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donor specific antibodies post renal transplant

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https://www.readbyqxmd.com/read/28736013/outcomes-of-highly-sensitized-patients-undergoing-simultaneous-liver-and-kidney-transplantation-a-single-center-experience-with-desensitization
#1
J A Steggerda, A Kang, S-H Pan, V Sundaram, N N Nissen, A S Klein, T Todo, A Annamalai, A Vo, S C Jordan, I K Kim
BACKGROUND: Preformed donor-specific human leukocyte antigen antibodies (DSAs) in patients undergoing simultaneous liver and kidney transplantation (SLKT) are an independent risk factor for poorer patient and renal allograft survival. The outcomes of patients highly sensitized (HS) against HLA antigens undergoing SLKT and select HS SLKT recipients undergoing desensitization at a high-volume desensitization center were investigated. METHODS: Seventy-five patients undergoing SLKT at a high-volume desensitization center between January 1, 2001, and December 31, 2015, were retrospectively reviewed...
July 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28679466/successful-launch-of-an-abo-incompatible-kidney-transplantation-program-to-overcome-the-shortage-of-compatible-living-donors-experience-at-a-single-center%C3%A2
#2
Seung Hwan Song, Juhan Lee, Beom Seok Kim, Sinyoung Kim, Jae Geun Lee, Hyeon Joo Jeong, Yu Seun Kim, Myoung Soo Kim, Hyun Ok Kim, Soon Il Kim, Kyu Ha Huh
AIMS: ABO-incompatible (ABOi) kidney transplantation (KT) is being increasingly performed to overcome donor shortages. However, debate persists regarding the post-transplant outcomes of ABOi KT vs. that of ABO-compatible (ABOc) KT. METHODS: A total 454 recipients who underwent living-donor KT (LDKT) between June 2010 and July 2014 at Severance Hospital (Seoul) were retrospectively reviewed. 100 ABOi and 354 ABOc KTs were compared. Recipients with a pretransplant positive crossmatch to their donors, pretransplant donor-specific anti-HLA antibody (DSA), or high panel reactive antibody (PRA ≥ 50%) were excluded from both the ABOi and ABOc KT groups...
September 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28671951/an-adjustable-predictive-score-of-graft-survival-in-kidney-transplant-patients-and-the-levels-of-risk-linked-to-de-novo-donor-specific-anti-hla-antibodies
#3
Aurélie Prémaud, Matthieu Filloux, Philippe Gatault, Antoine Thierry, Matthias Büchler, Eliza Munteanu, Pierre Marquet, Marie Essig, Annick Rousseau
Most predictive models and scores of graft survival in renal transplantation include factors known before transplant or at the end of the first year. They cannot be updated thereafter, even in patients developing donor-specific anti-HLA antibodies and acute rejection.We developed a conditional and adjustable score for prediction of graft failure (AdGFS) up to 10 years post-transplantation in 664 kidney transplant patients. AdGFS was externally validated and calibrated in 896 kidney transplant patients.The final model included five baseline factors (pretransplant non donor-specific anti-HLA antibodies, donor age, serum creatinine measured at 1 year, longitudinal serum creatinine clusters during the first year, proteinuria measured at 1 year), and two predictors updated over time (de novo donor-specific anti-HLA antibodies and first acute rejection)...
2017: PloS One
https://www.readbyqxmd.com/read/28629951/immunogenicity-of-class-i-hla-but-not-preformed-low-mfi-donor-specific-antibodies-correlates-with-outcomes-after-first-renal-transplantation
#4
A Lobashevsky, W Goggins, K Rosner, T Taber
BACKGROUND: The role of low levels of circulating donor specific antibodies (DSA) producing negative flow cytometry cross match is not completely defined. The purpose of this study was to examine the clinical significance of preexisting low levels of class I DSAs in flow cytometry cross match (FC CM) negative first kidney transplant recipients (KTRs). METHODS: All of the KTRs (n=41) had low levels of anti-class I antibodies only. The kidney transplant outcome was evaluated by the development of a deleterious effect (DE) in recipients in the study cohort (Group 1: DE+, Group 2: DE-)...
June 16, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28582797/the-detrimental-impact-of-persistent-vs-an-isolated-occurrence-of-de-novo-donor-specific-antibodies-on-intermediate-term-renal-transplant-outcomes
#5
Jennifer M Loucks-DeVos, Todd N Eagar, A Osama Gaber, Samir J Patel, Larry D Teeter, Edward A Graviss, Richard J Knight
BACKGROUND: De novo donor-specific antibodies (dnDSA) after renal transplant are associated with acute rejection (AR) and graft loss, yet most recipients with dnDSA have stable function and no AR. We assessed whether the persistence of dnDSA increased the risk of a detrimental outcome. METHODS: A single-center review of renal transplant recipients monitored for dnDSA at multiple time points post-transplant. An Isolated dnDSA was defined as one positive dnDSA and no additional positive tests, whereas ≥2 positive dnDSA was defined as persistent dnDSA...
June 5, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28457920/antibody-response-to-hbv-vaccination-on-dialysis-does-not-correlate-with-the-development-of-denovo-anti-hla-antibodies-after-renal-transplantation
#6
Teresa Kauke, Maximilian Link, Markus Rentsch, Manfred Stangl, Markus Guba, Joachim Andrassy, Jens Werner, Bruno Meiser, Michael Fischereder, Antje Habicht
BACKGROUND: Response to Hepatitis B virus (HBV) vaccination can be diminished in some (50-80%) but not all dialysis patients. We hypothesized, that the response to vaccination on dialysis may correlate with the development of anti-HLA antibodies after renal transplantation and might therefore be a valuable parameter to predict alloresponses. METHODS: The response to HBV vaccination on dialysis and the development of deNovo anti-HLA antibodies post-transplant was analyzed in 188 non-immunized renal transplant recipients...
June 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28457402/early-vascular-thrombosis-after-kidney-transplantation-can-we-predict-patients-at-risk
#7
R A P de Freitas, M L de Lima, M Mazzali
BACKGROUND: Renal transplant is the therapy of choice for patients with chronic renal disease. In recent years, improvement in immunosuppressive drugs reduced early graft loss associated with acute rejection. However, vascular thrombosis, accounting for 5% of early graft loss, can sensitize the recipient for human leukocyte antibodies, reducing the chance for a second transplant. The aim of this study was to identify risk factors for vascular thrombosis in a single transplant center, to design specific prevention protocol...
May 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28372986/assessing-the-potential-of-angiotensin-ii-type-1-receptor-and-donor-specific-anti-endothelial-cell-antibodies-to-predict-long-term-kidney-graft-outcome
#8
David F Pinelli, John J Friedewald, Kelley M K Haarberg, Shree L Radhakrishnan, Jennifer R Zitzner, Wendy E Hanshew, Anat R Tambur
Endothelial cell antigens have been reported as potential targets for antibodies in the context of organ transplantation, leading to increased risk for graft failure. Serum samples from 142 consecutive living donor kidney recipients were tested for the presence of antibodies to angiotensin II - type 1 receptor (AT1R), donor endothelial cells, and donor HLA. Graft survival was monitored for five years post-transplant, and secondary outcomes, including biopsy-proven rejection, proteinuria, biopsy-proven vasculopathy, and renal function based on serum creatinine were also assessed for the first two to three years...
March 31, 2017: Human Immunology
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
#9
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...
April 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28242033/a-composite-score-associated-with-spontaneous-operational-tolerance-in-kidney-transplant-recipients
#10
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...
June 2017: Kidney International
https://www.readbyqxmd.com/read/28236636/re-evaluation-of-glomerulitis-using-occlusion-criteria-based-on-the-banff-2013-revision-a-retrospective-study
#11
Yasemin Ozluk, Yasar Caliskan, Mustafa Sevinc, Aysel Bayram, Evsen A Arikan, Aydin Turkmen, Sebahat Akgul, Fatma O Savran, Mehmet S 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-results-from-a-single-center-cohort-study
#12
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 leucocyte 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-interleukin-6-receptor-monoclonal-as-a-potential-treatment-for-chronic-antibody-mediated-rejection-and-transplant-glomerulopathy-in-hla-sensitized-renal-allograft-recipients
#13
J Choi, O Aubert, A Vo, A Loupy, M Haas, D Puliyanda, I Kim, S Louie, A Kang, A Peng, J Kahwaji, N Reinsmoen, M Toyoda, S C Jordan
Extending the functional integrity of renal allografts is the primary goal of transplant medicine. The development of donor-specific antibodies (DSAs) posttransplantation leads to chronic active antibody-mediated rejection (cAMR) and transplant glomerulopathy (TG), resulting in the majority of graft losses that occur in the United States. This reduces the quality and length of life for patients and increases cost. There are no approved treatments for cAMR. Evidence suggests the proinflammatory cytokine interleukin 6 (IL-6) may play an important role in DSA generation and cAMR...
February 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28199784/allosensitization-following-bone-graft
#14
E D O'Sullivan, R K Battle, S Zahra, J F Keating, L P Marson, D M Turner
It is recognized 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 orthopedic surgery where a bone graft was deployed intraoperatively. We describe the case of a 52-year-old man awaiting a renal transplantation, undergoing elective orthopedic surgery requiring a small-volume bone graft...
August 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
#15
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
#16
J W de Fijter, H Holdaas, O Øyen, J-S Sanders, S Sundar, F J Bemelman, C Sommerer, J Pascual, Y Avihingsanon, C Pongskul, F Oppenheimer, L Toselli, G Russ, Z Wang, P Lopez, J Kochuparampil, J M Cruzado, M 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 glomerular filtration rate (eGFR) from randomization to month 12, was similar for everolimus versus CNI: mean (standard error) 0.3(1.5) mL/min/1.73(2) versus -1...
July 2017: 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
#17
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
#18
RANDOMIZED CONTROLLED TRIAL
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
#19
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
#20
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)...
April 2017: American Journal of Transplantation
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