imageBackground: In a statement from the second International Consensus Conference for Laparoscopic Liver Resection, adult-to-adult laparoscopic donor surgery was the earliest phase of development. It was recommended that the procedure be performed under institutional ethical approval and a reporting registry. Method: At our institute, we started laparoscopy-assisted donor hepatectomy (LADH) in 2007 and changed to pure laparoscopic donor hepatectomy (PLDH) in 2012. This study included 40 living donors who underwent LADH and 14 live donors who underwent PLDH. We describe the technical aspects and outcomes of our donor hepatectomy from assist to pure and examine the liver allograft outcomes of the recipients after LADH and PLDH. Results: There was significantly less blood loss in the PLDH group (81.07 ± 52.78 g) than that in the LADH group (238.50 ± 177.05 g), although the operative time was significantly longer in the PLDH group (454.93 ± 85.60 minutes) than in the LADH group (380.40 ± 44.08 minutes). And there were no significant differences in postoperative complication rate in the 2 groups. The liver allograft outcomes were acceptable and comparable with open living donor hepatectomy. Conclusions: By changing our routine approach from assist to pure, PLDH can be performed safely, with better exposure due to magnification, and with less blood loss under pneumoperitoneal pressure. PLDH, which has become our promising donor procedure, results in less blood loss, better cosmesis, and the donor’s complete rehabilitation without deterioration in donor safety.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Bruinsma, Bote G.; Avruch, James H.; Sridharan, Gautham V.; Weeder, Pepijn D.; Jacobs, Marie Louise; Crisalli, Kerry; Amundsen, Beth; Porte, Robert J.; Markmann, James F.; Uygun, Korkut; Yeh, Heidi
    Peritransplant Energy Changes and Their Correlation to Outcome After Human Liver Transplantation
    imageBackground: The ongoing shortage of donor livers for transplantation and the increased use of marginal livers necessitate the development of accurate pretransplant tests of viability. Considering the importance energy status during transplantation, we aimed to correlate peritransplant energy cofactors to posttransplant outcome and subsequently model this in an ex vivo setting. Methods: Sequential biopsies were taken from 19 donor livers postpreservation, as well as 30 minutes after portal venous reperfusion and hepatic arterial reperfusion and analyzed by liquid chromatography-mass spectrometry for energetic cofactors (adenosine triphosphate [ATP]/adenosine diphosphate [ADP]/adenosine monophosphate [AMP], nicotinamide adenine dinucleotide /NAD+, nicotinamide adenine dinucleotide phosphate / nicotinamide adenine dinucleotide phosphate +, flavin adenine dinucleotide +, glutathione disulfide/glutathione). Energy status was correlated to posttransplant outcome. In addition, 4 discarded human donation after circulatory death livers were subjected to ex vivo reperfusion, modeling reperfusion injury and were similarly analyzed for energetic cofactors. Results: A rapid shift toward higher energy adenine nucleotides was observed following clinical reperfusion, with a 2.45-, 3.17- and 2.12-fold increase in ATP:ADP, ATP:AMP and energy charge after portal venous reperfusion, respectively. Seven of the 19 grafts developed early allograft dysfunction. Correlation with peritransplant cofactors revealed a significant difference in EC between early allograft dysfunction and normal functioning grafts (0.09 vs 0.31, P < 0.05). In the simulated reperfusion model, a similar trend in adenine nucleotide changes was observed. Conclusions: A preserved energy status appears critical in the peritransplant period. Levels of adenine nucleotides change rapidly after reperfusion and ratios of ATP/ADP/AMP after reperfusion are significantly correlated to graft function. Using these markers as a viability test in combination with ex vivo reperfusion may provide a useful predictor of outcome that incorporates donor, preservation, and reperfusion factors.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Konerman, Monica A.; Fritze, Danielle; Weinberg, Richard L.; Sonnenday, Christopher J.; Sharma, Pratima
    Incidence of and Risk Assessment for Adverse Cardiovascular Outcomes After Liver Transplantation: A Systematic Review
    imageBackground: Cardiovascular events represent a major source of morbidity and mortality after liver transplantation and will likely increase given the aging population and nonalcoholic fatty liver disease as a leading indication for transplant. The optimal cardiovascular risk stratification approach in this evolving patient population remains unclear. The aims of this systematic review are to: (1) refine the definition, (2) characterize the incidence, and (3) identify risk factors for cardiovascular events post-liver transplantation. Additionally, we evaluated performance characteristics of different cardiac testing modalities. Methods: MEDLINE via PubMed, EMBASE, Web of Science, and Scopus were searched for studies published between 2002 and 2016 (model of end-stage liver disease era). Two authors independently reviewed articles to select eligible studies and performed data abstraction. Results: Twenty-nine studies representing 57 493 patients from 26 unique cohorts were included. Definitions of cardiovascular outcomes were highly inconsistent. Incidence rates were widely variable: 1% to 41% for outcomes of 6 months or shorter and 0% to 31% for outcomes longer than 6 months. Multivariate analyses demonstrated that older age and history of cardiac disease were the most consistent predictors of cardiovascular events posttransplant (significant in 8/23 and 7/22, studies, respectively). Predictive capacity of various cardiac imaging modalities was also discrepant. Conclusions: The true incidence of cardiovascular outcomes post-liver transplant remains unknown in large part due to lack of consensus regarding outcome definition. Overall, poor data quality and gaps in knowledge limit the ability to clearly identify predictors of outcomes, but existing data support a more aggressive risk stratification protocol for patients of advanced age and/or with preexisting cardiac disease.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Badenoch, Adam; Sharma, Anand; Gower, Simon; Selzner, Markus; Srinivas, Coimbatore; Wasowicz, Marcin; McCluskey, Stuart A.
    The Effectiveness and Safety of Tranexamic Acid in Orthotopic Liver Transplantation Clinical Practice: A Propensity Score Matched Cohort Study
    imageBackground: Randomized trials have demonstrated the efficacy of tranexamic acid (TXA) in reducing blood loss and transfusion requirements during liver transplantation. However, clinical utilization is limited due to a perceived lack of generalizable effectiveness and concerns regarding its thromboembolic risks. The aim of this study was to describe the clinical use of TXA and to provide a pragmatic reappraisal of its effectiveness and safety. Methods: After ethics approval, data were collected from 1799 consecutive liver transplant recipients between January 1, 2002, and December 31, 2015, using retrospectively collected electronic databases. Propensity matching was used to account for confounders of transfusion and thrombotic risk. Exposure was defined as a total TXA dose greater than 10 mg/kg for 50% of the operative duration. Results: After propensity matching, 367 unique pairs were well balanced in terms of all measured covariates. In the matched pairs, patients exposed to TXA received less red blood cell (3 [0, 6] vs 4 [1, 7] P = 0.003) and frozen plasma (6 [2, 10] vs 6 [2, 12], P = 0.032) transfusions. There were no differences in thromboembolic events between the groups (22 [6.0%] vs 36 [9.8%]). Conclusions: TXA appears effective in reducing red blood cell transfusion requirements without increasing the risk of thromboembolic events across a wide variety of liver transplant recipients, including those at low risk of bleeding or high risk of thromboembolic complications. We did not detect evidence of an increased risk of thrombotic complications with TXA exposure.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Volk, Michael L.; Wilk, Amber R.; Wolfe, Cameron; Kaul, Daniel R.
    The “PHS Increased Risk” Label Is Associated With Nonutilization of Hundreds of Organs per Year
    imageBackground: The Public Health Service “Increased Risk” (PHS IR) designation identifies donors at increased risk of transmitting hepatitis B, C, and human immunodeficiency virus. Although the risk remains very low in the era of nucleic acid testing, we hypothesized that this label may result in decreased organ utilization. Methods: Organ Procurement and Transplantation Network data were used to compare utilization rates between PHS-IR and non–PHS-IR donors, as well as to compare export rates and variation in utilization. Results: Among adult standard criteria donors between 2010 and 2013 with a known PHS-IR status, covariate-adjusted utilization rates were lower among PHS-IR donors than non–PHS-IR donors for all organs. For example, 4073 (76.7%) of 5314 PHS-IR kidneys were used, compared with 25 490 (83.7%) of 30 456 non–PHS-IR kidneys—an absolute difference of 7%. Furthermore, all PHS-IR organs had higher export rates than non–PHS-IR organs. For example, 28.7% of PHS-IR kidneys were exported versus 19.7% of non–PHS-IR kidneys. Finally, the utilization rate of PHS-IR organs varied by Donation Service Area; utilization ranged from 20% to 100% among adult kidneys, suggesting significant variation in practices. Similar patterns were seen among pediatric donors. Based on the covariate-adjusted model, if the PHS-IR label did not exist, there could be an additional 313 transplants performed in the United States each year. Conclusions: The PHS “increased risk” label appears to be associated with nonutilization of hundreds of organs per year, despite the very low risk of disease transmission. Better tools are needed to communicate the magnitude of risk to patients and their families.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Pruett, Timothy L.; Clark, Marissa A.; Taranto, Sarah E.
    Deceased Organ Donors and PHS Risk Identification: Impact on Organ Usage and Outcomes
    imageBackground: In 2013, the public health service (PHS) changed the criteria intended to identify organ donors that put the associated organ recipients at increased risk for acquiring human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). The changing donor demographics, organ utilization, and outcomes associated with this change are not known. Methods: A review of the Organ Procurement and Transplantation Network database was performed to assess the impact of PHS donor designation on organ utilization and outcomes. Results: After the 2013 modification, over 20% of all deceased organ donors in the United States were identified as PHS increased risk. Compared with the standard risk deceased organ donor, the PHS donor was younger, male, died from anoxia, more likely to be HCV and antibody reacting to hepatitis B core antigen+, and less likely to have diabetes or hypertension. Organs from the 18- to 34-year-old deceased donors with PHS risks (but relatively few medical comorbidities) and tested negative for HCV were less frequently transplanted compared with the standard risk donors (3.9 vs 4.2 organs transplanted per donor). However, the transplant patient and graft survival as well as risk of unexpected transmission of HIV, HBV, and HCV were equivalent, irrespective of PHS donor status. Conclusions: The rationale of using PHS donor designation that negatively impacts utilization of high-quality organs without the benefit of identifying the subset of organs with demonstrable proclivity to transmit HIV, HBV, or HCV needs to be reexamined.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Trotter, Patrick B.; Summers, Dominic M.; Robb, Matthew; Hulme, William; Ushiro-Lumb, Ines; Watson, Christopher J.E.; Neuberger, James; Bradley, J. Andrew
    Deceased Organ Donors With a History of Increased Risk Behavior for the Transmission of Blood-Borne Viral Infection: The UK Experience
    imageBackground: Deceased organ donors are routinely screened for behaviors that increase the risk of transmissible blood-borne viral (BBV) infection, but the impact of this information on organ donation and transplant outcome is not well documented. Our aim was to establish the impact of such behavior on organ donation and utilization, as well transplant recipient outcomes. Methods: We identified all UK deceased organ donors from 2003 to 2015 with a disclosed history of increased risk behavior (IRB) including intravenous drug use (IVDU), imprisonment and increased risk sexual behavior. Results: Of 17 262 potential donors, 659 (3.8%) had IRB for BBV and 285 (1.7%) were seropositive for BBV, of whom half had a history of IRB (mostly IVDU [78.5%]). Of actual donors with IRB, 393 were seronegative for viral markers at time of donation. A history of recent IVDU was associated with fewer potential donors proceeding to become actual organ donors (64% vs 75%, P = 0.007). Donors with IRB provided 1091 organs for transplantation (624 kidneys and 467 other organs). Transplant outcome was similar in recipients of organs from donors with and without IRB. There were 3 cases of unexpected hepatitis C virus transmission, all from an active IVDU donor who was hepatitis C virus seronegative at time of donation, but was found to be viremic on retrospective testing. Conclusions: Donors with a history of IRB provide a valuable source of organs for transplantation with good transplant outcomes and there is scope for increasing the use of organs from such donors.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Marrero, Wesley J.; Naik, Abhijit S.; Friedewald, John J.; Xu, Yongcai; Hutton, David W.; Lavieri, Mariel S.; Parikh, Neehar D.
    Predictors of Deceased Donor Kidney Discard in the United States
    imageBackground: Renal transplantation is a lifesaving intervention for end-stage renal disease. The demand for renal transplantation outweighs the availability of organs; however, up to 20% of recovered kidneys are discarded before transplantation. We aimed to better characterize the risk factors for deceased donor kidney discard. Methods: We performed a secondary analysis of the Organ Procurement and Transplantation Network database from 2000 to 2012 of all solid organ donors. The cohort was split into training (80%) and validation (20%) subsets. We performed a stepwise logistic regression to develop a multivariate risk prediction model for kidney graft discard and validated the model. The performance of the models was evaluated with respect to calibration, and area under the curve (AUC) of receiver operating characteristic curves. Results: There were no significant baseline differences between the training (n = 57 474) and validation (n = 14 368) cohorts. The multivariate model validation showed very good discriminant function in predicting kidney discard (AUC = 0.84). Predictors of increased discard included age older than 50 years, performance of a kidney biopsy, cytomegalovirus seropositive status, donation after cardiac death, hepatitis B and C seropositive status, cigarette use, diabetes, hypertension, terminal creatinine greater than 1.5 mg/dL and AB blood type. The model outperformed the Kidney Donor Risk Index in predicting discard (P < 0.001). Subgroup analysis of expanded criteria donor kidneys demonstrated good discrimination with an AUC of 0.70. Conclusions: We have characterized several important predictors of deceased donor kidney discard. Better understanding of factors that lead to increased deceased donor kidney discard can allow for targeted interventions to reduce discard.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Mittal, Shruti; Adamusiak, Anna; Horsfield, Catherine; Loukopoulos, Ioannis; Karydis, Nikolaos; Kessaris, Nicos; Drage, Martin; Olsburgh, Jonathon; Watson, Christopher JE; Callaghan, Chris J.
    A Re-evaluation of Discarded Deceased Donor Kidneys in the UK: Are Usable Organs Still Being Discarded?
    imageBackground: A significant proportion of procured deceased donor kidneys are subsequently discarded. The UK Kidney Fast-Track Scheme (KFTS) was introduced in 2012, enabling kidneys at risk of discard to be simultaneously offered to participating centers. We undertook an analysis of discarded kidneys to determine if unnecessary organ discard was still occurring since the KFTS was introduced. Methods: Between April and June 2015, senior surgeons independently inspected 31 consecutive discarded kidneys from throughout the United Kingdom. All kidneys were biopsied. Organs were categorized as usable, possibly usable pending histology, or not usable for implantation. After histology reports were available, final assessments of usability were made. Results: There were 19 donors (6 donations after brain death, 13 donations after circulatory death), with a median (range) donor age of 67 (29-83) years and Kidney Donor Profile Index of 93 (19-100). Reasons for discard were variable. Only 3 discarded kidneys had not entered the KFTS. After initial assessment postdiscard, 11 kidneys were assessed as usable, with 9 kidneys thought to be possibly usable. Consideration of histological data reduced the number of kidneys thought usable to 10 (10/31; 32%). Conclusions: The KFTS scheme is successfully identifying organs at high risk of discard, though potentially transplantable organs are still being discarded. Analyses of discarded organs are essential to identify barriers to organ utilization and develop strategies to reduce unnecessary discard.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Lubetzky, Michelle; Chun, Soohwan; Joelson, Andrew; Coco, Maria; Kamal, Layla; Ajaimy, Maria; Gaglio, Paul; Akalin, Enver; De Boccardo, Graciella
    Safety and Efficacy of Treatment of Hepatitis C in Kidney Transplant Recipients With Directly Acting Antiviral Agents
    imageBackground: With the development of all oral, interferon-free directly acting antiviral (DAA) medications, treatment of hepatitis C virus (HCV) infection in renal transplant recipients is possible, but limited data exists on its safety and efficacy. Methods: We performed a retrospective cohort analysis of patients transplanted at our center with HCV who have been started on DAAs. Primary endpoints included sustained virologic response as defined as negative viral load at 12 weeks postcompletion of therapy and allograft function. Results: A total of 31 patients met inclusion criteria. The most commonly used regimen was sofosbuvir and ledipasvir (n = 21). Of the treated patients, 100% had undetectable viral load at the completion of therapy. Of the 31 patients treated, 30 (97%) achieved sustained virologic response. Both graft and patient survivals at most recent follow-up was 100%. There was no significant change in glomerular filtration rate (GFR) before or after therapy (64.2 ± 16.5 mL/min per body surface area before vs. 58.9 ± 17.5 mL/min per body surface area after therapy; P = 0.22); however, 3 patients now have GFR less than 20. A total of 6 (19.3%) of 31 patients had worsening proteinuria during or shortly after therapy. Patients with more than 500 mg/g of proteinuria at the start of treatment were significantly more likely to develop worsening proteinuria than those with less than 500 mg/g of proteinuria at the start of therapy (P < 0.001). Retrospective review of 20 untreated HCV patients did not demonstrate worsening allograft function and proteinuria during a median follow-up time of 1386 days (range, 332–6254). Conclusions: Our preliminary data demonstrate that DAAs can be used safely and effectively in patients after kidney transplantation. Patients with proteinuria or lower GFR should be monitored more closely.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Midtvedt, Karsten; Bergan, Stein; Reisæter, Anna Varberg; Vikse, Bjørn Egil; Åsberg, Anders
    Exposure to Mycophenolate and Fatherhood
    imageBackground: Mycophenolic acid (MPA) is the active immunosuppressive substance in both mycophenolate mofetil and mycophenolate sodium, and it is widely used after organ transplantation. In women, taking MPA is teratogenic and may also influence spermatogenesis. There is a lack of knowledge regarding outcome of pregnancies fathered by men exposed to MPA. Methods: We compared outcomes in pregnancies fathered by renal transplant men per whether they had been exposed to MPA or not at time of conception. A nationwide population-based retrospective cohort study was performed. Data from the Norwegian Renal Registry with all renal transplanted men alive between January 1, 1995 and December 31, 2015 were included, and relevant outcome data were extracted from the Medical Birth Registry of Norway. Results: During the given time, 230 immunosuppressed renal transplanted men fathered 350 children (155 on MPA/195 not on MPA). There were no significant increased risks of malformation (3.9% vs. 2.6%, P = 0.49) in MPA exposed versus unexposed cohorts of children. The average dose (±SD) of mycophenolate was 1.42 ± 0.3 g/day and the individual median MPA trough concentration in the time period of anticipated conception and pregnancy was 2.8 ± 1.6 mg/L. Birth weight was similar in exposed and unexposed cohorts of children; 3381 ± 681 g vs. 3429 ± 714 g (P = 0.53). Conclusions: Paternal exposure to MPA did not increase the risk of adverse birth outcomes in children fathered by male kidney transplanted patients. These results are reassuring and support the continuation of paternal MPA treatment before, during, and after conception.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Chung, Byung Ha; Kim, Bo-Mi; Doh, Kyoung Chan; Min, Ji-Won; Cho, Mi-La; Kim, Kyoung Woon; Yang, Chul Woo
    Suppressive Effect of 1α,25-Dihydroxyvitamin D3 on Th17-Immune Responses in Kidney Transplant Recipients With Tacrolimus-Based Immunosuppression
    imageBackground: The aim of this study was to investigate whether 1α,25-dihydroxyvitamin D3 can regulate Th17-related immune responses in kidney transplant recipients (KTRs) being treated with tacrolimus (Tac)-based immunosuppression. Methods: First, we evaluated the effect of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) on Th17-immune responses in an in vitro study using peripheral blood mononuclear cells (PBMCs) from healthy volunteers or KTRs. Next, we investigated mammalian target of rapamycin/STAT3 signaling as a mechanism by which 1,25(OH)2D3 exerted its effect on T cells using the Jurkat cell line. Third, we investigated Th17-cytokine levels or Th17 cell percentage in PBMCs according to the serum 25-hydroxyvitamin D (25(OH)D) level in 81 KTRs, and we performed a prospective study to assess whether 1,25(OH)2D3 (calcitriol) treatment decreased Th17 cytokine levels (IL-17, IL-22) in 42 KTRs. Results: In the in vitro study, we observed that the addition of 1,25(OH)2D3 to Tac significantly inhibited the appearance of IL-17-positive cells in culture. The expression of IL-17 and IL-22 messenger RNA in PBMCs was also decreased by the addition of 1,25(OH)2D3. In the Jurkat cell line, the mTOR/STAT3 pathway was further downregulated with the addition of 1,25(OH)2D3 to Tac. In the 81 KTRs, the 25(OH)D level was inversely correlated with the Th17 cytokine levels or the proportion of Th17 cell out of CD4+ T cells. Treatment with calcitriol for 6 months significantly decreased Th17 cytokine levels compared with the baseline values in another 42 KTRs. Conclusions: Treatment with 1,25(OH)2D3 may have immunologic benefits by effectively suppressing the Th17-related immune responses in KTRs on Tac-based immunosuppression.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Ge, Shili; Karasyov, Artur; Sinha, Aditi; Petrosyan, Anna; Lovato, Darly; Thomas, David L.; Vo, Ashley; Jordan, Stan C.; Toyoda, Mieko
    Cytomegalovirus Immunity After Alemtuzumab Induction in Desensitized Kidney Transplant Patients
    imageBackground: Desensitization with IVIG + rituximab combined with alemtuzumab induction gives HLA-sensitized patients an opportunity for successful kidney transplantation. However, it may be associated with a high risk for viral infections due to combined T cell and B cell depletion. Methods: Anti-cytomegalovirus (CMV) activity was assessed in 280 pretransplant and posttransplant blood samples from 33 desensitized patients who received alemtuzumab induction. CMV-specific CD8+ (CMV-Tc), CD4+ (CMV-Th) T cell activity, and natural killer (NK) cell number were measured by flow cytometry. Anti-CMV IgG was measured by enzyme-linked immunosorbent assay, and CMV DNA by polymerase chain reaction. Results: All 30 CMV sero (+) patients were (+) for CMV-Tc and/or Th predesensitization, while 3 sero (−) patients showed no CMV-T cell activity. CMV-Tc and/or Th became (−) in 50% to 70% of these sero (+) patients at 1 month post-alemtuzumab. However, 75% showed CMV-T cell (+) by 2 months and 95% did so by 3 months post-alemtuzumab. More than 50% of pretranslpant NK cell levels were detected post-alemtuzumab. Anti-CMV IgG levels did not decrease posttransplant in sero (+) patients. Four patients developed CMV viremia with clearance by 1.2 months, which correlated with an increase or appearance of CMV-T cells, even in the sero (−) patient. Conclusions: CMV-T cell activity, anti-CMV IgG, and NK cell-mediated antibody-dependent cell cytotoxicity were present in aleumtuzumab-treated CMV sero (+) patients. One sero (−) patient developed CMV-T cell responses post-CMV viremia. These results suggest that the IVIG + rituximab desensitization combined with alemtuzmab induction with triple immunosuppression maintenance does not result in prolonged suppression of anti-CMV immunity or increased risk for CMV infection.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Veenhof, Herman; Koster, Remco A.; Alffenaar, Jan-Willem C.; Berger, Stefan P.; Bakker, Stephan J.L.; Touw, Daan J.
    Clinical Validation of Simultaneous Analysis of Tacrolimus, Cyclosporine A, and Creatinine in Dried Blood Spots in Kidney Transplant Patients
    imageBackground: Monitoring of creatinine and immunosuppressive drug concentrations, such as tacrolimus (TaC) and cyclosporin A (CsA), is important in the outpatient follow-up of kidney transplant recipients. Monitoring by dried blood spot (DBS) provides patients the opportunity to sample a drop of blood from a fingerprick at home, which can be sent to the laboratory by mail. Methods: We performed a clinical validation in which we compared measurements from whole-blood samples obtained by venapuncture with measurements from DBS samples simultaneously obtained by fingerprick. After exclusion of 10 DBS for poor quality, and 2 for other reasons, 199, 104, and 58 samples from a total of 172 patients were available for validation of creatinine, TaC and CsA, respectively. Validation was performed by means of Passing & Bablok regression, and bias was assessed by Bland-Altman analysis. Results: For creatinine, we found y = 0.73x - 1.55 (95% confidence interval [95% CI] slope, 0.71-0.76), giving the conversion formula: (creatinine plasma concentration in μmol/L) = (creatinine concentration in DBS in μmol/L)/0.73, with a nonclinically relevant bias of −2.1 μmol/L (95% CI, −3.7 to −0.5 μmol/L). For TaC, we found y = 1.00x - 0.23 (95% CI slope, 0.91-1.08), with a nonclinically relevant bias of −0.28 μg/L (95% CI, −0.45 to −0.12 μg/L). For CsA, we found y = 0.99x - 1.86 (95% CI slope, 0.91-1.08) and no significant bias. Therefore, for neither TaC nor CsA, a conversion formula is required. Conclusions: DBS sampling for the simultaneous analysis of immunosuppressants and creatinine can replace conventional venous sampling in daily routine.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Jiménez-Romero, Luis Carlos; Caso Maestro, Oscar; Cambra Molero, Félix; Manrique Municio, Alejandro; Calvo Pulido, Jorge; Marcacuzco Quinto, Alberto; Justo Alonso, Iago
    Octogenarian Liver Grafts Reaching Centennial Age After Transplantation
    imageNo abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Simonetta, Federico; Pradier, Amandine; Masouridi-Levrat, Stavroula; van Delden, Christian; Giostra, Emiliano; Morard, Isabelle; Mueller, Nicolas; Muellhaupt, Beat; Valli, Piero V.; Semmo, Nasser; Seebach, Jörg; Chalandon, Yves; Kaiser, Laurent; Roosnek, Eddy; Swiss Transplant Cohort Study (STCS)
    Torque Teno Virus Load and Acute Rejection After Orthotopic Liver Transplantation
    imageNo abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Chen, Chuan-bao; Zhou, Jian; Wang, Xiao-ping; Han, Ming; Chen, Wen-fang; Yuan, Xiao-peng
    Successful Transplantation of 2 Discolored Kidneys Caused by Myoglobin Casts From a Donor With Rhabdomyolysis
    imageNo abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    De Carlis, Riccardo; Lauterio, Andrea; Ferla, Fabio; Di Sandro, Stefano; Sguinzi, Raffaella; De Carlis, Luciano
    Hypothermic Machine Perfusion of Liver Grafts Can Safely Extend Cold Ischemia for Up to 20 Hours in Cases of Necessity
    imageNo abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Descamps, Vincent; Brunet-Possenti, Florence
    Human Herpesvirus 6 Reactivation in DRESS With Acute Liver Failure: A Missing Key Factor
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Garrouste, Cyril; Rosset, Eugenio; Quainon, Fabienne; Aniort, Julien; Heng, Anne Elisabeth
    Alloimmunization After Cryopreserved Arterial Allografts in a Patient on a Kidney Transplantation Waiting List
    imageNo abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Aly, Mostafa G.; Opelz, Gerhard; Daniel, Volker
    Vitamin D and TH17 Lymphocytes
    imageNo abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    Chung, Byung Ha; Yang, Chul Woo
    The Authors’ Reply
    No abstract available


    Date de mise en ligne : Jeudi 01 janvier 1970
    The Effects of Valsartan on Renal Klotho Expression and Oxidative Stress in Alleviation of Cyclosporine Nephrotoxicity: Retraction
    No abstract available