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Complement kidney donor

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https://www.readbyqxmd.com/read/28587616/a-double-blind-randomised-controlled-investigation-into-the-efficacy-of-mirococept-apt070-for-preventing-ischaemia-reperfusion-injury-in-the-kidney-allograft-empirikal-study-protocol-for-a-randomised-controlled-trial
#1
Theodoros Kassimatis, Anass Qasem, Abdel Douiri, Elizabeth G Ryan, Irene Rebollo-Mesa, Laura L Nichols, Roseanna Greenlaw, Jonathon Olsburgh, Richard A Smith, Steven H Sacks, Martin Drage
BACKGROUND: Delayed graft function (DGF) is traditionally defined as the requirement for dialysis during the first week after transplantation. DGF is a common complication of renal transplantation, and it negatively affects short- and long-term graft outcomes. Ischaemia reperfusion injury (IRI) is a prime contributor to the development of DGF. It is well established that complement system activation plays a pivotal role in the pathogenesis of IRI. Mirococept is a highly effective complement inhibitor that can be administered ex vivo to the donor kidney just before transplantation...
June 6, 2017: Trials
https://www.readbyqxmd.com/read/28558950/complement-in-renal-transplantation-the-road-to-translation
#2
Neeltina M Jager, Felix Poppelaars, Mohamed R Daha, Marc A Seelen
Renal transplantation is the treatment of choice for patients with end-stage renal disease. The vital role of the complement system in renal transplantation is widely recognized. This review discusses the role of complement in the different phases of renal transplantation: in the donor, during preservation, in reperfusion and at the time of rejection. Here we examine the current literature to determine the importance of both local and systemic complement production and how complement activation contributes to the pathogenesis of renal transplant injury...
May 27, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28544308/use-of-a-new-end-stage-kidney-disease-risk-calculator-in-the-kidney-disease-improving-global-outcomes-guideline-to-evaluate-the-impact-of-different-living-kidney-donor-candidate-assessments
#3
Darren Lee, Momena Manzoor, Geoff Harley, John Whitlam, Natasha Cook, Suet-Wan Choy, Megan Sandiford, Charlotte Gibson, Lawrence P McMahon, Matthew A Roberts
AIM: The Kidney Disease Improving Global Outcomes (KDIGO) guideline recommends the incorporation of a new risk calculator that quantifies the end stage kidney disease (ESKD) risk based on a composite profile of risk factors in living kidney donor candidates (LKDCs). We compared the ESKD risk estimates in previously declined versus accepted LKDCs to evaluate the predictive capacity and potential impact of this tool. METHODS: Baseline 15-year and lifetime ESKD risk estimates without donation were calculated using the risk calculator for LKDCs assessed from two centres between 2007 and 2015...
May 20, 2017: Nephrology
https://www.readbyqxmd.com/read/28536887/ficolin-2-gene-rs7851696-polymorphism-is-associated-with-delayed-graft-function-and-acute-rejection-in-kidney-allograft-recipients
#4
Ewa Dabrowska-Zamojcin, Michal Czerewaty, Damian Malinowski, Maciej Tarnowski, Sylwia Słuczanowska-Głabowska, Leszek Domanski, Krzysztof Safranow, Andrzej Pawlik
Ficolin-2 is an activator of the complement system that acts via the lectin pathway. Complement activation plays a substantial role in the renal injury inherent to kidney transplantation. In this study, we examined the associations between ficolin-2 gene polymorphisms in exon 8 and kidney allograft function. This study comprised 270 Caucasian deceased-donor renal transplant recipients. The following parameters were recorded in each case: delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction...
May 23, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28447925/luminex-solid-phase-crossmatch-for-de-novo-donor-specific-antibodies-in-living-donor-related-transplants
#5
Sonia Mehrotra, Raj Kumar Sharma, Mahabaleshwar Mayya, Amit Gupta, Narayan Prasad, Anupma Kaul, Dharmendra Singh Bhadauria
OBJECTIVES: There are no reports of de novo donor-specific antibody monitoring by a low-cost solid-phase crossmatch assay using donor lysate after renal transplant. MATERIALS AND METHODS: We prospectively evaluated 121 complement-dependant cytotoxicity crossmatch-negative living-donor kidney transplant recipients for development of de novo donor-specific antibodies (class I and II HLA) by solid-phase crossmatch Luminex assay after transplant. RESULTS: Of 121 recipients in our study group, 26 (21...
April 27, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28446536/donor-specific-antibodies-in-kidney-transplant-recipients
#6
REVIEW
Rubin Zhang
Donor-specific antibodies have become an established biomarker predicting antibody-mediated rejection. Antibody-mediated rejection is the leading cause of graft loss after kidney transplant. There are several phenotypes of antibody-mediated rejection along post-transplant course that are determined by the timing and extent of humoral response and the various characteristics of donor-specific antibodies, such as antigen classes, specificity, antibody strength, IgG subclasses, and complement binding capacity...
April 26, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28428030/complement-inhibition-with-eculizumab-for-thrombotic-microangiopathy-rescues-a-living-donor-kidney-transplant-in-a-patient-with-antiphospholipid-antibody-syndrome
#7
Praveen Ramakrishnan Geethakumari, Patrick Mille, Rakesh Gulati, Srikanth Nagalla
Antiphospholipid antibody syndrome (APS) is an enigmatic heterogeneous disorder despite several revelations in its pathobiology. Renal transplantation in patients with APS has been notoriously difficult due to the high risk of development of thrombotic microangiopathy (TMA), which is often refractory to conventional treatment modalities such as aggressive anticoagulation and plasmapheresis. We describe a case of a 58-year-old male with secondary APS undergoing living unrelated renal transplantation for end-stage renal disease from lupus nephritis...
March 10, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28421681/early-clinical-xenotransplantation-experiences-an-interview-with-thomas-e-starzl-md-phd
#8
REVIEW
David K C Cooper
Dr Thomas E. Starzl, who died on March 4, 2017, was one of the great pioneers of organ transplantation. He was also a pioneer in the field of xenotransplantation. In 1964, he carried out baboon kidney transplants in six patients with terminal renal disease for whom no living or deceased donor became available; graft survival was for 19-60 days, the grafts being lost largely through continuous complement activation. Between 1966 and 1974, he carried out one ex vivo liver perfusion and three orthotopic liver transplants using chimpanzees as sources of organs; graft survival was for <14 days...
March 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28419995/hemolytic-uremic-syndrome-and-kidney-transplantation-a-case-series-and-review-of-the-literature
#9
Sabrina Milan Manani, Grazia Maria Virzì, Anna Giuliani, Anna Clementi, Alessandra Brocca, Daniela Dissegna, Francesca Martino, Emanuele Stefano Giovanni d'Amore, Claudio Ronco
BACKGROUND: Hemolytic uremic syndrome (HUS) can be triggered by Shiga toxin producing Escherichia coli (STEC) infection or it can be defined as atypical HUS (aHUS) if it is related to uncontrolled complement activation. aHUS is characterized by a high incidence of recurrence after kidney transplantation, and it can also occur de novo in transplant recipients. Eculizumab is used both to prevent and to treat aHUS following kidney transplantation. In this paper, we report our centre experience and we present 4 cases of HUS in patients who underwent kidney transplantation...
April 19, 2017: Nephron
https://www.readbyqxmd.com/read/28367453/de-novo-donor-specific-hla-antibodies-developing-early-or-late-after-transplant-are-associated-with-the-same-risk-of-graft-damage-and-loss-in-nonsensitized-kidney-recipients
#10
Michela Cioni, Arcangelo Nocera, Annalisa Innocente, Augusto Tagliamacco, Antonella Trivelli, Sabrina Basso, Giuseppe Quartuccio, Iris Fontana, Alberto Magnasco, Francesca Drago, Antonella Gurrado, Ilaria Guido, Francesca Compagno, Giacomo Garibotto, Catherine Klersy, Enrico Verrina, Gian Marco Ghiggeri, Massimo Cardillo, Patrizia Comoli, Fabrizio Ginevri
De novo posttransplant donor-specific HLA-antibody (dnDSA) detection is now recognized as a tool to identify patients at risk for antibody-mediated rejection (AMR) and graft loss. It is still unclear whether the time interval from transplant to DSA occurrence influences graft damage. Utilizing sera collected longitudinally, we evaluated 114 consecutive primary pediatric kidney recipients grafted between 2002 and 2013 for dnDSA occurrence by Luminex platform. dnDSAs occurred in 39 patients at a median time of 24...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28348361/the-impact-of-donor-specific-anti-human-leukocyte-antigen-hla-antibody-rebound-on-the-risk-of-antibody-mediated-rejection-in-sensitized-kidney-transplant-recipients
#11
Kyo Won Lee, Jae Berm Park, Chan Woo Cho, Nuri Lee, Heejin Yoo, Kyunga Kim, Hyojun Park, Eun Suk Kang, Wooseong Huh, Sungjoo Kim
BACKGROUND Donor-specific anti-HLA antibody (DSA) detected on Luminex-based single antigen assay (LSA) has become the subject of desensitization based upon the results of previous studies. We retrospectively investigated the impact of preoperative DSA on the incidence of antibody mediated rejection (AMR) in patients desensitized using a protocol based on rituximab and rabbit antithymocyte globulin (rATG). MATERIAL AND METHODS Nine patients (Group 1, 9/327, 2.8%) were complement dependent cytotoxicity crossmatch (CDC-XM) positive and underwent desensitization with rituximab (375 mg/m²), intravenous immunoglobulin (IVIG; 400 mg/kg), plasmapheresis, and rATG...
March 28, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28340811/tac-mmf-versus-csa-mmf-csa-aza-based-regimens-in-development-of-de-novo-complement-binding-anti-hla-antibodies-after-kidney-transplantation
#12
T Sahutoglu, S U Akgul, Y Caliskan, H Yazici, E Demir, E Kara, S Temurhan, F O Savran, A Turkmen
BACKGROUND: Immunosuppressive regimens with tacrolimus or cyclosporine A (CsA) were compared for graft-related outcomes in conjunction with complement-binding de novo donor-specific antibodies (DSAs). METHODS: Non-sensitized adult patients without rejection episodes within 3 months after transplantation were screened for the presence of de novo DSAs and C1q binding. Clinical and biopsy data were retrospectively obtained. RESULTS: The analysis included 118 patients (68 tacrolimus, 50 CsA), with mean age and follow-up of 36...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28330741/intermediate-steroid-withdrawal-after-renal-transplantation-and-anti-hla-antibodies-hla-abs-development
#13
Elena Monfá, David San Segundo, Juan Carlos Ruiz San Millán, Judith Sanabria, Zoila Albines, Emilio Rodrigo, Iñigo Romón, Esther Asensio, Manuel Arias, Marcos López-Hoyos
INTRODUCTION: Steroid withdrawal in renal transplantation is desirable to avoid their adverse effects. However, by decreasing the immunosuppression, could lead to an increased risk for the development of HLA-Abs. OBJECTIVE: Evaluate the relationship between steroid withdrawal and development of HLA-Abs in renal transplantation. METHODS: We analyzed sera by Luminex from 182 kidney transplants performed from 1998 to 2011, before and two years after transplantation...
March 19, 2017: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/28322169/potential-therapeutic-strategies-of-regenerative-medicine-for-renal-failure
#14
Monica Maribel Mata-Miranda, Raul Jacobo Delgado-Macuil, Marlon Rojas-Lopez, Ricardo Martinez-Flores, Gustavo Jesus Vazquez-Zapien
Kidney diseases are a public health problem worldwide; the mortality rate is between 50 and 80%. Available therapies include replacement function by dialysis or transplant, associated with a high morbidity and mortality; kidney transplantation is limited by the shortage of donor organs, immune rejection and lifelong treatment with immunosuppressive. Likewise, none of these treatments compensates all kidney functions. There is a great concern in developing more effective therapies with the ability to replace the wide range of renal functions, so that, new researches on developing therapeutic strategies have focused on regenerative medicine, science that includes artificial creation of tissues and organs, in order to repair or replace a tissue or organ function...
March 17, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28303661/immunological-and-physiological-observations-in-baboons-with-life-supporting-genetically-engineered-pig-kidney-grafts
#15
Hayato Iwase, Hidetaka Hara, Mohamed Ezzelarab, Tao Li, Zhongqiang Zhang, Bingsi Gao, Hong Liu, Cassandra Long, Yi Wang, Amy Cassano, Edwin Klein, Carol Phelps, David Ayares, Abhinav Humar, Martin Wijkstrom, David K C Cooper
BACKGROUND: Genetically engineered pigs could provide a source of kidneys for clinical transplantation. The two longest kidney graft survivals reported to date have been 136 and 310 days, but graft survival >30 days has been unusual until recently. METHODS: Donor pigs (n=4) were on an α1,3-galactosyltransferase gene-knockout (GTKO)/human complement regulatory protein (CD46) background (GTKO/CD46). In addition, the pigs were transgenic for at least one human coagulation regulatory protein...
March 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28176480/de-novo-thrombotic-microangiopathy-following-simultaneous-pancreas-and-kidney-transplantation-managed-with-eculizumab
#16
REVIEW
Lani Shochet, John Kanellis, Ian Simpson, Joseph Ta, William Mulley
Thrombotic microangiopathy (TMA) is a well-recognised complication following transplantation, often due to an underlying genetic predisposition, medications or rejection. The use of eculizumab in these settings has been previously described, but its role still remains to be clarified. A 45-year-old man, with a history of type 1 diabetes mellitus and subsequent end-stage kidney failure, presented for a simultaneous pancreas-kidney transplant. Immunologically, he was well matched with the donor, and he received standard induction immunosuppression including tacrolimus...
February 2017: Nephrology
https://www.readbyqxmd.com/read/28176477/absence-of-thrombocytopaenia-and-or-microangiopathic-haemolytic-anaemia-does-not-reliably-exclude-recurrence-of-atypical-haemolytic-uraemic-syndrome-after-kidney-transplantation
#17
REVIEW
Anoushka R Krishnan, Brian Siva, Aron Chakera, Germaine Wong, Daniel Wong, Wai H Lim
A 54-year-old man was diagnosed with atypical haemolytic uraemic syndrome (aHUS) with confirmed complement H mutation in 2012, requiring ongoing dialysis. He was commenced on eculizumab in 2014 once the pharmaceutical board approved this drug. After 4 months, he received a live unrelated donor renal transplant from his wife and continued eculizumab post-transplant. Three months later, there was a rise in his creatinine with no laboratory features of haemolysis and a kidney biopsy confirmed rejection, which was treated with increased immunosuppression...
February 2017: Nephrology
https://www.readbyqxmd.com/read/28133619/from-humoral-theory-to-performant-risk-stratification-in-kidney-transplantation
#18
REVIEW
C Lefaucheur, D Viglietti, M Mangiola, A Loupy, A Zeevi
The purpose of the present review is to describe how we improve the model for risk stratification of transplant outcomes in kidney transplantation by incorporating the novel insights of donor-specific anti-HLA antibody (DSA) characteristics. The detection of anti-HLA DSA is widely used for the assessment of pre- and posttransplant risks of rejection and allograft loss; however, not all anti-HLA DSA carry the same risk for transplant outcomes. These antibodies have been shown to cause a wide spectrum of effects on allografts, ranging from the absence of injury to indolent or full-blown acute antibody-mediated rejection...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28104125/efficacy-of-eculizumab-therapy-for-atypical-hemolytic-uremic-syndrome-recurrence-and-antibody-mediated-rejection-progress-after-renal-transplantation-with-preformed-donor-specific-antibodies-case-report
#19
T Yamamoto, Y Watarai, K Futamura, M Okada, M Tsujita, T Hiramitsu, N Goto, S Narumi, A Takeda, T Kobayashi
Atypical hemolytic uremic syndrome (aHUS) develops as the result of unregulated complement progression and precipitates de novo thrombotic microangiopathy. Plasma therapy is used to control the progression of the complement cascade, but that therapy is not effective in all patients and is accompanied by risk of infection and/or allergy. Eculizumab has been reported as an efficient therapy for aHUS. We report the case of a 35-year old woman who underwent effective eculizumab therapy for aHUS recurrence and antibody-mediated rejection (AMR) progress after renal transplantation with preformed donor-specific antibodies (DSA)...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28097805/complement-polymorphisms-in-kidney-transplantation-critical-in-graft-rejection
#20
REVIEW
L A Michielsen, A D van Zuilen, I S Muskens, M C Verhaar, H G Otten
The complement system, as part of the innate immune system, plays an important role in renal transplantation. Complement is involved in the protection against foreign organisms and clearance of apoptotic cells but can also cause injury to the renal allograft, for instance, via antibody binding or in ischemia-reperfusion injury. Numerous polymorphisms in complement factors have been identified thus far; some of them result in different functionalities or alter complement levels. In this review, we provide an overview of the literature on the role of complement polymorphisms in renal transplantation...
January 17, 2017: American Journal of Transplantation
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