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Antibody mediated kidney rejection

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By P O Pediatrics, Nephrology
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)
Paolo Malvezzi, Thomas Jouve, Johan Noble, Lionel Rostaing
The number of kidney transplant candidates is increasing sharply. Among them, at least 20% are HLA sensitized. For these patients, in the setting of both living- and deceased-donor kidney transplant, we may face donor-specific alloantibodies at pretransplant. In such cases, the microlymphocytotoxicity crossmatch may or may not be positive. Kidney transplant with donor-specific antibodies at pretransplant is known as HLA-incompatible transplant. At present, we can use many methods to ensure that the kidney transplant is successful, provided that the recipient is desensitized before or after transplant...
August 2018: Experimental and Clinical Transplantation
Tomas Lorant, Mats Bengtsson, Torsten Eich, Britt-Marie Eriksson, Lena Winstedt, Sofia Järnum, Yvonne Stenberg, Anna-Karin Robertson, Kristina Mosén, Lars Björck, Lars Bäckman, Erik Larsson, Kathryn Wood, Gunnar Tufveson, Christian Kjellman
Safety, immunogenicity, pharmacokinetics, and efficacy of the IgG-degrading enzyme of Streptococcus pyogenes (IdeS [imlifidase]) were assessed in a single-center, open-label ascending-dose study in highly sensitized patients with chronic kidney disease. Eight patients with cytotoxic PRAs (median cytotoxic PRAs of 64%) at enrollment received 1 or 2 intravenous infusions of IdeS on consecutive days (0.12 mg/kg body weight ×2 [n = 3]; 0.25 mg/kg ×1 [n = 3], or 0.25 mg/kg ×2 [n = 2]). IgG degradation was observed in all subjects after IdeS treatment, with <1% plasma IgG remaining within 48 hours and remaining low up to 7 days...
November 2018: American Journal of Transplantation
R A Montgomery, A Loupy, D L Segev
Despite the success of desensitization protocols, antibody-mediated rejection (AMR) remains a significant contributor to renal allograft failure in patients with donor-specific antibodies. Plasmapheresis and high-dose intravenous immunoglobulin have proved to be effective treatments to prevent and treat AMR, but irreversible injury in the form of transplant glomerulopathy can commonly manifest months to years later. There is an unmet need to improve the outcomes for patients at risk for AMR. Updated Banff criteria now take into account the increasing understanding of the complex and heterogeneous nature of AMR phenotypes, including the timing of rejection, subclinical and chronic AMR, C4d-negative AMR, and antibody-mediated vascular rejection...
January 2018: American Journal of Transplantation
P F Halloran, M Merino Lopez, A Barreto Pereira
The key lesions in antibody-mediated kidney transplant rejection (ABMR) are microcirculation inflammation (peritubular capillaritis and/or glomerulitis lesions, abbreviated "pg") and glomerular double contours (cg lesions). We used these features to explore subphenotypes in 164 indication biopsies with ABMR-related diagnoses: 137 ABMR (109 pure and 28 mixed with T cell-mediated rejection [TCMR]) and 27 transplant glomerulopathy (TG), identified from prospective multicenter studies. The lesions indicated three ABMR subphenotypes: pgABMR, cgABMR, and pgcgABMR...
March 2016: American Journal of Transplantation
K C Gurudev, Sonika Puri, Mahesha Vankalakunti
No abstract text is available yet for this article.
December 2015: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
Juha P Peräsaari, Lauri E Kyllönen, Kaija T Salmela, Jussi M Merenmies
BACKGROUND: Sensitive screening methods have revealed that many patients have donor-specific human leucocyte antigen antibodies (DSAs) prior to transplantation, regardless of negative crossmatch results. The clinical significance of pre-transplant (pre-Tx) DSAs for early graft function has remained unclear. Our aim was to examine the association of DSAs with delayed graft function (DGF). METHODS: Pre-Tx sera of 771 patients who received kidney transplants in our single-centre study were retrospectively screened...
April 2016: Nephrology, Dialysis, Transplantation
Juhan Lee, Beom Seok Kim, Yongjung Park, Jae Geun Lee, Beom Jin Lim, Hyeon Joo Jeong, Yu Seun Kim, Kyu Ha Huh
PURPOSE: Recently, bortezomib has been used to treat antibody-mediated rejection (AMR) refractory to conventional treatment such as plasmapheresis, intravenous immunoglobulin, and rituximab. The authors aimed to describe their experiences when bortezomib was used to treat refractory AMR. MATERIALS AND METHODS: Eleven refractory AMR episodes treated with bortezomib were included in this study. The patients received one or two cycles of bortezomib (1.3 mg/m²) on days 1, 4, 8, and 11...
November 2015: Yonsei Medical Journal
Madelon van Agteren, Willem Weimar, Annelies E de Weerd, Peter A W Te Boekhorst, Jan N M Ijzermans, Jaqueline van de Wetering, Michiel G H Betjes
This study describes the single center experience and long-term results of ABOi kidney transplantation using a pretransplantation protocol involving immunoadsorption combined with rituximab, intravenous immunoglobulins, and triple immune suppression. Fifty patients received an ABOi kidney transplant in the period from 2006 to 2012 with a follow-up of at least one year. Eleven antibody mediated rejections were noted of which 5 were mixed antibody and cellular mediated rejections. Nine cellular mediated rejections were recorded...
2014: Journal of Transplantation
Hugo Kaneku
1. There is still a need to better differentiate clinically relevant from irrelevant DSA in all organs. Modified bead assay testing for different immunoglobulin (Ig) G characteristics (Clq-fixing DSA, C4d-fixing DSA, IgG subclasses, or IgM) often improve the predictive value for rejection and failure compared to standard IgG DSA. A new approach looking for intragraft DSA instead of serum DSA represents a very interesting attempt. The relevance of DSA may not solely be determined by antibody characteristics, but may be in the capacity of an antibody to bind specific antigens on the allograft...
2013: Clinical Transplants
Irina B Torres, Maite Salcedo, Francesc Moreso, Joana Sellarés, Eva Castellá, M Antonieta Azancot, Manel Perelló, Carme Cantarell, Daniel Serón
INTRODUCTION: Transplant glomerulopathy (TG) is the characteristic lesion of chronic antibody-mediated rejection (AMR). However, in some patients presents with no circulating HLA antibodies or C4d positivity. AIM: Patients with TG accomplishing criteria for chronic AMR were compared to patients with isolated TG. PATIENTS AND METHODS: We reviewed late (>6 months) graft biopsies performed between 2007 and 2010 (n = 75). Biopsies with C4d-negative TG and no circulating donor-specific antibody were called isolated TG (n = 12), and chronic AMR was defined according to Banff consensus (n = 17)...
October 2014: Clinical Transplantation
Antoine Sicard, Stéphanie Ducreux, Maud Rabeyrin, Lionel Couzi, Brigitte McGregor, Lionel Badet, Jean Yves Scoazec, Thomas Bachelet, Sébastien Lepreux, Jonathan Visentin, Pierre Merville, Véronique Fremeaux-Bacchi, Emmanuel Morelon, Jean-Luc Taupin, Valérie Dubois, Olivier Thaunat
Antibody-mediated rejection (AMR) is a major cause of kidney graft loss, yet assessment of individual risk at diagnosis is impeded by the lack of a reliable prognosis assay. Here, we tested whether the capacity of anti-HLA antibodies to bind complement components allows accurate risk stratification at the time of AMR diagnosis. Among 938 kidney transplant recipients for whom a graft biopsy was performed between 2004 and 2012 at the Lyon University Hospitals, 69 fulfilled the diagnosis criteria for AMR and were enrolled...
February 2015: Journal of the American Society of Nephrology: JASN
Clément Gosset, Carmen Lefaucheur, Denis Glotz
PURPOSE OF REVIEW: In the present review, we aim to describe the state of knowledge concerning antibody-mediated rejection (ABMR) spectrum and diagnosis criteria before analyzing the present and future promising leads regarding ABMR prognosis markers and treatment. RECENT FINDINGS: Recent studies regarding complement-binding donor-specific antibodies and the molecular approach highlighted the unmet need for stratification tools for prognosis and treatment inside ABMR disease...
November 2014: Current Opinion in Nephrology and Hypertension
Augusto Tagliamacco, Michela Cioni, Patrizia Comoli, Miriam Ramondetta, Caterina Brambilla, Antonella Trivelli, Alberto Magnasco, Roberta Biticchi, Iris Fontana, Pietro Dulbecco, Domenico Palombo, Catherine Klersy, Gian Marco Ghiggeri, Fabrizio Ginevri, Massimo Cardillo, Arcangelo Nocera
Data on the different HLA-antibody (Ab) categories in pediatric kidney recipients developing de novo donor-specific Abs (DSA) after transplantation are scarce. We retrospectively evaluated 82 consecutive nonsensitized pediatric recipients of a first kidney graft for de novo HLA Ab occurrence and antigen specificity. At a median follow-up of 6 years, 29% of patients developed de novo DSA, while 45% had de novo non-DSA. DSA appeared at 25-month median time post-transplant and were mostly directed toward HLA-DQ antigens...
July 2014: Transplant International: Official Journal of the European Society for Organ Transplantation
S Yamanaga, Y Watarai, A Takeda, T Yamamoto, T Hiramitsu, M Tsujita, N Goto, K Uchida, A Katayama, K Morozumi, T Kobayashi
A 61-year-old Japanese woman, who had undergone hemodialysis because of chronic glomerulonephritis, received a living renal transplant from her ABO blood type-compatible spouse. HLA typing of A, B and DRB showed 3/6 mismatches. Complement-dependent cytotoxicity crossmatches, HLA antibody screening with the use of flow panel reactive antibody (PRA), and flow cytometry crossmatches (FCXM) were all negative. Tacrolimus, mycophenolate mofetil, methylprednisolone (MP), and basiliximab induction were used as the standard immunosuppressive therapy...
2014: Transplantation Proceedings
Laure-Emmanuelle Croze, Rachel Tetaz, Matthieu Roustit, Paolo Malvezzi, Bénédicte Janbon, Thomas Jouve, Nicole Pinel, Dominique Masson, Jean-Louis Quesada, François Bayle, Philippe Zaoui
In kidney transplantation, conversion to mammalian target of rapamycin (mTOR) inhibitors may avoid calcineurin inhibitor (CNI) nephrotoxicity, but its impact on post-transplant allo-immunization remains largely unexplored. This retrospective cohort study analyzed the emergence of donor-specific antibodies (DSA) in kidney transplant recipients relative to their immunosuppressive therapy. Among 270 recipients without pretransplant immunization who were screened regularly for de novo DSA, 56 were converted to mTOR inhibitors after CNI withdrawal...
August 2014: Transplant International: Official Journal of the European Society for Organ Transplantation
Alexandre Loupy, Carmen Lefaucheur, Dewi Vernerey, Jessica Chang, Luis G Hidalgo, Thibaut Beuscart, Jerome Verine, Olivier Aubert, Sébastien Dubleumortier, Jean-Paul Duong van Huyen, Xavier Jouven, Denis Glotz, Christophe Legendre, Philip F Halloran
Antibody-mediated rejection (ABMR) is the leading cause of kidney allograft loss. We investigated whether the addition of gene expression measurements to conventional methods could serve as a molecular microscope to identify kidneys with ABMR that are at high risk for failure. We studied 939 consecutive kidney recipients at Necker Hospital (2004-2010; principal cohort) and 321 kidney recipients at Saint Louis Hospital (2006-2010; validation cohort) and assessed patients with ABMR in the first 1 year post-transplant...
October 2014: Journal of the American Society of Nephrology: JASN
William Hanf, Claudine S Bonder, P Toby H Coates
Transplant glomerulopathy (TG) is a major cause of chronic graft dysfunction without effective therapy. Although the histological definition of TG is well characterized, the pathophysiological pathways leading to TG development are still poorly understood. Electron microscopy suggests an earlier appearance of TG and suggests that endothelial cell injury is the first sign of the disease. The pathogenic role of human leukocyte antigen (HLA) antibodies in endothelial cells has been described in acute vascular and humoral rejection...
2014: Journal of Immunology Research
Gun Hee An, Jintak Yun, Yu Ah Hong, Marina Khvan, Byung Ha Chung, Bum Soon Choi, Cheol Whee Park, Yeong Jin Choi, Yong-Soo Kim, Chul Woo Yang
The treatment for chronic active antibody-mediated rejection (CAMR) remains controversial. We investigated the efficacy of rituximab (RTX) and intravenous immunoglobulin (IVIg) for CAMR. Eighteen patients with CAMR were treated with RTX (375 mg/m(2)) and IVIg (0.4 g/kg) for 4 days. The efficacy of RTX/IVIg combination therapy (RIT) was assessed by decline in estimated glomerular filtration rate per month (ΔeGFR) before and after RIT. Patients were divided into responder and nonresponder groups based on decrease and no decrease in ΔeGFR, respectively, and their clinical and histological characteristics were compared...
2014: Journal of Immunology Research
Miae Kim, Spencer T Martin, Keri R Townsend, Steven Gabardi
Antibody-mediated rejection (AMR), also known as B-cell-mediated or humoral rejection, is a significant complication after kidney transplantation that carries a poor prognosis. Although fewer than 10% of kidney transplant patients experience AMR, as many as 30% of these patients experience graft loss as a consequence. Although AMR is mediated by antibodies against an allograft and results in histologic changes in allograft vasculature that differ from cellular rejection, it has not been recognized as a separate disease process until recently...
July 2014: Pharmacotherapy
2014-05-22 15:08:08
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