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donor specific antibodies post renal transplant

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https://www.readbyqxmd.com/read/28339671/characteristics-of-donor-specific-anti-hla-antibodies-and-outcome-in-renal-transplant-patients-treated-with-a-standardized-induction-regimen
#1
Daniel Zecher, Christian Bach, Christoph Staudner, Carsten A Böger, Tobias Bergler, Bernhard Banas, Bernd M Spriewald
Background.: Pre-transplant donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have been associated with antibody-mediated rejection (AMR) and early kidney allograft loss. Uncertainties remain regarding the general applicability of these findings and the optimal induction therapy in DSA-positive patients. Methods.: Pre-transplant sera from 174 patients receiving a crossmatch-negative kidney transplant were retrospectively analysed for DSA using Luminex technology...
February 18, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28242033/a-composite-score-associated-with-spontaneous-operational-tolerance-in-kidney-transplant-recipients
#2
Richard Danger, Mélanie Chesneau, Chloé Paul, Pierrick Guérif, Maxim Durand, Kenneth A Newell, Sai Kanaparthi, Laurence A Turka, Jean-Paul Soulillou, Rémi Houlgatte, Magali Giral, Gérard Ramstein, Sophie Brouard
New challenges in renal transplantation include using biological information to devise a useful clinical test for discerning high- and low-risk patients for individual therapy and ascertaining the best combination and appropriate dosages of drugs. Based on a 20-gene signature from a microarray meta-analysis performed on 46 operationally tolerant patients and 266 renal transplant recipients with stable function, we applied the sparse Bolasso methodology to identify a minimal and robust combination of six genes and two demographic parameters associated with operational tolerance...
February 24, 2017: Kidney International
https://www.readbyqxmd.com/read/28236636/re-evaluation-of-glomerulitis-using-occlusion-criteria-based-on-the-banff-2013-revision
#3
Yasemin Ozluk, Yasar Caliskan, Mustafa Sevinc, Aysel Bayram, Evsen Apaydin Arikan, Aydin Turkmen, Sebahat Akgul, Fatma Oguz Savran, Mehmet Sukru Sever, Isin Kilicaslan
The presence of occlusion/near-occlusion of glomerular capillaries was recently added to the existing definition of glomerulitis (g). We retrospectively re-evaluated 135 renal allograft biopsies regarding g to ensure no antibody-damaged grafts were missed. Previous and revised g scores (pg and rg, respectively) were compared for clinicopathologic correlations. The g score did not change in 100 (74.1%) biopsies. Thirty-five (25.9%) biopsies were changed to a lower score. Sensitivity and specificity of pg and rg for the presence of donor specific antibodies (DSA) were 76% vs...
February 25, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28211192/racial-differences-in-incident-de-novo-donor-specific-anti-hla-antibody-among-primary-renal-allograft-recipients
#4
Matthew J Everly, Kimberly P Briley, Carl E Haisch, Georg Dieplinger, Paul Bolin, Scott A Kendrick, Claire Morgan, Angela Q Maldonado, Lorita M Rebellato
Controversy exists as to whether African American (AA) transplant recipients are at risk for developing de novo donor-specific anti-human leukocyte antigen (HLA) antibody (dnDSA). We studied 341 HLA-mismatched, primary renal allograft recipients who were consecutively transplanted between 3/1999 and 12/2010. Sera were collected sequentially pre- and post-transplant and tested for anti-HLA immunoglobulin G (IgG) via single antigen bead assay. Of the 341 transplant patients (225 AA and 116 non-AA), 107 developed dnDSA at a median of 9...
February 17, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28199785/assessment-of-tocilizumab-anti-il-6-receptor-monoclonal-as-a-potential-treatment-for-chronic-antibody-mediated-rejection-and-transplant-glomerulopathy-in-hla-sensitized-renal-allograft-recipients
#5
Jua Choi, Olivier Aubert, Ashley Vo, Alexandre Loupy, Mark Haas, Dechu Puliyanda, Irene Kim, Sabrina Louie, Alexis Kang, Alice Peng, Joe Kahwaji, Nancy Reinsmoen, Mieko Toyoda, Stanley C Jordan
Extending the functional integrity of renal allografts is the primary goal of transplant medicine. Development of donor-specific antibodies (DSAs) post-transplant leads to chronic active antibody-mediated rejection (cABMR) and transplant glomerulopathy (TG), resulting in the majority of graft losses in the U.S. This reduces the quality & length of life for patients and increases cost. There are no approved treatments for cABMR. Evidence suggests the pro-inflammatory cytokine interleukin 6 (IL-6) may play an important role in DSA generation and cABMR...
February 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28199784/allosensitization-following-bone-graft
#6
Eoin D O'Sullivan, Richard K Battle, Sharon Zahra, John F Keating, Lorna P Marson, David M Turner
It is recognised that patients may become sensitized to donor-specific HLA antigens as a result of previous antigenic exposures, classically through previous transplantation, pregnancy or blood transfusion. We present an unusual case of a patient who unexpectedly developed a range of anti-HLA antibodies following orthopaedic surgery where a bone graft was deployed intraoperatively. We describe the case of a 52-year-old male awaiting a renal transplantation, undergoing elective orthopaedic surgery requiring a small volume bone graft...
February 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28104301/differences-in-pathologic-features-and-graft-outcomes-in-antibody-mediated-rejection-of-renal-allografts-due-to-persistent-recurrent-versus-de-novo-donor-specific-antibodies
#7
Mark Haas, James Mirocha, Nancy L Reinsmoen, Ashley A Vo, Jua Choi, Joseph M Kahwaji, Alice Peng, Rafael Villicana, Stanley C Jordan
Antibody-mediated rejection (ABMR) of renal allografts occurs in two forms. Type 1 ABMR results from persistence and/or a rebound of preexisting donor-specific antibodies in sensitized patients and usually occurs early post-transplantation. Type 2 ABMR is associated with de novo donor-specific antibodies and usually occurs over one year post-transplantation. It is generally accepted that types 1 and 2 also differ with regard to certain pathologic features including the frequencies of C4d positivity and concurrent cell-mediated rejection...
January 16, 2017: Kidney International
https://www.readbyqxmd.com/read/28027625/early-conversion-from-calcineurin-inhibitor-to-everolimus-based-therapy-following-kidney-transplantation-results-of-the-randomized-elevate-trial
#8
Johan W de Fijter, Hallvard Holdaas, Ole Øyen, Jan-Stephan Sanders, Sankaran Sundar, Frederike J Bemelman, Claudia Sommerer, Julio Pascual, Yingyos Avihingsanon, Cholatip Pongskul, Frederic Oppenheimer, Lorenzo Toselli, Graeme Russ, Zailong Wang, Patricia Lopez, Jossy Kochuparampil, Josep M Cruzado, Markus van der Giet
In a 24-month, multicenter, open-label, randomized trial, 715 de novo kidney transplant recipients were randomized at 10-14 weeks to convert to everolimus (n=359) or remain on standard calcineurin inhibitor (CNI) therapy (n=356; 231 tacrolimus; 125 cyclosporine), all with mycophenolic acid and steroids. The primary endpoint, change in estimated GFR from randomization to month 12, was similar for everolimus versus CNI: mean (SE) 0.3(1.5)mL/min/1.73(2) versus -1.5(1.5)mL/min/1.73(2) (p=0.116). At month 24, mean (SD) estimated GFR was 62...
December 27, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27900974/disseminated-mycobacteria-chelonae-infection-in-a-kidney-pancreas-transplant-recipient-a-case-report-and-review-of-the-literature
#9
Shafi Malik, Ananda Ghosh, Shahid Husain
A 40-year-old male with a long-standing history of type 1 diabetes with end-stage renal failure underwent combined kidney-pancreas (KP) transplant from a standard criteria donor. Post-operative course was uncomplicated with good primary function of both transplant grafts. Induction was with thymoglobulin and maintenance immunosuppression was with tacrolimus, mycophenolate mofetil and prednisolone. Nine weeks post-transplant, the patient developed dysfunction of both grafts. Panel reactive antibody testing revealed that the patient had developed a de novo donor-specific antibody and considering an antibody-mediated rejection the patient was treated with intravenous pulse methyl prednisone 500 mg ×3 doses, IV immunoglobulin 2 mg/kg in two divided doses, and ATG 7 mg/kg (total dose of 700 mg)...
November 2016: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/27871759/rabbit-atg-or-basiliximab-induction-for-rapid-steroid-withdrawal-after-renal-transplantation-harmony-an-open-label-multicentre-randomised-controlled-trial
#10
Oliver Thomusch, Michael Wiesener, Mirian Opgenoorth, Andreas Pascher, Rainer Peter Woitas, Oliver Witzke, Bernd Jaenigen, Markus Rentsch, Heiner Wolters, Thomas Rath, Tülay Cingöz, Urs Benck, Bernhard Banas, Christian Hugo
BACKGROUND: Standard practice for immunosuppressive therapy after renal transplantation is quadruple therapy using antibody induction, low-dose tacrolimus, mycophenolate mofetil, and corticosteroids. Long-term steroid intake significantly increases cardiovascular risk factors with negative effects on the outcome, especially post-transplantation diabetes associated with morbidity and mortality. In this trial, we examined the efficacy and safety parameters of rapid steroid withdrawal after induction therapy with either rabbit antithymocyte globulin (rabbit ATG) or basiliximab in immunologically low-risk patients during the first year after kidney transplantation...
December 17, 2016: Lancet
https://www.readbyqxmd.com/read/27870356/clinical-and-immunological-relevance-of-antibodies-in-solid-organ-transplantation
#11
REVIEW
N K Mehra, A K Baranwal
The two important issues affecting recipients of solid organ transplants and of importance to immunologists are (i) sensitization of the recipient to HLA antigens and the resultant humoral immune response leading to the development of anti-HLA antibodies; and ii) development of robust assays for early detection of humoral rejection post-transplant. Evidence from several studies clearly indicates that presence of circulating anti-HLA antibodies especially donor specific leads to early graft loss and high titres of DSA may even lead to hyperacute or accelerated acute rejection...
December 2016: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/27639190/early-conversion-to-prednisolone-everolimus-as-an-alternative-weaning-regimen-associates-with-beneficial-renal-transplant-histology-and-function-the-randomized-controlled-mecano-trial
#12
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
https://www.readbyqxmd.com/read/27545900/a-chronic-renal-rejection-model-with-a-fully-mhc-mismatched-rat-strain-combination-under-immunosuppressive-therapy
#13
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
https://www.readbyqxmd.com/read/27543781/non-hla-matched-3rd-party-vascular-allograft-in-renal-transplant-may-lead-to-sensitization-against-donor-hla
#14
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
https://www.readbyqxmd.com/read/27539748/evaluation-of-c1q-status-and-titer-of-de-novo-donor-specific-antibodies-as-predictors-of-allograft-survival
#15
C Wiebe, A J Gareau, D Pochinco, I W Gibson, J Ho, P E Birk, T Blydt-Hansen, 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...
March 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/27502290/identification-of-patients-at-risk-for-renal-impairment-after-living-donor-kidney-transplantation
#16
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...
December 2016: Langenbeck's Archives of Surgery
https://www.readbyqxmd.com/read/27327607/incidence-and-impact-of-anti-hla-dp-antibodies-in-renal-transplantation
#17
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
https://www.readbyqxmd.com/read/27137749/donor-specific-antibodies-present-at-the-time-of-kidney-transplantation-in-immunologically-unmodified-patients-increase-the-risk-of-acute-rejection
#18
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
https://www.readbyqxmd.com/read/27089840/donor-specific-hla-antibodies-and-graft-function-in-kidney-transplanted-children-the-vienna-cohort
#19
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
https://www.readbyqxmd.com/read/27048228/bortezomib-may-stabilize-pediatric-renal-transplant-recipients-with-antibody-mediated-rejection
#20
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
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