Dataset Information

Pretransplant IgA-Anti-Beta 2 Glycoprotein I Antibodies As a Predictor of Early Graft Thrombosis after Renal Transplantation in the Clinical Practice: A Multicenter and Prospective Study.

ABSTRACT:

Background

Graft thrombosis is a devastating complication after renal transplantation. We recently described the association of anti-beta-2-glycoprotein-I (IgA-ab2GP1) antibodies with early graft loss mainly caused by thrombosis in a monocenter study.

Methods

Multicenter prospective observational cohort study.

Setting and participants

Seven hundred forty patients from five hospitals of the Spanish Forum Renal Group transplanted from 2000 to 2002 were prospectively followed-up for 10?years.

Outcomes

Early graft loss and graft loss by thrombosis.

Measurements

The presence of IgA anti-B2GP1 antibodies in pretransplant serum was examined using the same methodology in all the patients.

Results

At transplantation, 288 patients were positive for IgA-B2GP1 (39%, Group-1) and the remaining were negative (Group-2). Graft loss at 6?months was higher in Group-1 (12.5 vs. 4.2% p?p?p?p?p?=?0.005).

Limitations

Patients were obtained during a 3-year period (1 January 2000-31 December 2002) and kidneys were only transplanted from brain-dead donors. Nowadays, the patients are older and the percentage of sensitized and retransplants is high.

Conclusion

In a prospective observational multicenter study, we were able to corroborate that pretransplant presence of IgA-aB2GP1 was the main risk factor for graft thrombosis and early graft loss. Therefore, a prospective study is needed to evaluate the efficacy and safety of prophylactic anticoagulation to avoid this severe complication.

SUBMITTER: Morales JM

PROVIDER: S-EPMC5857545 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Pretransplant IgA-Anti-Beta 2 Glycoprotein I Antibodies As a Predictor of Early Graft Thrombosis after Renal Transplantation in the Clinical Practice: A Multicenter and Prospective Study.

Morales Jose M JM Serrano Manuel M Martinez-Flores Jose Angel JA Gainza Fracisco Javier FJ Marcen Roberto R Arias Manuel M Escuin Fernando F Pérez Dolores D Andres Amado A Martínez Miguel Angel MA Maruri Naroa N Alvarez Eva E Castañer José Luis JL López-Hoyos Marcos M Serrano Antonio A

Frontiers in immunology 20180312

<h4>Background</h4>Graft thrombosis is a devastating complication after renal transplantation. We recently described the association of anti-beta-2-glycoprotein-I (IgA-ab2GP1) antibodies with early graft loss mainly caused by thrombosis in a monocenter study.<h4>Methods</h4>Multicenter prospective observational cohort study.<h4>Setting and participants</h4>Seven hundred forty patients from five hospitals of the Spanish Forum Renal Group transplanted from 2000 to 2002 were prospectively followed- ...[more]

PMID: 29593726

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Project description:Background: The presence of anti-Beta 2 glycoprotein antibodies (aB2GP1) of IgA isotype is common in patients with functional impairment of the organs in which B2GP1 is elaborated. Pretransplant IgA aB2GP1 has been associated with increased risk of thrombosis in kidney and heart transplanted patients and has also been related with early mortality after heart transplantation. Circulating immune complexes between IgA and B2GP1 (B2A-CIC) have been described in the blood of patients positive for IgA aB2GP1 with thrombotic clinical symptoms. In kidney transplanted patients, B2A-CIC is a biomarker that predicts which patients IgA aB2GP1 positive are at risk of thrombosis events following kidney transplantation and may lead to early prophylactic treatment. The prevalence of B2A-CIC and its relation with outcomes after heart transplantation is not known. Methods: Follow-up study based on 151 consecutive patients who received a heart transplant. Autoantibodies and B2A-CIC were quantified in pre-transplant serum samples. Three groups of patients were followed-up for 2 years: Group-1, positive for IgA aB2GP1 and B2A-CIC (N = 19). Group-2, only positive for IgA aB2GP1 (N = 28). Group-0 (control group): IgA aB2GP1 negative (N = 104). Results: Kaplan-Meir survival analysis showed that mortality in B2A-CIC positive was higher than group-0 at 3 months (HR:5.08; 95%CI: 1.36-19.01) and at 2 years (HR:3.82; 95%CI: 1.54-12.66). No significant differences were observed between group-2 and group-0. Multivariate analysis identified B2A-CIC as the most important independent risk factor for early mortality (OR = 6.12; 95% CI: 1.93-19.4). Post-transplant incidence of thrombosis was significantly higher in B2A-CIC positive patients than in the control group (OR: 6.42; 95%CI: 2.1-19.63). Multivariate analysis identified the presence of B2A-CIC (OR: 6.13; 95%CI: 2.1-19.63) and the pre-transplant habit of smoking actively (OR: 4.18; 95%CI: 1.35-12.94) as independent risk factor for thrombosis. The proportion of patients who had thrombotic events or died in the first trimester was significantly higher in group-1 (73.7%) than in group-0 (16.3%; p < 0.001) and in group-2 (39.3%; p = 0.02). Multivariate analysis identified B2A-CIC as the main independent risk factor for early outcomes (mortality or thrombosis) in the first 3 months after heart transplant (OR = 11.42, 95% CI: 1.69-9.68). Conclusion: B2A-CIC are a predictor of early mortality and thrombosis after heart transplant.

Project description: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.

Project description:BackgroundCompared to the general population, kidney transplant recipients are at increased risk of hemorrhage and thrombosis. Whether this risk is affected by graft function and albuminuria is unknown.ObjectiveTo determine the association between graft function and albuminuria and the risk of post-transplant hemorrhage and thrombosis.DesignRetrospective cohort study.SettingWe used linked health care databases in Alberta, Canada.Patients/sample/participantsWe included adult kidney transplant recipients from 2002 to 2015 with a functioning graft at 1 year.MeasurementsEstimated glomerular filtration rate (eGFR) and albuminuria measurements at 1 year post-transplant were used to categorize recipients (eGFR: ≥45 vs. <45 mL/min/1.73 m2; albuminuria: absence vs. presence). We determined the rates of post-transplant hemorrhage and venous thrombosis based on validated diagnostic and procedural codes.MethodsWe determined the association between categories of eGFR and albuminuria and post-transplant hemorrhage and venous thrombosis using Poisson regression with log link.ResultsOf 1284 kidney transplant recipients, 21% had an eGFR <45 mL/min/1.73 m2 and 40% had presence of albuminuria at 1 year post-transplant. Over a median follow-up of 6 years, there were 100 hemorrhages (12.6 events per 1000 person-years) and 57 venous thrombosis events (7.1 events per 1000 person-years). The age- and sex-adjusted rate of hemorrhage and thrombosis was over 2-fold higher in recipients with lower eGFR and presence of albuminuria compared to higher eGFR and no albuminuria (hemorrhage: incidence rate ratio, IRR, 2.6, 95% confidence interval [CI]: 1.5-4.4, P = .001; thrombosis: IRR, 2.3, 95% CI: 1.1-5.0, P = .046).LimitationsComplete relevant medication information, such as anticoagulants, were not available in our datasets. Due to sample size, this study was underpowered to conduct a fully adjusted analysis.ConclusionAmong kidney transplant recipients, lower eGFR and presence of albuminuria at 1 year post-transplant were associated with an over 2-fold higher risk of hemorrhage and venous thrombosis. Graft function and albuminuria at 1 year post-transplant are important prognostic factors in determining risk of post-transplant hemorrhage and venous thrombosis. Further research, including medication data, are needed to further delineate outcomes and safety.Trial registrationNot applicable (cohort study).

Project description:Nonalcoholic steatohepatitis (NASH) is one of the top 3 indications for liver transplantation (LT) in Western countries. It is unknown whether renal dysfunction at the time of LT has any effect on post-LT outcomes in recipients with NASH. From the United Network for Organ Sharing-Standard Transplant Analysis and Research data set, we identified 4088 NASH recipients who received deceased donor LT. We divided our recipients a priori into 3 categories: group 1 with estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2 at the time of LT and/or received dialysis within 2 weeks preceding LT (n = 937); group 2 with recipients who had eGFR ≥30 mL/minute/1.73 m2 and who did not receive renal replacement therapy prior to LT (n = 2812); and group 3 with recipients who underwent simultaneous liver-kidney transplantation (n = 339). We examined the association of pretransplant renal dysfunction with death with a functioning graft, all-cause mortality, and graft loss using competing risk regression and Cox proportional hazards models. The mean ± standard deviation age of the cohort at baseline was 58 ± 8 years, 55% were male, 80% were Caucasian, and average exception Model for End-Stage Liver Disease score was 24 ± 9. The median follow-up period was 5 years (median, 1816 days; interquartile range, 1090-2723 days). Compared with group 1 recipients, group 2 recipients had 19% reduced trend for risk for death with a functioning graft (subhazard ratio [SHR], 0.81; 95% confidence interval [CI], 0.64-1.02) and similar risk for graft loss (SHR, 1.25; 95% CI, 0.59-2.62), whereas group 3 recipients had similar risk for death with a functioning graft (SHR, 1.23; 95% CI, 0.96-1.57) and graft loss (SHR, 0.18; 95% CI, 0.02-1.37) using an adjusted competing risk regression model. In conclusion, recipients with preserved renal function before LT showed a trend toward lower risk of death with a functioning graft compared with SLKT recipients and those with pretransplant severe renal dysfunction in patients with NASH.

Dataset Information

Pretransplant IgA-Anti-Beta 2 Glycoprotein I Antibodies As a Predictor of Early Graft Thrombosis after Renal Transplantation in the Clinical Practice: A Multicenter and Prospective Study.

Background

Methods

Setting and participants

Outcomes

Measurements

Results

Limitations

Conclusion

Publications

Pretransplant IgA-Anti-Beta 2 Glycoprotein I Antibodies As a Predictor of Early Graft Thrombosis after Renal Transplantation in the Clinical Practice: A Multicenter and Prospective Study.

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