Extremely High Association Between Appearance of HLA Antibodies and Failure of Kidney Grafts in a Five-Year Longitudinal Study

Mao, Quanzong; Terasaki, Paul I.; Cai, Junchao; Briley, Kimberly P.; Catrou, Paul G.; Haisch, Carl E.; Rebellato, Lorita M.

doi:10.1111/j.1600-6143.2006.01711.x

Cited by 200 publications

(131 citation statements)

References 16 publications

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“…In the present study we also analyzed the development of HLA alloantibodies and DSA, which are increasingly recognized as a major risk factor for kidney transplant failure and are associated with 40% lower graft survival after 10 years [26,27]. The frequency of de-novo DSA observed in our study is within the 15-25% range reported in kidney transplantation [28,29].…”

Section: Discussionsupporting

confidence: 53%

Deceased Donor Kidney Transplantation in the Eurotransplant Senior Program (ESP): A Single-Center Experience from 2008 to 2013

et al. 2016

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Background:The aim of this study was to evaluate the outcome after transplantation of deceased allografts in donor/recipient pairs aged ³65 years enrolled in the Eurotransplant Senior Program (ESP). Material/Methods:In this retrospective cohort study we evaluated data from 89 patients transplanted under the ESP protocol from 2008 to 2013. Outcome parameters included graft and patient survival, rate of biopsy-proven acute rejections (BPAR), peri-and post-operative complications, tumor development, development of donor-specific antibodies (DSA), and the prognostic role of preimplantation biopsies. Results:One-year patient and allograft survival rates were 92.1% and 84.3%, respectively. During follow-up, 23 (26%) patients died; the major cause of death was sepsis, followed by cardiovascular events and malignancies. BPAR episodes were frequent within the first year (~33%) and overall were less common in patients treated with tacrolimus. Post-transplant malignancies were seen in 15 (17%) patients. During follow-up, 16 (18%) patients developed DSA; patients with delayed graft function (DGF) were more likely to develop DSA (p=0.029). A higher preimplantation biopsy score was associated with DGF but did not predict later graft outcome. Conclusions:The results highlight increased risks in ESP transplant candidates and the importance of careful surveillance of this patient group.

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Section: Discussionsupporting

confidence: 53%

Deceased Donor Kidney Transplantation in the Eurotransplant Senior Program (ESP): A Single-Center Experience from 2008 to 2013

et al. 2016

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“…However, alemtuzumab treatment was associated with an increased risk for the development of donorspecific anti-HLA Abs (DSA) and with an excess risk for early Ab-mediated rejection, particularly in a calcineurin inhibitor-free immunosuppressive regimen (3)(4)(5). The above data converge to suggest that, in the clinical setting of minimal maintenance immunosuppression, alemtuzumab-induced lymphocyte depletion might result in activation of the humoral response toward alloantigens.…”

mentioning

confidence: 63%

In Kidney Transplant Patients, Alemtuzumab but Not Basiliximab/Low-Dose Rabbit Anti-Thymocyte Globulin Induces B Cell Depletion and Regeneration, Which Associates with a High Incidence of De Novo Donor-Specific Anti-HLA Antibody Development

Todeschini

Cortinovis

Perico

et al. 2013

The Journal of Immunology

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In this single-center matched-cohort study, we evaluated the phenotype of repopulating B cells and its correlation with donor-specific anti-HLA Ab development and long-term graft function in 16 renal transplant recipients and 32 age- and gender-matched controls induced with alemtuzumab or basiliximab (Bas)/low-dose rabbit anti-thymocyte globulin (rATG), respectively. Alemtuzumab, but not Bas/rATG, profoundly depleted peripheral B cells in the first 2 mo posttransplantation. Early posttransplant, naive B cells were significantly depleted, whereas Ag-experienced and memory B cells were partially spared. Transitional B cells transiently increased 2 mo posttransplant. At month 6 posttransplant, pregerminal center B cells emerged, a process promoted by increased BAFF serum levels. Thereafter, B cell counts increased progressively, mainly due to expansion of naive B cells. Conversely, Bas/rATG did not modify the B cell phenotype throughout the follow-up period. Alemtuzumab was associated with a higher incidence of de novo DSA compared with Bas/rATG. DSA development was predicted by changes in the B cell compartment and correlated with worse long-term graft function. Thus, alemtuzumab-induced B cell depletion/reconstitution may promote chronic humoral responses against the graft.

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“…HLA antibodies in general and donor-specific HLA antibodies (DSA) in particular are significant risk factors for graft survival after renal transplantation (1)(2)(3)(4). HLA antibodies may cause antibody-mediated rejection (AMR) which is associated with poor prognosis (5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Donor-Specific HLA Antibodies in a Cohort Comparing Everolimus With Cyclosporine After Kidney Transplantation

Liefeldt

Brakemeier

Glander

et al. 2012

American Journal of Transplantation

228

175

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Donor-specific HLA antibodies (DSA) have a negative impact on kidney graft survival. Therefore, we analyzed the occurrence of DSA and antibody-mediated rejection (AMR) in patients from two prospective randomized trials in our center. At 3-4.5 months posttransplant 127 patients were randomized to continue cyclosporine or converted to everolimus therapy. The presence of DSA was prospectively assessed using Luminex assays. AMR was defined according to the Banff 2009 classification. Antibody screening was available in 126 patients with a median follow-up of 1059 days. Seven out of 65 (10.8%) patients on cyclosporine developed DSA after a median of 991 days. In comparison, 14/61 patients (23.0%) randomized to everolimus developed DSA after 551 days (log-rank: p = 0.048). Eight patients on everolimus compared to two patients on cyclosporine developed AMR (log-rank: p = 0.036). Four of 10 patients with AMR-all in the everolimus group-lost their graft. A multivariate regression model revealed everolimus, >3 mismatches and living donor as significant risk factors for DSA. Acute rejection within the first year, >3 mismatches, everolimus and living donor were independent risk factors for AMR. This single center analysis demonstrates for the first time that everolimus-based immunosuppression is associated with an increased risk for the development of DSA and AMR.

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Extremely High Association Between Appearance of HLA Antibodies and Failure of Kidney Grafts in a Five-Year Longitudinal Study

Cited by 200 publications

References 16 publications

Deceased Donor Kidney Transplantation in the Eurotransplant Senior Program (ESP): A Single-Center Experience from 2008 to 2013

Deceased Donor Kidney Transplantation in the Eurotransplant Senior Program (ESP): A Single-Center Experience from 2008 to 2013

In Kidney Transplant Patients, Alemtuzumab but Not Basiliximab/Low-Dose Rabbit Anti-Thymocyte Globulin Induces B Cell Depletion and Regeneration, Which Associates with a High Incidence of De Novo Donor-Specific Anti-HLA Antibody Development

Donor-Specific HLA Antibodies in a Cohort Comparing Everolimus With Cyclosporine After Kidney Transplantation

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