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Complement kidney donor

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https://www.readbyqxmd.com/read/29135832/prognostic-value-of-the-persistence-of-c1q-binding-anti-hla-antibodies-in-acute-antibody-mediated-rejection-in-kidney-transplantation
#1
Elodie Bailly, Dany Anglicheau, Gilles Blancho, Philippe Gatault, Vincent Vuiblet, Valérie Chatelet, Emmanuel Morelon, Paolo Malvezzi, Anne Parissiadis, Jérôme Tourret, Gwendaline Guidicelli, Johnny Sayegh, Christiane Mousson, Philippe Grimbert, Isabelle Top, Moglie Le Quintrec, Raj Purgus, Pierre François Westeel, Barbara Proust, Valérie Chabot, Yvon Lebranchu, Frédéric Dehaut, Matthias Büchler
BACKGROUND: The differential pathogenicity of anti-HLA donor-specific antibodies (DSAs) is not fully understood. The presence of complement-binding DSAs help better defining the prognosis of acute antibody-mediated rejection (ABMR). The evolution of these antibodies after the treatment of ABMR is unknown. METHODS: We included patients from the French multicenter RITUX ERAH study diagnosed with acute antibody-mediated rejection (ABMR) within the first year of renal transplantation, with circulating anti-HLA DSAs and treated randomly by rituximab or placebo (and intravenous immunoglobulins, plasma exchange)...
November 13, 2017: Transplantation
https://www.readbyqxmd.com/read/29130538/-what-if-this-is-my-chance-to-save-my-life-a-semi-structured-interview-study-on-the-motives-and-experiences-of-esrd-patients-who-engaged-in-public-solicitation-of-a-living-kidney-donor
#2
Mathilde C Pronk, Dorthe Slaats, Willij C Zuidema, Medard T Hilhorst, Frank J M F Dor, Michiel Betjes, Willem Weimar, Jacqueline van de Wetering, Emma K Massey
The increase of patients using public solicitation (PS) to find a living kidney donor has generated a debate about the ethical complexities of PS. To investigate why patients engaged in PS and what they experienced during PS we conducted semi-structured interviews with 20 Dutch end-stage renal disease patients who had publicly solicited a living donor. Transcipts were thematically analyzed. We identified ten themes on patients' considerations preceding PS: cautiousness in discussing living donation within social network; reluctance to accept a kidney from loved ones; rejection/withdrawal of related donor candidates; moral objections to black market organs/paid donation; the ease of social media; encouraged by others; ends justyfying the means; despair and urge to take action; public disclosure of vulnerability; fear of being (perceived to be) selfish...
November 12, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/29042454/complement-activating-anti-hla-antibodies-in-kidney-transplantation-allograft-gene-expression-profiling-and-response-to-treatment
#3
Carmen Lefaucheur, Denis Viglietti, Luis G Hidalgo, Lloyd E Ratner, Serena M Bagnasco, Ibrahim Batal, Olivier Aubert, Babak J Orandi, Federico Oppenheimer, Oriol Bestard, Paolo Rigotti, Anna V Reisaeter, Nassim Kamar, Yvon Lebranchu, Jean-Paul Duong Van Huyen, Patrick Bruneval, Denis Glotz, Christophe Legendre, Jean-Philippe Empana, Xavier Jouven, Dorry L Segev, Robert A Montgomery, Adriana Zeevi, Philip F Halloran, Alexandre Loupy
Complement-activating anti-HLA donor-specific antibodies (DSAs) are associated with impaired kidney transplant outcome; however, whether these antibodies induce a specific rejection phenotype and influence response to therapy remains undetermined. We prospectively screened 931 kidney recipients for complement-activating DSAs and used histopathology, immunostaining, and allograft gene expression to assess rejection phenotypes. Effector cells were evaluated using in vitro human cell cultures. Additionally, we assessed the effect of complement inhibition on kidney allograft rejection phenotype and the clinical response to complement inhibition in 116 independent kidney recipients with DSAs at transplant receiving rejection prophylaxis with eculizumab or standard of care (plasma exchange and intravenous Ig) at ten international centers...
October 17, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28980446/anti-c1s-monoclonal-antibody-bivv009-in-late-antibody-mediated-kidney-allograft-rejection-results-from-a-first-in-patient-phase-1-trial
#4
F Eskandary, B Jilma, J Mühlbacher, M Wahrmann, H Regele, N Kozakowski, C Firbas, S Panicker, G C Parry, J C Gilbert, P F Halloran, G A Böhmig
The classical pathway (CP) of complement may contribute to the pathogenesis of antibody-mediated rejection (ABMR). Selective CP blockade may be a promising strategy to counteract rejection. The objective of this first-in-patient phase 1b trial was to evaluate the safety/tolerability and CP-blocking potential of four weekly doses (60 mg/kg) of the anti-C1s antibody BIVV009 in complement-mediated disorders. Here we describe the results in a cohort of 10 stable kidney transplant recipients (median of 4.3 years post-transplantation) with late active ABMR and features of CP activation, such as capillary C4d or complement-fixing donor-specific antibodies (DSA)...
October 5, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28970687/detection-of-t-and-b-cells-specific-complement-fixing-alloantibodies-using-flow-cytometry-a-diagnostic-approach-for-a-resource-limited-laboratory
#5
Dharmendra Jain, Pranav Dorwal, Amit Pande, Neetu Tyagi, Simmi Mehra, Vimarsh Raina
BACKGROUND AND OBJECTIVES: Various methods have been reported for the detection of antibodies in recipient sera, which can be human leukocyte antigens (HLAs) or non-HLA specific, complement- or noncomplement fixing, as well as donor T (HLA-Class-I) and/or B cell (HLA-Class-I and II) specific. These alloantibodies play a pivotal role in antibody-mediated renal transplantation rejection. Deposition of C4d in peritubular capillaries of a kidney biopsy is a marker of antibody-mediated rejection...
July 2017: Asian Journal of Transfusion Science
https://www.readbyqxmd.com/read/28953652/successful-kidney-transplantation-across-a-positive-complement-dependent-cytotoxicity-crossmatch-by-using-c1q-assay-directed-bortezomib-assisted-desensitization-a-case-report
#6
Juhan Lee, Borae G Park, Hyang Sook Jeong, Youn Hee Park, Sinyoung Kim, Beom Seok Kim, Hye Jin Kim, Kyu Ha Huh, Hyeon Joo Jeong, Yu Seun Kim
RATIONALE: Human leukocyte antigen (HLA) is the major immunologic barrier in kidney transplantation (KT). Various desensitization protocols to overcome the HLA barrier have increased the opportunity for transplantation in sensitized patients. In addition, technological advances in solid-phase assays have permitted more comprehensive assessment of donor-specific antibodies. Although various desensitization therapies and immunologic techniques have been developed, the final transplantation decision is still based on the classic complement-dependent cytotoxicity (CDC) crossmatch (XM) technique...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28882367/defining-the-phenotype-of-antibody-mediated-rejection-in-kidney-transplantation-advances-in-diagnosis-of-antibody-injury
#7
REVIEW
Neetika Garg, Milagros D Samaniego, Dana Clark, Arjang Djamali
The diagnostic criteria for antibody-mediated rejection (ABMR) are constantly evolving in light of the evidence. Inclusion of C4d-negative ABMR has been one of the major advances in the Banff Classification in recent years. Currently Banff 2015 classification requires evidence of donor specific antibodies (DSA), interaction between DSA and the endothelium, and acute tissue injury (in the form of microvasculature injury (MVI); acute thrombotic microangiopathy; or acute tubular injury in the absence of other apparent cause)...
August 15, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28865128/mechanisms-underlying-human-genetic-diversity-consequence-for-anti-graft-antibody-responses
#8
REVIEW
Roman Reindl-Schwaighofer, Andreas Heinzel, Lorenzo Signorini, Olivier Thaunat, Rainer Oberbauer
This review focuses on the emerging concept of genome-wide genetic variation as basis of an alloimmune response. Chronic antibody mediated rejection is the major cause of long-term graft loss and growing evidence supports the clinical relevance of HLA but also non-HLA related alloimmune responses. Several polymorphic gene products have been identified as minor histocompatibility antigens. The formation of donor specific alloantibodies is driven by indirect allorecognition of donor derived peptides representing a form of conventional T-cell response...
September 2, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28852487/rare-genetic-variants-in-shiga-toxin-associated-haemolytic-uraemic-syndrome-genetic-analysis-prior-to-transplantation-is-essential
#9
Frances Dowen, Katrina Wood, Alison L Brown, Jennifer Palfrey, David Kavanagh, Vicky Brocklebank
We present a case of haemolytic uraemic syndrome (HUS) in a 16-year-old female with serological evidence of acute Escherichia coli O157:H7 infection. She progressed to established renal failure and received a deceased donor kidney transplant. Shiga toxin-associated HUS (STEC-HUS) does not recur following renal transplantation, but unexpectedly this patient did experience rapid and severe HUS recurrence. She responded to treatment with the terminal complement inhibitor eculizumab and subsequent genetic analysis revealed a rare variant in a complement gene...
August 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28838443/first-treatment-of-relapsing-rapidly-progressive-iga-nephropathy-with-eculizumab-after-living-kidney-donation-a-case-report
#10
A L Herzog, C Wanner, K Amann, K Lopau
BACKGROUND: IgA nephropathy (IGAN) rarely can present as a crescent and progressive form leading to end-stage renal disease (ESRD) in a short period of time. Recurrence of IGAN after kidney transplantation is frequent, and complement components such as C3, C4d, and C5 seem to be involved. We present a case of a young male patient with ESRD caused by rapidly progressive IGAN and who demonstrated rapid recurrence of crescentic IGAN after kidney donation. CASE REPORT: In September 2014, a 28-year-old male patient was hospitalized due to IGAN with 60% of crescents...
September 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28821363/living-donor-kidney-transplantation-in-atypical-hemolytic-uremic-syndrome-a-case-series
#11
Caroline Duineveld, Jacobien C Verhave, Stefan P Berger, Nicole C A J van de Kar, Jack F M Wetzels
BACKGROUND: The development of complement inhibitors has greatly improved the outcome of patients with atypical hemolytic uremic syndrome (aHUS), making kidney transplantation a more feasible option. Although prophylactic eculizumab therapy may prevent recurrent disease after transplantation, its necessity for all transplant recipients is debated. STUDY DESIGN: A case series. SETTING & PARTICIPANTS: Patients with aHUS who underwent living donor kidney transplantation after 2011 at 2 university centers, prospectively followed up with a protocol of eculizumab therapy limited to only recipients with documented posttransplantation recurrent thrombotic microangiopathy...
August 16, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28767349/igg-endopeptidase-in-highly-sensitized-patients-undergoing-transplantation
#12
MULTICENTER STUDY
Stanley C Jordan, Tomas Lorant, Jua Choi, Christian Kjellman, Lena Winstedt, Mats Bengtsson, Xiaohai Zhang, Torsten Eich, Mieko Toyoda, Britt-Marie Eriksson, Shili Ge, Alice Peng, Sofia Järnum, Kathryn J Wood, Torbjorn Lundgren, Lars Wennberg, Lars Bäckman, Erik Larsson, Rafael Villicana, Joe Kahwaji, Sabrina Louie, Alexis Kang, Mark Haas, Cynthia Nast, Ashley Vo, Gunnar Tufveson
BACKGROUND: Donor-specific antibodies create an immunologic barrier to transplantation. Current therapies to modify donor-specific antibodies are limited and ineffective in the most highly HLA-sensitized patients. The IgG-degrading enzyme derived from Streptococcus pyogenes (IdeS), an endopeptidase, cleaves human IgG into F(ab')2 and Fc fragments inhibiting complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, which suggests that IdeS might be useful for desensitization...
August 3, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28734583/kidney-transplantation-from-hla-incompatible-live-donors-efficiency-and-outcome-of-32-patients-after-desensitisation
#13
Constantino Fernández, María Calvo, Natacha Leite, Andrés López, Tamara Ferreiro, Roi Ribera, Rocío Seijo, Ángel Alonso
Desensitisation is a procedure undergone by the recipient of a kidney transplant from a donor who is cross-match positive. The aim of this study was to present the outcomes from our hospital of kidney transplant recipients from HLA-incompatible live donors after desensitisation. We studied 32 patients aged 46±14 years with a mean fluorescence intensity (MFI) versus class I HLA of 7979±4089 and 6825±4182 MFI versus class II and relative intensity scale (RIS) of 8.9±7.6. The complement-dependent cytotoxicity (CDC) cross-matching test was positive in 18 patients, flow cytometry was positive in 7 patients and donor-specific antibodies (DEA) were detected in 7...
July 19, 2017: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/28731906/c1-inhibitor-treatment-decreases-renal-injury-in-an-established-brain-dead-rat-model
#14
Felix Poppelaars, Neeltina M Jager, Juha Kotimaa, Henri G D Leuvenink, Mohamed R Daha, Cees van Kooten, Marc A Seelen, Jeffrey Damman
BACKGROUND: Kidneys derived from brain-dead (BD) donors have lower graft survival rates compared to kidneys from living donors. Complement activation plays an important role in brain death. The aim of our study was therefore to investigate the effect of C1-inhibitor (C1-INH) on BD-induced renal injury. METHODS: Brain death was induced in rats by inflating a subdurally placed balloon catheter. Thirty minutes after BD, rats were treated with saline, low-dose or high-dose C1-INH...
July 21, 2017: Transplantation
https://www.readbyqxmd.com/read/28708813/application-and-interpretation-of-histocompatibility-data-in-liver-transplantation
#15
Russell N Wesson, Eric W Etchill, Jacqueline Garonzik-Wang
PURPOSE OF REVIEW: There has been a resurgence of interest in histocompatibility as it applies to liver transplantation. The association of persistent and de-novo donor specific antibody (DSA) and outcomes after liver transplantation continues to be investigated. RECENT FINDINGS: Consensus continues to evolve regarding the existence of acute and chronic antibody-mediated rejection (AMR) and pathogenicity of DSA and associated pathologic findings after liver transplantation...
July 13, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28682798/accommodation-and-related-conditions-in-vascularized-composite-allografts
#16
Jeffrey L Platt, Christina L Kaufman, Mayara Garcia de Mattos Barbosa, Marilia Cascalho
PURPOSE OF REVIEW: The outcome of vascularized composite allografts (VCA) often appear unrelated to the presence of donor-specific antibodies (DSA) in blood of the recipient or deposition of complement in the graft. The attenuation of injury and the absence of rejection in other types of grafts despite manifest donor-specific immunity have been explained by accommodation (acquired resistance to immune-mediated injury), adaptation (loss of graft antigen) and/or enhancement (antibody-mediated antigen blockade)...
October 2017: Current Opinion in Organ Transplantation
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
#17
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
#18
REVIEW
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...
September 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
#19
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
#20
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
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