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Pretransplant Kinetics of Anti-HLA Antibodies in Patients on the Waiting List for Kidney Transplantation.

ABSTRACT: BACKGROUND:Patients on organ transplant waiting lists are evaluated for preexisting alloimmunity to minimize episodes of acute and chronic rejection by regularly monitoring for changes in alloimmune status. There are few studies on how alloimmunity changes over time in patients on kidney allograft waiting lists, and an apparent lack of research-based evidence supporting currently used monitoring intervals. METHODS:To investigate the dynamics of alloimmune responses directed at HLA antigens, we retrospectively evaluated data on anti-HLA antibodies measured by the single-antigen bead assay from 627 waitlisted patients who subsequently received a kidney transplant at University Hospital Zurich, Switzerland, between 2008 and 2017. Our analysis focused on a filtered dataset comprising 467 patients who had at least two assay measurements. RESULTS:Within the filtered dataset, we analyzed potential changes in mean fluorescence intensity values (reflecting bound anti-HLA antibodies) between consecutive measurements for individual patients in relation to the time interval between measurements. Using multiple approaches, we found no correlation between these two factors. However, when we stratified the dataset on the basis of documented previous immunizing events (transplant, pregnancy, or transfusion), we found significant differences in the magnitude of change in alloimmune status, especially among patients with a previous transplant versus patients without such a history. Further efforts to cluster patients according to statistical properties related to alloimmune status kinetics were unsuccessful, indicating considerable complexity in individual variability. CONCLUSIONS:Alloimmune kinetics in patients on a kidney transplant waiting list do not appear to be related to the interval between measurements, but are instead associated with alloimmunization history. This suggests that an individualized strategy for alloimmune status monitoring may be preferable to currently used intervals.

SUBMITTER: Togninalli M

PROVIDER: S-EPMC6830788 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Pretransplant Kinetics of Anti-HLA Antibodies in Patients on the Waiting List for Kidney Transplantation.

Togninalli Matteo M Yoneoka Daisuke D Kolios Antonios G A AGA Borgwardt Karsten K Nilsson Jakob J

Journal of the American Society of Nephrology : JASN 20191025 11

<h4>Background</h4>Patients on organ transplant waiting lists are evaluated for preexisting alloimmunity to minimize episodes of acute and chronic rejection by regularly monitoring for changes in alloimmune status. There are few studies on how alloimmunity changes over time in patients on kidney allograft waiting lists, and an apparent lack of research-based evidence supporting currently used monitoring intervals.<h4>Methods</h4>To investigate the dynamics of alloimmune responses directed at HLA ...[more]

PMID: 31653784

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Project description:ImportanceWhile recent policy reforms aim to improve access to kidney transplantation for patients with end-stage kidney disease, the cost implications of kidney waiting list expansion are not well understood. The Organ Acquisition Cost Center (OACC) is the mechanism by which Medicare reimburses kidney transplantation programs, at cost, for costs attributable to kidney transplantation evaluation and waiting list management, but these costs have not been well described to date.ObjectivesTo describe temporal trends in mean OACC costs per kidney transplantation and to identify factors most associated with cost.Design, setting, and participantsThis economic evaluation included all kidney transplantation waiting list candidates and recipients in the United States from 2012 to 2017. A population-based study of cost center reports was conducted using data from all Center of Medicare & Medicaid-certified transplantation hospitals. Data analysis was conducted from June to August 2021.ExposuresYear, local price index, transplantation and waiting list volume of transplantation program, and comorbidity burden.Main outcomes and measuresMean OACC costs per kidney transplantation.ResultsIn 1335 hospital-years from 2012 through 2017, Medicare's share of OACC costs increased from $0.95 billion in 2012 to $1.32 billion in 2017 (3.7% of total Medicare End-Stage Renal Disease program expenditure). Median (IQR) OACC costs per transplantation increased from $81 000 ($66 000 to $103 000) in 2012 to $100 000 ($82 000 to $125 000) in 2017. Kidney organ procurement costs contributed to 36% of mean OACC costs per transplantation throughout the study period. During the study period, transplantation hospitals experienced increases in kidney waiting list volume, kidney waiting list active volume, kidney transplantation volume, and comorbidity burden. For a median-sized transplantation program, mean OACC costs per transplantation decreased with more transplants (-$3500 [95% CI, -$4300 to -$2700] per 10 transplants; P < .001) and increased with year ($4400 [95% CI, $3500 to $5300] per year; P < .001), local price index ($1900 [95% CI, $200 to $3700] per 10-point increase; P = .03), patients listed active on the waiting list ($3100 [95% CI, $1700 to $4600] per 100 patients; P < .001), and patients on the waiting list with high comorbidities ($1500 [9% CI, $600 to $2500] per 1% increase in proportion of waitlisted patients with the highest comorbidity score; P = .002).Conclusions and relevanceIn this study, OACC costs increased at 4% per year from 2012 to 2017 and were not solely attributable to the cost of organ procurement. Expanding the waiting list will likely contribute to further increases in the mean OACC costs per transplantation and substantially increase Medicare liability.

Project description:Due to the current organ shortage, living donor kidney transplantation is increasingly performed across HLA (human leukocyte antigen) or ABO antibody barriers. There is still uncertainty about the risk of antibody-mediated rejection (AMR) episodes, which may limit long-term graft survival. From March 2007 to December 2016, 58 sensitized living donor kidney transplant candidates were identified and 38 patients eventually included in the study: 36 patients (95%) had pre-transplant and pre-desensitization Luminex-detected donor-specific HLA antibodies (DSA), and 17/36 patients (47%) in addition had a positive crossmatch result. Two patients had no detectable DSA but a positive CDC B-cell crossmatch result. Patients were treated with pre- and post-transplant apheresis and powerful immunosuppression including the anti-CD20 antibody rituximab (N = 36) in combination with thymoglobulin (N = 20) or anti-IL2 receptor antibody (N = 18). The results of the 38 successfully desensitized and transplanted patients were retrospectively compared to the results of 76 matched standard-risk recipients. Desensitized patients showed patient and graft survival rates similar to that of standard-risk recipients (P = 0.55 and P = 0.16, respectively). There was a trend toward reduced death-censored graft survival in desensitized patients (P = 0.053) which, however, disappeared when the 34 patients who were transplanted after introduction of sensitive Luminex testing were analyzed (P = 0.43). The incidence of rejection episodes without borderline changes were in desensitized patients with 21% similar to the 18% in standard-risk patients (P = 0.74). Thirty-six patients had pre-transplant HLA class I and/or II DSA that were reduced by 85 and 81%, respectively, during pre-transplant desensitization (P < 0.001 for both). On day 360 after transplantation, 20 of 36 (56%) patients had lost their DSA. The overall AMR rate was 6% in these patients, but as high as 60% in 5 (14%) patients with persistent and de novo DSA during year 1; 2 (40%) of whom lost their graft due to AMR. Eleven (31%) patients with persistent DSA but without de novo DSA had an AMR rate of 18% without graft loss while one patient lost her graft without signs of AMR. Our desensitization protocol for pre-sensitized living donor kidney transplant recipients with DSA resulted in good graft outcomes with side effects and rejection rates similar to that of standard-risk recipients. Adequate patient selection prior to transplantation and frequent immunological monitoring thereafter is critical to minimize rejection episodes and subsequent graft loss.

Dataset Information

Pretransplant Kinetics of Anti-HLA Antibodies in Patients on the Waiting List for Kidney Transplantation.

Publications

Pretransplant Kinetics of Anti-HLA Antibodies in Patients on the Waiting List for Kidney Transplantation.

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