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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28088367/assignment-of-c1q-binding-hla-antibodies-as-unacceptable-hla-antigens-avoids-positive-cdc-crossmatches-prior-to-transplantation-of-deceased-donor-organs
#15
David Juhl, Matthias Marget, Michael Hallensleben, Siegfried Görg, Malte Ziemann
Soon, a virtual crossmatch shall replace the complement-dependent cytotoxicity (CDC) allocation crossmatch in the Eurotransplant region. To prevent positive CDC-crossmatches in the recipient centre, careful definition of unacceptable antigens is necessary. For highly sensitized patients, this is difficult by CDC alone. Assignment of all antibodies detected by sensitive assays, however, could prevent organ allocation. To assess the usefulness of the Luminex C1q-assay to prevent positive CDC-crossmatches, all CDC-crossmatches performed prior to deceased kidney transplantation in a 16-month-period were reviewed...
January 12, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28058212/complement-related-kidney-diseases-recurrence-after-transplantation
#16
REVIEW
Maurizio Salvadori, Elisabetta Bertoni
The recurrence of renal disease after renal transplantation is becoming one of the main causes of graft loss after kidney transplantation. This principally concerns some of the original diseases as the atypical hemolytic uremic syndrome (HUS), the membranoproliferative glomerulonephritis (MPGN), in particular the MPGN now called C3 glomerulopathy. Both this groups of renal diseases are characterized by congenital (genetic) or acquired (auto-antibodies) modifications of the alternative pathway of complement...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28017877/negative-regulation-of-hla-dr-expression-on-endothelial-cells-by-anti-blood-group-a-b-antibody-ligation-and-mtor-inhibition
#17
Kenta Iwasaki, Yuko Miwa, Kazuharu Uchida, Yasuhiro Kodera, Takaaki Kobayashi
Donor-specific antibody (DSA), particularly against HLA class II, is a major cause of chronic antibody-mediated rejection (CAMR) after transplantation, although ABO-incompatible kidney transplantation has recently demonstrated favorable graft outcomes. The condition of no injury even in the presence of anti-donor antibody has been referred to as "accommodation", which would be one of the key factors for successful long-term graft survival. The purpose of this study was to analyze the beneficial effect of anti-blood group A/B antibody ligation on endothelial cells against HLA-DR antibody-mediated, complement-dependent cytotoxicity (CDC)...
December 23, 2016: Transplant Immunology
https://www.readbyqxmd.com/read/27932097/desensitization-protocol-in-recipients-of-deceased-kidney-donor-with-donor-specific-antibody-low-titers
#18
J Kanter Berga, A Sancho Calabuig, E Gavela Martinez, N Puig Alcaraz, A Avila Bernabeu, J Crespo Albiach, P Molina Vila, S Beltrán Catalan, L Pallardó Mateu
BACKGROUND: Kidney transplantation is the better option for end-stage renal disease (ESRD), but for patients with human leukocyte antigen (HLA) sensitization, the wait times are significantly longer than for patients without antibodies. Many desensitization protocols have been described involving strong immunosuppression, the use of apheresis, and B-cell-modulating therapies. We have designed a desensitization protocol from day 0 for deceased donor kidney transplantation. Our aim was to present our initial experience with five kidney transplant patients...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27914702/renal-xenotransplantation-experimental-progress-and-clinical-prospects
#19
Martin Wijkstrom, Hayato Iwase, Wayne Paris, Hidetaka Hara, Mohamed Ezzelarab, David K C Cooper
There are >100,000 patients waiting for kidney transplants in the United States and a vast need worldwide. Xenotransplantation, in the form of the transplantation of kidneys from genetically engineered pigs, offers the possibility of overcoming the chronic shortage of deceased and living human donors. These genetic manipulations can take the form of (i) knockout of pig genes that are responsible for the expression of antigens against which the primate (human or nonhuman primate) has natural "preformed" antibodies that bind and initiate complement-mediated destruction or (ii) the insertion of human transgenes that provide protection against the human complement, coagulation, or inflammatory responses...
April 2017: Kidney International
https://www.readbyqxmd.com/read/27894836/use-of-complement-binding-assays-to-assess-the-efficacy-of-antibody-mediated-rejection-therapy-and-prediction-of-graft-survival-in-kidney-transplantation
#20
Daniel S Ramon, Yihung Huang, Lili Zhao, TrisAnn Rendulic, Jeong M Park, Randall S Sung, Milagros Samaniego
BACKGROUND: The Luminex® single antigen bead assay (SAB) is the method of choice for monitoring the treatment for antibody-mediated rejection (AMR). A ⩾50% reduction of the dominant donor-specific antibody (IgG-DSA) mean fluorescence intensity (MFI) has been associated with improved kidney allograft survival, and C1q-fixing DSA activity is associated with poor outcomes in patients with AMR. We aimed to investigate if C1q-DSA can be used as a reliable predictor of response to therapy and allograft survival in patients with biopsy-proven AMR...
February 2017: Human Immunology
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