Long-Term Improvement of Graft Survival in Cadaveric Renal Retransplantation by Flow Cytometric Crossmatching

Bryan, Christopher; Baier, K. A.; Nelson, Paul W.; Luger, Alan M.; Martinez, John; Pierce, G. E.; Ross, Gilbert; Shield, Charles F.; Warady, Bradley A.; Aeder, Mark I.; Helling, Thomas S.

doi:10.1097/00007890-199805131-00454

Cited by 20 publications

(35 citation statements)

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“…Short-term graft survival steadily improved at a comparable level among all induction categories including no-induction therapy over the past decade. These findings raise the following important issues: (1) clinical utility of induction therapy in LRT in the setting of TAC/MPA maintenance immunosuppression (9,16), and (2) improved outcomes that may be accounted for by other factors, such as sensitive HLA antibody detection (17)(18)(19), more sensitive cross-match techniques (20,21), implementation of virtual cross-match in 2006 (22,23), and utilization of a calculated PRA system in 2009 into a routine allocation system (19). A large sample size (a patient population ranging from 1600 to 7000) needed to detect small differences in observed outcomes among induction types is most likely prohibitive to prospective randomized trials (10).…”

Section: Discussionmentioning

confidence: 99%

Induction Therapies in Live Donor Kidney Transplantation on Tacrolimus and Mycophenolate With or Without Steroid Maintenance

Tanrıöver¹,

Zhang²,

MacConmara

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first line agent in living donor renal transplantation (LRT). However, use of IL2-RA remains controversial in LRT with tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids.Design, setting, participants, & measurements The Organ Procurement and Transplantation Network registry was studied for patients receiving LRT from 2000 to 2012 maintained on TAC/MPA at discharge (n536,153) to compare effectiveness of IL2-RA to other induction options. The cohort was initially divided into two groups based on use of maintenance steroid at time of hospital discharge: steroid (n525,996) versus no-steroid (n510,157). Each group was further stratified into three categories according to commonly used antibody induction approach: IL2-RA, rabbit anti-thymocyte globulin (r-ATG), and no-induction in the steroid group versus IL2-RA, r-ATG and alemtuzumab in the no-steroid group. The main outcomes were the risk of acute rejection at 1 year and overall allograft failure (graft failure or death) post-transplantation through the end of follow-up. Propensity score-weighted regression analysis was used to minimize selection bias due to non-random assignment of induction therapies.Results Multivariable logistic and Cox analysis adjusted for propensity score showed that outcomes in the steroid group were similar between no-induction (odds ratio [OR], 0.96; 95% confidence interval [95% CI], 0.86 to 1.08 for acute rejection; and hazard ratio [HR], 0.99; 95% CI, 0.90 to 1.08 for overall allograft failure) and IL2-RA categories. In the no-steroid group, odds of acute rejection with r-ATG (OR, 0.73; 95% CI, 0.59 to 0.90) and alemtuzumab (OR, 0.53; 95% CI, 0.42 to 0.67) were lower; however, overall allograft failure risk was higher with alemtuzumab (HR, 1.27; 95% CI, 1.03 to 1.56) but not with r-ATG (HR, 1.19; 95% CI, 0.97 to 1.45), compared with IL2-RA induction.Conclusions Compared with no-induction therapy, IL2-RA induction was not associated with better outcomes when TAC/MPA/steroids were used in LRT recipients. r-ATG appears to be an acceptable and possibly the preferred induction alternative for IL2-RA in steroid-avoidance protocols.

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Section: Discussionmentioning

confidence: 99%

Induction Therapies in Live Donor Kidney Transplantation on Tacrolimus and Mycophenolate With or Without Steroid Maintenance

Tanrıöver¹,

Zhang²,

MacConmara

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…Studies using CDC techniques have reported allosensitization rates of approximately 30% in high-risk recipients, in contrast to the approximately 50% rate that we observed with FlowPRA screening (29 -31). These anti-HLA antibodies detected solely by flow cytometry are clinically relevant and have been increasingly associated with adverse outcomes posttransplantation (12)(13)(14)(31)(32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

Leukocyte Reduction of Red Blood Cell Transfusions Does not Decrease Allosensitization Rates in Potential Kidney Transplant Candidates

Karpinski¹,

Pochinco²,

Dembinski³

et al. 2004

Journal of the American Society of Nephrology

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Abstract. A significant proportion of potential kidney transplant candidates continue to periodically require blood transfusions that carry a risk of allosensitization. Leukocyte reduction (leukoreduction) of blood products has been proved to reduce transfusion-associated allosensitization in patients with hematologic malignancies; however, the effect in potential kidney transplant candidates is unknown. A total of 112 kidney transplant candidates who received red blood cell transfusions while on the transplant waiting list were identified retrospectively. Sixty received a transfusion before leukoreduction (non-LR), and 52 received a transfusion after the local implementation of universal leukoreduction of blood products (LR). There was no difference in transfusion-associated allosensitization rates in patients who received a transfusion during the two eras (non-LR 27% [16 of 60] versus LR 33% [17/52]; NS). Likewise, no difference was observed in subgroups identified as being at high risk of allosensitization (previous pregnancy, transplant, or five or more previous transfusions) or at low risk (no previous allogeneic exposures) (high risk: non-LR 52% versus LR 55%; low risk: non-LR 10% versus LR 8%). Multivariate analysis revealed previous pregnancy to be the only significant risk factor associated with transfusion-associated allosensitization (relative risk, 8.2; 95% confidence interval, 2.4 to 24.0; P ϭ 0.0001). Leukoreduction, in particular, was not associated with any protective effect. In summary, leukoreduction of red blood cell transfusions does not confer any protection against transfusion-associated allosensitization for potential kidney transplant candidates. Physicians who care for patients with ESRD must continue to practice careful transfusion avoidance while alternative strategies to minimize transfusion associated allosensitization are sought.Despite the fact that recombinant erythropoietins have substantially decreased the need for transfusions in patients with ESRD, United Network for Organ Sharing (UNOS) data indicate that approximately 30% of wait-listed transplant candidates continue to receive red blood cell (RBC) transfusions at some point before transplantation (1, 2). In the past, some transplant programs administered deliberate pretransplant transfusions aimed at optimizing graft outcomes (i.e., the beneficial transfusion effect); however, more recent data indicate that this beneficial effect is no longer apparent, perhaps as a result of improving graft outcomes overall (2-5). Concerns of transfusion-associated allosensitization persist for potential transplant candidates, and it is likely that the majority of current transfusions are administered for other clinical indications.

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“…2 Evolution to flow cytometry cross-matching (FCXM) offers improved sensitivity for low titer but nonetheless, pathogenic antibodies. [3][4][5][6][7][8][9] Newer immunoassays (using ELISA plates or microsphere technology), where purified HLA antigens are covalently bound to a solid-phase platform, have further improved sensitivity and specificity of HLA antibody detection. 10 Despite advancements in technology, newer solid-phase assays have a number of interpretive considerations that must be appreciated by clinicians in order to more appropriately apply test results to patient care.…”

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confidence: 99%

Utility of HLA Antibody Testing in Kidney Transplantation

Konvalinka¹,

Tinckam

2015

Journal of the American Society of Nephrology

163

135

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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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Long-Term Improvement of Graft Survival in Cadaveric Renal Retransplantation by Flow Cytometric Crossmatching

Cited by 20 publications

References 0 publications

Induction Therapies in Live Donor Kidney Transplantation on Tacrolimus and Mycophenolate With or Without Steroid Maintenance

Induction Therapies in Live Donor Kidney Transplantation on Tacrolimus and Mycophenolate With or Without Steroid Maintenance

Leukocyte Reduction of Red Blood Cell Transfusions Does not Decrease Allosensitization Rates in Potential Kidney Transplant Candidates

Utility of HLA Antibody Testing in Kidney Transplantation

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