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Humoral rejection in renal transplantation

Luca Dello Strologo, Luisa Murer, Isabella Guzzo, Federica Morolli, Annalisa M V Pipicelli, Elisa Benetti, Germana Longo, Sara Testa, Andrea Ricci, Fabrizio Ginevri, Luciana Ghio, Massimo Cardillo, Antonina Piazza, Alessandro Nanni Costa
BACKGROUND: High levels of preformed anti-HLA antibodies dramatically diminish renal transplant outcomes. Most desensitization programmes guarantee good intermediate outcomes but quite disappointing long-term prognosis. The search for a fully compatible kidney increases time on the waiting list. METHODS: In February 2011, a nationwide hyperimmune programme (NHP) was begun in Italy: all available kidneys are primarily proposed to highly sensitized patients with a panel reactive antibody above 80%...
October 14, 2016: Nephrology, Dialysis, Transplantation
Carrie Schinstock, Mark D Stegall
Acute antibody mediated rejection (AMR) is recognized as a major cause of graft loss in renal transplant recipients. Early acute AMR in the first few days after transplantation occurs primarily in sensitized renal transplant recipients with donor-specific alloantibody at the time of transplant and is a relatively "pure" form of acute AMR. Late acute AMR occurs months to years after transplantation and is commonly a mixed cellular and humoral rejection. While there is no consensus regarding optimum treatment, we contend that rational therapeutic approaches are emerging and the acute episode can be managed in most instances...
June 2014: Current Transplantation Reports
Tristan Legris, Christophe Picard, Dilyana Todorova, Luc Lyonnet, Cathy Laporte, Chloé Dumoulin, Corinne Nicolino-Brunet, Laurent Daniel, Anderson Loundou, Sophie Morange, Stanislas Bataille, Henri Vacher-Coponat, Valérie Moal, Yvon Berland, Francoise Dignat-George, Stéphane Burtey, Pascale Paul
Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs). The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR) of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK) cells as innate immune effectors of antibody-dependent cellular cytotoxicity (ADCC), but few studies have investigated their alloreactive potential in the context of solid organ transplantation...
2016: Frontiers in Immunology
Lionel Rostaing, Béatrice Karam, Nicolas Congy-Jolivet, Valérie Hage, Federico Sallusto, Laure Esposito, Nicolas Doumerc, Bénédicte Debiol, Céline Guilbeau-Frugier, Xavier Game, Asma Allal, Nassim Kamar
Few studies have assessed the outcomes of ABOi/HLAi living-kidney transplantation. We report a single-center experience of 12 ABOi/HLAi living-kidney recipients. Twenty-seven donor-specific alloantibodies (DSAs) (1-6 per patient) were found with fluorescence intensities of 1500-15 000. Desensitization was based on IVIg, two doses of rituximab (375 mg/m(2) ), tacrolimus-based (0.2 mg/kg) immunosuppression (started on day-10 pretransplant), and 11 (6-27) pretransplant apheresis sessions (plasmapheresis, specific or semi-specific immunoadsorption)...
April 13, 2016: Therapeutic Apheresis and Dialysis
Sharon Phillips, Meghan Kapp, Deborah Crowe, Jorge Garces, Agnes B Fogo, Giovanna A Giannico
Antibody-mediated rejection (ABMR) is implicated in 45% of renal allograft failure and 57% of late allograft dysfunction. Peritubular capillary C4d is a specific but insensitive marker of ABMR. The 2013 Banff Conference ABMR revised criteria included C4d-negative ABMR with evidence of endothelial-antibody interaction. We hypothesized that endothelial activation and lymphangiogenesis are increased with C4d-negative ABMR and correlate with intragraft T-regulatory cells and T-helper 17. Seventy-four renal transplant biopsies were selected to include (a) ABMR with C4d Banff scores ≥2 (n = 35), (b) variable microvascular injury and C4d score 0-1 (n = 24), and (c) variable microvascular injury and C4d score = 0 (n = 15)...
May 2016: Human Pathology
Hyeyoung Lee, Ji Won Min, Ji-Il Kim, In-Sung Moon, Ki-Hyun Park, Chul Woo Yang, Byung Ha Chung, Eun-Jee Oh
With the development of the single antigen beads assay, the role of donor specific alloantibody (DSA) against human leukocyte antigens in kidney transplantation (KT) has been highlighted. This study aimed to investigate the clinical significance of DQ-DSA detected at renal allograft biopsy. We evaluated 263 KT recipients who underwent allograft biopsy and DSA detection at the same time. Among them, 155 patients who were nonsensitized before transplantation were selected to investigate the role of de-novo DQ-DSA...
March 2016: Medicine (Baltimore)
José Manuel Arreola-Guerra, Marcos Serrano, Luis E Morales-Buenrostro, Mario Vilatobá, Josefina Alberú
BACKGROUND: Use of tacrolimus (TAC) is pivotal to renal transplant (RT) immunosuppressive maintenance regimens. The aim of this study was to evaluate the relationship between TAC trough levels and the development of acute rejection (AR). MATERIAL AND METHODS: This was a retrospective cohort study. We included recipients transplanted between 01/2008 and 05/2012. Regression analyses (Cox's proportional hazards model) and sub-analysis of AR and TAC levels over different time periods were performed...
2016: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Adnan Bashir Bhatti, Muhammad Usman
The global prevalence of renal transplants is increasing with time, and renal transplantation is the only definite treatment for end-stage renal disease. We have limited the acute and late acute rejection of kidney allografts, but the long-term survival of renal tissues still remains a difficult and unanswered question as most of the renal transplants undergo failure within a decade of their transplantation. Among various histopathological changes that signify chronic allograft nephropathy (CAN), tubular atrophy, fibrous thickening of the arteries, fibrosis of the kidney interstitium, and glomerulosclerosis are the most important...
2015: Curēus
Imad Abboud, Marie-noelle Peraldi, Denis Glotz
ABC-incompatible (ABOi) living donor renal transplantation is being developed since the 80s, and may provide a significant source of organs. Blood group A and B antigens are expressed not only on red blood cells but also on renal vascular endothelial and renal epithelial membranes. Each individual has preformed natural antibodies against his/ her absent A and/or B antigens. These antibodies may directly damage the ABOi allograft and cause its diffuse thrombosis and primary non-function. ABOi allogratf recipients are conditioned with one dose of rituximab (as a "pharmacological splenectomy") and oral immunosuppressive treatment is introduced several days pre-operatively...
July 2015: Le Journal Médical Libanais. the Lebanese Medical Journal
Hiba Azar, Chebl Mourani, Dania Nehme Chelala, Maroun Moukarzel
Kidney transplantation is now accepted to be the best treatment for end-stage renal disease. Despite the improvement of immunosuppressive therapy, there is still actually substantial loss of allografts, in part due to uncontrolled humoral immunity. For many years, the primary technique for the detection of anti-HLA antibodies was the CDC (complement dependent cytotoxicity). The recent use of solid phase assays, mainly the Luminex technology allowed detection of antibodies at much lower levels, and it has been shown that these antibodies have negative impact on the graft survival...
July 2015: Le Journal Médical Libanais. the Lebanese Medical Journal
Germaine Wong, Samantha Chua, Steven J Chadban, Philip Clayton, Helen Pilmore, Peter D Hughes, Paolo Ferrari, Wai H Lim
BACKGROUND: The number of patients with end-stage renal disease being relisted for a second kidney transplant is increasing worldwide. The aim of this study was to determine the relationship between waiting time for a second transplant and outcomes after that second transplant. METHODS: Using Australia and New Zealand Dialysis and Transplant registry, patients who have received second kidney transplants between 1997 and 2009 were included. The associations between waiting time, defined as duration of dialysis between first allograft failure and second transplantation, and clinical outcomes including acute rejection, graft and patient survival were examined using adjusted logistic and Cox regression models...
August 2016: Transplantation
Anja Lemke, Mercedes Noriega, Anja M Röske, Markus J Kemper, Björn Nashan, Christine S Falk, Martina Koch
BACKGROUND: Acute renal allograft rejection remains a major cause of allograft dysfunction; especially for episodes with mixed humoral and cellular character which can be detrimental for graft survival. We established a rat RT model with exclusive and complete MHC-disparity to investigate pathomechanisms of acute rejection and evaluate serum multiplex assays as a diagnostic tool in this context. METHODS: LEW rats receive congeneic LEW.1W allografts (allo), no immunosuppression...
October 2015: Transplant Immunology
Rachel Z C Teo, Germaine Wong, Graeme R Russ, Wai H Lim
AIMS: Rejection of renal allografts following transplantation continues to be a major impediment to long-term graft survival. Although acute vascular rejection (AVR) is associated with a high risk of graft loss, it remains unclear whether AVR with accompanied cellular or acute humoral rejection (AHR) have dissimilar outcomes. The aim of this registry study was to examine the association between subtypes of AVR and graft loss. METHODS: Using Australia and New Zealand Dialysis and Transplant registry, primary kidney transplant recipients between 2005 and 2012 whose first rejection episode was AVR were included and categorized into AVR-none (AVR without other rejections), AVR-CG (AVR with cellular and/or glomerular rejections), and AVR-AHR (AVR with AHR)...
February 2016: Nephrology
Balázs Nemes, Zsolt Kanyári, Gergely Zádori, Lajos Zsom, Mariann Berhés, Mátyás Hamar, Krisztina Kóbor, Antal Péter
Horseshoe kidney is a fusion anomaly found in approximately one in 400-600 people. Due to vascular and ureteral variations, transplantation with a horseshoe kidney presents a technical challenge. In our case, the isthmus connected the upper poles and contained parenchyma. It consisted of three renal arteries, five veins collected to the inferior vena cava, and two ureters and pyelons. It was implanted en bloc to the left side retroperitoneally. During the early period, cellular and humoral rejection was confirmed and treated...
June 2015: Interventional Medicine & Applied Science
Ken Sugiyama, Yoji Hyodo, Atsushi Aikawa
OBJECTIVE: To assess changes in anti-blood type antibody titers and postoperative outcomes (graft survival and rejection rates) at our center with the use of the immunosuppressant, rituximab, in ABO-incompatible kidney transplants from living donors. Confirming anti-donor blood group antibodies is important for avoiding humoral rejection in ABO-incompatible kidney transplants. Splenectomy has been carried out in our hospital according to Alexandre's policy in order to suppress the production of anti-donor blood group antibodies...
October 2015: International Journal of Urology: Official Journal of the Japanese Urological Association
James I Kim, David M Rothstein, James F Markmann
PURPOSE OF REVIEW: B cells are known to play a central role in humoral immunity and to boost cellular immunity, however, in a variety of experimental models, B-cell subsets ameliorate inflammation and autoimmune disease, indicating that they can also play a regulatory role. Here, we highlight the advances in regulatory B-cell (Breg) biology of the past year with an emphasis on findings pertinent to transplantation. Several recent observations highlight the relevance to clinical transplantation...
August 2015: Current Opinion in Organ Transplantation
S Querido, D Machado, C Silva, F Nolasco, A Nunes, S Sampaio, P Cruz, C Oliveira, A Weigert
INTRODUCTION: With the introduction of combination antiretroviral therapy (cART), prognosis of human immunodeficiency virus (HIV) infection has been improved and kidney transplantation (KT) in HIV-positive patients became possible. METHODS: We reviewed the demographic, clinical, laboratory, and therapeutic data of all the HIV-infected patients who underwent KT between 2009 (first KT in Portugal in a HIV-infected patient) and May 2014. Case accrual was through all Portuguese KT centers where a KT in an HIV-infected patient was performed...
May 2015: Transplantation Proceedings
Yong-Hun Sin, Yong-Jin Kim, Joon Seok Oh, Jin Ho Lee, Seong Min Kim, Joong Kyung Kim
Here we report the successful treatment of acute antibody-mediated rejection (AMR) with bortezomib. Bortezomib rescue treatment was administered after a 42-year-old woman failed to respond to steroid pulse and plasmapheresis with intravenous immunoglobulin (IVIG). The patient underwent a second renal transplantation with a deceased donor kidney. She was treated pre-operatively with rituximab (200 mg/body) and underwent plasmapheresis twice (day-1 and operation day) because ELISA screening revealed that her pre-operative peak panel reactive antibody (PRA) composition was 100% class I and 100% class II and 15 times of cross-match positive history during the waiting period for transplantation...
July 2015: Nephrology
Takahiro Tsuji, Mitsuru Yanai, Hiroe Itami, Yasushi Ishii, Mayuko Akimoto, Nobuyuki Fukuzawa, Hiroshi Harada, Yuichiro Fukasawa
AIM: Chronic active antibody-mediated rejection (chronic ABMR) is one important cause of late-stage renal allograft loss. However, few reports have used protocol biopsy to observe changes over time in cases that develop chronic ABMR. The aim of this study was to use protocol biopsy to clarify the histological features of cases that develop chronic ABMR. METHODS: We recruited 379 ABO compatible patients who underwent protocol biopsy at our hospital from 2010 to 2014...
July 2015: Nephrology
Tomokazu Shimizu, Hiroshi Toma, Rumi Shibahara, Kuniko Tsunoyama, Junpei Izuka, Taiji Nozaki, Hideki Ishida, Kazunari Tanabe, Kazuho Honda, Junki Koike
AIM: We discuss the clinicopathological analysis of cases of chronic vascular rejection (CVR) cases after renal transplantation and clarify the mechanisms underlying the development and prognostic significance of CVR. PATIENTS: CVR was diagnosed in 46 renal allograft biopsy specimens (BS) obtained from 34 renal transplant patients being followed up at the Department of Urology, Tokyo Women's Medical University, between January 2009 and December 2013. RESULTS: CVR was diagnosed at a median of 47...
July 2015: Nephrology
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