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donor specific antibodies post renal transplant

F J Bemelman, J W de Fijter, J Kers, C Meyer, H Peters-Sengers, E F de Maar, K A M I van der Pant, A P J de Vries, J-S Sanders, A Zwinderman, M M Idu, S Berger, M E J Reinders, C Krikke, I M Bajema, M C van Dijk, I J M Ten Berge, J Ringers, J Lardy, D Roelen, D-J Moes, S Florquin, J J Homan van der Heide
In renal transplantation, use of calcineurin inhibitors (CNIs) is associated with nephrotoxicity and immunosuppression with malignancies and infections. This trial aimed to minimize CNI exposure and total immunosuppression while maintaining efficacy. We performed a randomized controlled, open-label multicenter trial with early cyclosporine A (CsA) elimination. Patients started with basiliximab, prednisolone (P), mycophenolate sodium (MPS), and CsA. At 6 months, immunosuppression was tapered to P/CsA, P/MPS, or P/everolimus (EVL)...
September 17, 2016: American Journal of Transplantation
Kaori Hanaoka, Yuka Kawato, Kaori Kubo, Tomonori Nakanishi, Masashi Maeda, Koji Nakamura, Jun Hirose, Takahisa Noto, Hidehiko Fukahori, Akihiko Fujikawa, Sosuke Miyoshi, Shoji Takakura, Tatsuaki Morokata, Yasuyuki Higashi
BACKGROUND: The Fischer-to-Lewis (LEW) rat model of kidney transplantation is a widely accepted and well-characterized model of chronic rejection. In contrast to transplantation in a clinical setting, however, the absence of treatment with immunosuppressants and only minor mismatch of major histocompatibility complexes (MHCs) are critical discrepancies. Here, we established a rat model of chronic rejection using fully MHC-mismatched strains in which kidney disease progresses even under immunosuppressive therapy...
September 2016: Transplant Immunology
Henry Watson, Rupaly Pande, Shahid Farid, Clare Ecuyer, Richard Baker, Brendan Clarke, Niaz Ahmad
3rd party donor vessels are often used for vascular reconstruction in organ transplantation. While current practice ensures that 3rd party vessels are blood group matched, HLA matching to the non-intended recipient is not performed. This practice potentially sensitizes the recipient and may reduce their future chance of renal transplant from a larger pool of donors. We examined our cohort of renal transplant recipients who received non-HLA-matched 3rd party vessels for the de-novo development of donor-specific HLA antibodies...
August 20, 2016: Clinical Transplantation
C Wiebe, A J Gareau, D Pochinco, I W Gibson, J Ho, P E Birk, T Blydt-Hasen, M Karpinski, A Goldberg, L Storsley, D N Rush, P W Nickerson
De novo donor-specific antibodies (dnDSAs) that develop after renal transplantation are independent predictors of allograft loss. However, it is unknown if dnDSA C1q status or titer at the time of first detection can independently predict allograft loss. In a consecutive cohort of 508 renal transplant recipients, 70 developed dnDSAs. Histologic and clinical outcomes were correlated with the C1q assay or dnDSA titer. C1q positivity correlated with dnDSA titer (p < 0.01) and mean fluorescence intensity (p < 0...
August 19, 2016: American Journal of Transplantation
Alexander Kaltenborn, Almut Nolte, Ysabell Schwager, Simon A Littbarski, Nikos Emmanouilidis, Viktor Arelin, Jürgen Klempnauer, Harald Schrem
PURPOSE: Outcome after living donor kidney transplantation is highly relevant, since recipient and donor were exposed to notable harm. Reliable identification of risk factors is necessary. METHODS: Three hundred sixty-six living donor kidney transplants were included in this observational retrospective study. Relevant risk factors for renal impairment 1 year after transplantation and delayed graft function were identified with univariable and multivariable binary logistic regression and ordinal regression analysis...
August 9, 2016: Langenbeck's Archives of Surgery
Mareike Hörmann, Georg Dieplinger, Lorita M Rebellato, Kimberly P Briley, Paul Bolin, Claire Morgan, Carl E Haisch, Matthew J Everly
BACKGROUND: The role of anti-HLA-DP antibodies in renal transplantation is poorly defined. This study describes the impact of donor (donor-specific antibody [DSA]) and non-donor-specific antibodies against HLA-DP antigens in renal transplant patients. METHODS: Of 195 consecutive patients transplanted between September 2009 and December 2011, 166 primary kidney recipients and their donors were typed (high-resolution) for DP antigens. Sera taken pre-transplant and at 1, 3, 6, 9, and 12 months, and annually post-transplant were retrospectively tested for anti-DP antibodies using single-antigen beads...
September 2016: Clinical Transplantation
Aditi Gupta, Daniel Murillo, Sri G Yarlagadda, Connie J Wang, Atta Nawabi, Timothy Schmitt, Michael Brimacombe, Christopher F Bryan
BACKGROUND: Human leukocyte antigens (HLA) class II donor-specific antibodies (DSAs) are associated with microcirculation inflammation, transplant glomerulopathy and ultimately graft loss. There is however no data on allograft outcomes in deceased donor kidney transplant recipients who have not received any desensitization prior to transplantation. METHODS: We prospectively evaluated the association of HLA DR and DQ DSAs on rejection and short-term graft survival in patients who did not receive desensitization prior to transplantation...
July 2016: Transplant Immunology
Krisztina Rusai, Johanna Dworak, Alexandra Potemkina, Gottfried Fischer, Dagmar Csaicsich, Klaus Arbeiter, Christoph Aufricht, Thomas Müller-Sacherer
In the pediatric population, little is known on de novo DSA development, its impact on graft function, and association with suboptimal IS. We assessed the prevalence of de novo DSA in the Vienna cohort of 40 renal transplanted children and adolescents and prospectively followed its association with clinical parameters, graft function, and proteinuria for one yr. At the cross-sectional analysis (median post-transplant time of five yr), 17% of the patients had developed de novo DSA. All HLA-Ab were anti-HLA class II antibodies and persisted in 85% of the cases until the follow-up screening performed within one yr...
June 2016: Pediatric Transplantation
Meghan H Pearl, Anjali B Nayak, Robert B Ettenger, Dechu Puliyanda, Miguel Fernando Palma Diaz, Qiuheng Zhang, Elaine F Reed, Eileen W Tsai
BACKGROUND: Current therapeutic strategies to effectively treat antibody-mediated rejection (AMR) are insufficient. Thus, we aimed to determine the benefit of a therapeutic protocol using bortezomib for refractory C4d + AMR in pediatric kidney transplant patients. METHODS: We examined seven patients with treatment-refractory C4d + AMR. Immunosuppression included antithymocyte globulin or anti-CD25 monoclonal antibody for induction therapy with maintenance corticosteroids, calcineurin inhibitor, and anti-metabolite...
August 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Atsushi Sugitani, Chihiro Takahashi, Takuji Naka, Kazunori Hisamitsu, Osamu Yamamoto, Kenjiro Taniguchi, Naoto Kobayashi, Mari Kimura, Haruhiko Yoshida, Ryuichi Hamazoe
We report a case of tacrolimus vascular toxicity found on a protocol biopsy shortly after a deceased donor renal transplantation. The patient was immunologically high-risk and acute antibody-mediated rejection during post-transplant dialysis phase was suspected on the protocol biopsy. Although the patient was stable after treatment of rejection, a further examination showed a very rare but specific side-effect of tacrolimus. It is sometimes difficult to make a differential diagnosis during postoperative dialysis period among AMR, primary non-functioning, drug toxicity, infection or just prolonged recovery from the damage of a long agonal phase on the non-heart beating donor...
July 2016: Nephrology
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)
Guido Filler, Ana Catalina Alvarez-Elías, Christopher McIntyre, Mara Medeiros
We have reviewed current evidence on the therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) in relationship to drug efficacy and safety. The relationship between actual MPA exposure and mycophenolate mofetil (MMF) dose has been shown to be weak in children and adolescents. The TDM of MPA exposure should ideally be performed using full pharmacokinetic profiles or limited sampling strategies. Recent evidence has provided some rationale for using the post-dose trough level as a single measure. In terms of short-term efficacy, there is strong evidence that a MPA area under the time-concentration curve of >30 mg × h/L reduces acute rejection episodes early after renal transplantation, and there is evolving evidence that aiming for the same exposure over the long term may be a viable strategy to reduce the formation of donor-specific antibodies...
February 26, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Gorden Muduma, Isaac Odeyemi, Jayne Smith-Palmer, Richard F Pollock
UNLABELLED: Antibody-mediated rejection (AbMR) is a leading cause of late graft loss in kidney transplant recipients, accounting for up to 60% of late graft failures. AbMR manifests as two distinct phenotypes: the first occurs in the immediate post-transplant period in sensitized patients; the second occurs in the late post-transplant period and has been associated with non-adherence to immunosuppression. The present review summarizes the current treatment options for AbMR, its clinical and economic burden, and approaches for reducing the risk of AbMR...
March 2016: Advances in Therapy
Xiaomu Zhao, Gang Huang, Simrath Randhawa, Gang Zeng, John Lunz, Parmjeet Randhawa
BACKGROUND: Recent literature has stressed the prominent role of antibodies in graft loss. This study was designed to assess a growing perception that T-cell-mediated rejection (TCMR) is no longer clinically relevant. METHODS: Five hundred forty-five renal allograft recipients over a 3-year period were screened for biopsies with: (a) TCMR including borderline change (BL), (b) negative complement protein C4 degradation fragment, and (c) absence of donor-specific antibody at time of transplant, within 30 days of the biopsy, and up to 4 measurements at later time points...
February 19, 2016: Transplantation
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
Martina Koch, Daniel Poehnert, Bjoern Nashan
AIMS: Chronic renal allograft loss is still an unsolved problem in kidney transplantation. We evaluated the impact of FTY720, a S1P receptor agonist, known to deplete lymphocytes from the peripheral blood by sequestering them into lymph nodes and Peyer's patches, on blood lymphocytes and graft infiltrating cells in a rat model of chronic real allograft rejection. METHODS: LEW rats served as recipients for LEW.1U7B kidney grafts. All animals were treated with CsA (5mg/kg) for 10 days after renal transplantation and monitored for kidney function, peripheral blood lymphocytes and graft infiltrating cells...
March 2016: Transplant Immunology
Kwanchai Pirojsakul, Dev Desai, Chantale Lacelle, Mouin G Seikaly
BACKGROUND: Data on renal allograft outcome in sensitized children are scarce. We report the clinical courses of four children who received desensitization therapy prior to renal transplantation in our institution. METHODS: Between 2009 and 2011, four pediatric patients with stage 5 chronic kidney disease received desensitization therapy due to: (1) positive donor-specific antibodies (DSA) and/or crossmatches with potential living donors, (2) more than three positive crossmatches with deceased donors or (3) high calculated panel-reactive antibody of >80 %...
October 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Ching-Yao Yang, Chih-Yuan Lee, Chi-Chuan Yeh, Meng-Kun Tsai
BACKGROUND/PURPOSE: Desensitization regimens including use of intravenous immune globulin and rituximab have been reported to overcome renal transplant hyperacute rejection. A retrospective case-control study was performed to assess the results and complications of renal transplantation with desensitization therapy for donor-specific antibody (DSA) in a transplant center in Asia, where donor exchange was usually not allowed. METHODS: Between January 2007 and December 2013, 22 patients with DSA received live-donor renal transplantation after desensitization (DSA group)...
December 22, 2015: Journal of the Formosan Medical Association, Taiwan Yi Zhi
Volker Daniel, Mahmoud Sadeghi, Caner Suesal, Sabine Scherer, Hien Tran, Petra Gombos, Karina Trojan, Christian Morath, Gerhard Opelz
BACKGROUND: Literature reports suggest that non-HLA-antibodies against human endothelial progenitor cells (EPC) can be detected in pre-transplant recipient serum and that EPC antibodies can have a deleterious influence on the graft. METHODS: We investigated 71 renal transplant recipients from living donors for a possible influence of pre-transplant donor-specific IgG and/or IgM recipient antibodies against EPC of the donor using the flow cytometric XM-ONE cross-match...
February 2016: Clinical Transplantation
Erika De Sousa-Amorim, Ignacio Revuelta, Fritz Diekmann, Frederic Cofan, Miquel Lozano, Joan Cid, Eduard Palou, Manel Sole, Josep María Campistol, Federic Oppenheimer
AIM: Acute antibody-mediated rejection (ABMR) after kidney transplantation (KT) is associated with poor allograft survival. Current therapies for ABMR are able to deplete B-lymphocytes but do not target plasma cells. Bortezomib is a proteasome inhibitor that can eliminate plasma cells and has demonstrated utility in the treatment of ABMR. METHODS: A retrospective study was carried out from 2010 to 2014, including all patients with ABMR refractory to conventional treatment who received bortezomib...
August 2016: Nephrology
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