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Julie A Houp, Karl P Schillinger, Andrew J Eckstein, Renato M Vega, Niraj M Desai, Bonnie E Lonze, Annette M Jackson
The new Kidney Allocation System (KAS) provides additional allocation points for candidates with broad HLA sensitization in an effort to increase transplant rates for this underserved population. Following the implementation of KAS, our center lowered the HLA antibody threshold for listing unacceptable antigens from a cytotoxicity crossmatch level to a flow cytometric crossmatch level increasing Calculated Panel Reactive Antibody (CPRA) values and allocation points, yet restricting acceptable donor HLA phenotypes...
November 24, 2016: Human Immunology
Rebecca M Garza, Barry H Press, Dolly B Tyan, Yvonne L Karanas, Gordon K Lee
Skin allografts are the benchmark in temporary burn wound coverage, but allografts are hypothesized to place a high antigenic load on recipients. This project aims to determine the degree of human leukocyte antigen sensitization in burn patients treated with allografts. Serum was obtained from nine adult, nontransfused, and nontransplanted burn patients treated with allografts. Group 1 included patients tested in the acute burn period, while group 2 included different patients tested months to years after injury...
October 27, 2016: Journal of Burn Care & Research: Official Publication of the American Burn Association
S Tafulo, J Malheiro, L Dias, C Mendes, E Osório, L S Martins, J Santos, S Pedroso, M Almeida, A Castro-Henriques
The impact of patient's biological differences in waiting time for kidney transplantation is well known and has been a subject of extensive debate and struggle in transplantation community. Our purpose was to evaluate patient's access to kidney transplantation in Portugal, regarding their degree of allosensitization and blood type. A retrospective cohort study including 1020 candidates for kidney transplantation between 01 January 2010 and 31 December 2011 in transplant unit Centro Hospitalar do Porto was performed...
November 2016: HLA
F Torlak, M U S Ayvaci, M E Ahsen, C Arce, M A Vazquez, B Tanriover
BACKGROUND: On December 4, 2014, a new deceased donor kidney allocation system (KAS) was implemented. The KAS was designed to improve organ equity and graft-recipient longevity matching. However, estimated wait-time to deceased donor transplantation is difficult to predict post-KAS. METHODS: Using the Kidney-Pancreas Simulated Allocation Model software (KPSAM), a program that the Organ Procurement and Transplant Network uses to assess policy proposals, we compared the kidney allocations of both the new (post-KAS) and old policies (pre-KAS) (10 iterations for each group; total N = 204,148) and estimated wait-time based on blood type, duration of dialysis exposure, and calculated panel-reactive antibody (CPRA)...
July 2016: Transplantation Proceedings
Byung-Soo Ko, Stavros Drakos, Abdallah G Kfoury, Denise Hurst, Gregory J Stoddard, Carrie A Willis, Julio C Delgado, Elizabeth H Hammond, Edward M Gilbert, Rami Alharethi, Monica P Revelo, Jose Nativi-Nicolau, Bruce B Reid, Stephen H McKellar, Omar Wever-Pinzon, Dylan V Miller, David D Eckels, James C Fang, Craig H Selzman, Josef Stehlik
BACKGROUND: Immune allosensitization can be triggered by continuous-flow left ventricular assist devices (CF LVAD). However, the effect of this type of allosensitization on post-transplant outcomes remains controversial. This study examined the post-transplant course in a contemporary cohort of patients undergoing transplantation with and without LVAD bridging. METHODS: We included consecutive patients who were considered for cardiac transplant from 2006 to 2015...
August 2016: Journal of Heart and Lung Transplantation
J W In, E Y Roh, S Shin, K U Park, E Y Song
BACKGROUND: Calculated panel reactive antibody (cPRA) (%) is percentage of donors that would be incompatible with the candidate, based on the candidate's unacceptable HLA antigens. cPRA based on antigen frequencies of HLA-A, B, and DR has been used in Korea. We developed new cPRA including HLA-Cw, DR51/52/53, and DQ. Changes in new-cPRA were evaluated. METHODS: We analyzed the differences between cPRA based on HLA-A, -B, and -DR antigens (old-cPRA) from cPRA based on HLA-A, -B, -Cw, -DR, -DR51/52/53, and -DQ antigens (new-cPRA) on 125 waitlisted candidates for renal transplantation in Seoul National University Hospital...
April 2016: Transplantation Proceedings
Julie M Yabu, Janet C Siebert, Holden T Maecker
BACKGROUND: Kidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response and to guide therapy. Our objective was to determine whether differences in immune and gene profiles may help identify which candidates will respond to desensitization therapy...
2016: PloS One
Lee Ann Baxter-Lowe, Anna Kucheryavaya, Dolly Tyan, Nancy Reinsmoen
In 2009 calculated panel reactive antibody (CPRA) replaced PRA as the metric for HLA sensitization in the US kidney allocation system. During the next four years, registrants with at least one unacceptable antigen increased (34-40%) and registrants with ≥98% PRA/CPRA increased from 7% to 9% of the waitlist. These changes were accompanied by a reduction in kidney offers refused for positive crossmatch: 14,137 (1.7%) in 2009 and 3,310 in 2013 (0.4%). Registrants with ≥98% PRA/CPRA had highest rates of refusal but also showed substantial improvement (20% in 2009 vs 8% in 2013)...
May 2016: Human Immunology
Douglas S Keith, Gayle M Vranic
For patients with ESRD, kidney transplant offers significant survival and quality-of-life advantages compared with dialysis. But for patients seeking transplant who are highly sensitized, wait times have traditionally been long and options limited. The approach to the highly sensitized candidate for kidney transplant has changed substantially over time owing to new advances in desensitization, options for paired donor exchange (PDE), and changes to the deceased-donor allocation system. Initial evaluation should focus on determining living-donor availability because a compatible living donor is always the best option...
April 7, 2016: Clinical Journal of the American Society of Nephrology: CJASN
Howard M Gebel, Bertram L Kasiske, Sally K Gustafson, Joshua Pyke, Eugene Shteyn, Ajay K Israni, Robert A Bray, Jon J Snyder, John J Friedewald, Dorry L Segev
BACKGROUND AND OBJECTIVES: In December of 2014, the Organ Procurement and Transplant Network implemented a new Kidney Allocation System (KAS) for deceased donor transplant, with increased priority for highly sensitized candidates (calculated panel-reactive antibody [cPRA] >99%). We used a modified version of the new KAS to address issues of access and equity for these candidates. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a simulation, 10,988 deceased donor kidneys transplanted into waitlisted recipients in 2010 were instead allocated to candidates with cPRA≥80% (n=18,004)...
March 7, 2016: Clinical Journal of the American Society of Nephrology: CJASN
M A Mujtaba, W J Komocsar, E Nantz, M D Samaniego, S L Henson, J A Hague, A L Lobashevsky, N G Higgins, M Czader, B K Book, M D Anderson, M D Pescovitz, T E Taber
B cell-activation factor (BAFF) is critical for B cell maturation. Inhibition of BAFF represents an appealing target for desensitization of sensitized end-stage renal disease (ESRD) patients. We conducted a Phase 2a, single-arm, open-label exploratory study investigating the effect of tabalumab (BAFF inhibitor) in patients with ESRD and calculated panel reactive antibodies (cPRAs) >50%. The treatment period duration was 24 weeks. Eighteen patients received tabalumab, at doses of 240-mg subcutaneous (SC) at Week 0 followed by 120-mg SC monthly for 5 additional months...
April 2016: American Journal of Transplantation
K J Tinckam, R Liwski, D Pochinco, M Mousseau, A Grattan, P Nickerson, P Campbell
A calculated panel reactive antibody (cPRA) estimates the percentage of donors with unacceptable antigens (UA) for a recipient. cPRA may be underestimated in transplant candidates with UA to DQA, DPA, and DPB if these are not included in the calculation program. To serve the National Canadian Transplant Programs, a cPRA calculator was developed with complete molecular typing for all donors at HLA-A, B, C, DRB1, DRB3/4/5, DQA1, DQB1, DPA1, and DPB1, all resolved to serologic equivalents. The prevalence of UA at DQA, DPA and DPB was evaluated in a sensitized regional population...
December 2015: American Journal of Transplantation
Patrick Duhamel, Caroline Suberbielle, Philippe Grimbert, Thomas Leclerc, Christian Jacquelinet, Benoit Audry, Laurent Bargues, Dominique Charron, Eric Bey, Laurent Lantieri, Mikael Hivelin
Extensively burned patients receive iterative blood transfusions and skin allografts that often lead to HLA sensitization, and potentially impede access to vascularized composite allotransplantation (VCA). In this retrospective, single-center study, anti-HLA sensitization was measured by single-antigen-flow bead analysis in patients with deep, second- and third-degree burns over ≥40% total body surface area (TBSA). Association of HLA sensitization with blood transfusions, skin allografts, and pregnancies was analyzed by bivariate analysis...
May 2015: Transplant International: Official Journal of the European Society for Organ Transplantation
J Fan, P Tryphonopoulos, A Tekin, S Nishida, G Selvaggi, A Amador, J Jebrock, D Weppler, D Levi, R Vianna, P Ruiz, A Tzakis
The presence of elevated calculated panel reactive antibody (cPRA) and anti-HLA donor specific antibodies (DSA) are high risk factors for acute antibody-mediated rejection (AAMR) in intestinal transplantation that may lead to graft loss. Eculizumab has been used for the treatment of AAMR in kidney transplantation of sensitized patients that do not respond to other treatment. Here, we report a case where eculizumab was used to treat AAMR in a desensitization-resistant intestinal re-transplant patient. A male patient lost his intestinal graft to AAMR 8...
July 2015: American Journal of Transplantation
Edward H Cole, Peter Nickerson, Patricia Campbell, Kathy Yetzer, Nick Lahaie, Jeffery Zaltzman, John S Gill
BACKGROUND: Establishment of a national kidney paired donation (KPD) program represents a unique achievement in Canada's provincially organized health care system. METHODS: Key factors enabling program implementation included consultation with international experts, formation of a unique organization with a mandate to facilitate interprovincial collaboration, and the volunteer efforts of members of the Canadian transplant community to overcome a variety of logistical barriers...
May 2015: Transplantation
Nancy L Reinsmoen
The implementation of the solid phase antibody assays has allowed for the detection and characterization of human leukocyte antigen (HLA) specific antibodies with greater sensitivity and specificity. This information can then be used along with the donor's HLA typing to predict crossmatch results (a virtual crossmatch). Using these data and the level of immunological risk assessed to the antibodies detected, the determination of unacceptable antigens can be made. The calculated panel reactive antibody (CPRA) provides for a means to determine the frequency of these unacceptable antigens in the donor population and thereby predict the probability of a positive crossmatch...
2013: Clinical Transplants
Ajay K Israni, Nicholas Salkowski, Sally Gustafson, Jon J Snyder, John J Friedewald, Richard N Formica, Xinyue Wang, Eugene Shteyn, Wida Cherikh, Darren Stewart, Ciara J Samana, Adrine Chung, Allyson Hart, Bertram L Kasiske
In 2013, the Organ Procurement and Transplantation Network in the United States approved a new national deceased donor kidney allocation policy that introduces the kidney donor profile index (KDPI), which gives scores of 0%-100% based on 10 donor factors. Kidneys with lower KDPI scores are associated with better post-transplant survival. Important features of the new policy include first allocating kidneys from donors with a KDPI≤20% to candidates in the top 20th percentile of estimated post-transplant survival, adding waiting time from dialysis initiation, conferring priority points for a calculated panel-reactive antibody (CPRA)>19%, broader sharing of kidneys for candidates with a CPRA≥99%, broader sharing of kidneys from donors with a KDPI>85%, eliminating the payback system, and allocating blood type A2 and A2B kidneys to blood type B candidates...
August 2014: Journal of the American Society of Nephrology: JASN
Min Luo, Lixin Yu, Lulu Xiao
OBJECTIVE: To establish a calculated panel reactive antibody (CPRA) method to analyze the donor-recipient incompatibility rate in PRA-positive kidney recipients and estimate the probability of these recipients to receive kidney transplantation. METHODS: Based on the database of HLA-A, -B, -DR genes and A-B, A-DR, B-DR, A-B-DR haplotype frequencies collected from 2004 donors from Jan 2000 to Dec 2012, we analyzed CPRA in 202 PRA-positive recipients and evaluated the consistency between PRA and CPRA assessments using a CPRA-Java calculator software, which returned a percentage of CPRA (representing the probability of unacceptable HLA in the donor group) after input of HLA-specific antibodies of a PRA-positive recipient...
April 2014: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Kelley M K Haarberg, Anat R Tambur
INTRODUCTION: Precise and timely detection of human leukocyte antigen (HLA) donor-specific antibodies (DSAs) is vital for evaluating humoral immune status of patients pre- and post-transplantation. SOURCE OF DATA: Clinically relevant articles on theory, development, methodology and application of HLA-DSA testing in kidney transplantation. AREAS OF AGREEMENT AND CONTROVERSY: The availability of solid phase HLA-antibody testing revolutionized our ability to detect HLA-DSA and to appreciate their significance in kidney transplant outcome...
June 2014: British Medical Bulletin
L D Snyder, A L Gray, J M Reynolds, G M Arepally, A Bedoya, M G Hartwig, R D Davis, K E Lopes, W E Wegner, D F Chen, S M Palmer
As HLAs antibody detection technology has evolved, there is now detailed HLA antibody information available on prospective transplant recipients. Determining single antigen antibody specificity allows for a calculated panel reactive antibodies (cPRA) value, providing an estimate of the effective donor pool. For broadly sensitized lung transplant candidates (cPRA ≥ 80%), our center adopted a pretransplant multi-modal desensitization protocol in an effort to decrease the cPRA and expand the donor pool. This desensitization protocol included plasmapheresis, solumedrol, bortezomib and rituximab given in combination over 19 days followed by intravenous immunoglobulin...
April 2014: American Journal of Transplantation
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