Donor-Specific Antibody Levels and Three Generations of Crossmatches to Predict Antibody-Mediated Rejection in Kidney Transplantation

Riethmüller, Sebastian; Ferrari‐Lacraz, Sylvie; Müller, Markus K.; Raptis, Dimitri Aristotle; Hadaya, Karine; Rüsi, Barbara; Laube, Guido F.; Schneiter, Gregory; Fehr, Thomas; Villard, Jean

doi:10.1097/tp.0b013e3181e36e08

Cited by 87 publications

(70 citation statements)

References 42 publications

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“…47,86,87 DSA with a Negative XM: Defining Risk Remains Challenging The increased sensitivity of SAB allows DSA to be detected even with a negative XM. 80,88,89 AMR rates of 20%-55% are reported under these circumstances, 22,23,83,88,90,91 with AMR negatively affecting the impact of DSA on graft survival in some studies 90 but not all. 83 In series where DSA are associated with worse allograft survival, 82,83,88,[92][93][94][95] DSA MFI is an imperfect discriminator of outcomes.…”

Section: Utility Of Hla Antibody Testing Pretransplantmentioning

confidence: 99%

Utility of HLA Antibody Testing in Kidney Transplantation

Konvalinka¹,

Tinckam

2015

Journal of the American Society of Nephrology

157

131

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HLA antigens are polymorphic proteins expressed on donor kidney allograft endothelium and are critical targets for recipient immune recognition. HLA antibodies are risk factors for acute and chronic rejection and allograft loss. Solid-phase immunoassays for HLA antibody detection represent a major advance in sensitivity and specificity over cell-based methods and are widely used in organ allocation and pretransplant risk assessment. Post-transplant, development of de novo donorspecific HLA antibodies and/or increase in donor-specific antibodies from pretransplant levels are associated with adverse outcomes. Although single antigen bead assays have allowed sensitive detection of recipient HLA antibodies and their specificities, a number of interpretive considerations must be appreciated to understand test results in clinical and research contexts. This review, which is especially relevant for clinicians caring for transplant patients, discusses the technical aspects of single antigen bead assays, emphasizes their quantitative limitations, and explores the utility of HLA antibody testing in identifying and managing important pre-and post-transplant clinical outcomes.

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Section: Utility Of Hla Antibody Testing Pretransplantmentioning

confidence: 99%

Utility of HLA Antibody Testing in Kidney Transplantation

Konvalinka¹,

Tinckam

2015

Journal of the American Society of Nephrology

157

131

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“…The presence of circulating donor-specific human leukocyte antigen antibodies (HLA-DSA) and complement factor C4d accumulation in the graft has been associated with CAMR. Techniques for the detection of HLA antibodies (HLAab) have become more sensitive with the introduction of solid phase assays, such as the enzyme-linked immunosorbent assay (ELISA) and Luminex assay [7,8]. Although there have been several studies showing that the presence of HLA-DSA after transplantation is associated with chronic graft failure [9][10][11][12], many adult patients with circulating HLA-DSA and stable graft function have also been described [10,13,14], and the clinical relevance of HLAab has been questioned [12,[15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Donor-specific HLA antibodies and graft function in children after renal transplantation

et al. 2012

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“…The rejection rate was 73% in patients with MFI values Ͼ2000 and 12.5% in patients with MFI values Ͻ2000. Riethmuller et al transplanted 20 CDC cross-match-negative patients without any desensitization treatment and retrospectively identified DSAs by Luminex after transplantation (61). AMR and cellular rejection rate were 35% and 40%, respectively, and the specificity of MFI values Ͼ5200 in prediction of AMR was 100%.…”

Section: Current Problems In Desensitization Protocolsmentioning

confidence: 99%

Desensitization Protocols and Their Outcome

Marfo

Ling

et al. 2011

Clinical Journal of the American Society of Nephrology

229

182

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SummaryIn the last decade, transplantation across previously incompatible barriers has increasingly become popular because of organ donor shortage, availability of better methods of detecting and characterizing anti-HLA antibodies, ease of diagnosis, better understanding of antibody-mediated rejection, and the availability of effective regimens. This review summarizes all manuscripts published since the first publication in 2000 on desensitized patients and discusses clinical outcomes including acute and chronic antibody-mediated rejection rate, the new agents available, kidney paired exchange programs, and the future directions in sensitized patients. There were 21 studies published between 2000 and 2010, involving 725 patients with donor-specific anti-HLA antibodies (DSAs) who underwent kidney transplantation with different desensitization protocols. All studies were single center and retrospective. The patient and graft survival were 95% and 86%, respectively, at a 2-year median follow-up. Despite acceptable short-term patient and graft survivals, acute rejection rate was 36% and acute antibody-mediated rejection rate was 28%, which is significantly higher than in nonsensitized patients. Recent studies with longer follow-up of those patients raised concerns about long-term success of desensitization protocols. The studies utilizing protocol biopsies in desensitized patients also reported higher subclinical and chronic antibody-mediated rejection. An association between the strength of DSAs determined by median fluorescence intensity values of Luminex single-antigen beads and risk of rejection was observed. Two new agents, bortezomib, a proteasome inhibitor, and eculizumab, an anti-complement C5 antibody, were recently introduced to desensitization protocols. An alternative intervention is kidney paired exchange, which should be considered first for sensitized patients.

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Donor-Specific Antibody Levels and Three Generations of Crossmatches to Predict Antibody-Mediated Rejection in Kidney Transplantation

Abstract: In sensitized recipients, the best prediction of AMR and consecutively reduced graft function is delivered by DSA-I alone at high strength or by DSA-I at low strength in combination with the LXM or CXM.

Cited by 87 publications

References 42 publications

Utility of HLA Antibody Testing in Kidney Transplantation

Utility of HLA Antibody Testing in Kidney Transplantation

Donor-specific HLA antibodies and graft function in children after renal transplantation

Desensitization Protocols and Their Outcome

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