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    Renal Function Improvement Following ANG-3777 Treatment in Patients at High Risk for Delayed Graft Function After Kidney Transplantation

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    Author
    Bromberg, J.S.
    Weir, M.R.
    Gaber, A.O.
    Yamin, M.A.
    Goldberg, I.D.
    Mayne, T.J.
    Cal, W.
    Cooper, M.
    Date
    2021
    Journal
    Transplantation
    Publisher
    Wolters Kluwer Health
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1097/TP.0000000000003255
    Abstract
    Background: Patients (20%–50%) undergoing renal transplantation experience acute kidney injury resulting in delayed graft function. ANG-3777 is an hepatocyte growth factor mimetic that binds to the c-MET receptor. In animal models, ANG-3777 decreases apoptosis, increases proliferation, and promotes organ repair and function. Methods: This was a randomized, double-blind, placebo-controlled, phase 2 trial of patients undergoing renal transplantation with <50 cc/h urine output for 8 consecutive hours over the first 24 hours posttransplantation, or creatinine reduction ratio <30% from pretransplantation to 24 hours posttransplantation. Subjects were randomized as 2:1 to 3, once-daily IV infusions of ANG-3777, 2 mg/kg (n = 19), or placebo (n = 9). Primary endpoint: time in days to achieve ≥1200 cc urine for 24 hours. Results: Patients treated with ANG-3777 were more likely to achieve the primary endpoint of 1200 cc urine for 24 hours by 28 days posttransplantation (83.3% versus 50% placebo; log-rank test: χ2 = 2.799, P = 0.09). Compared with placebo, patients in the ANG-3777 arm had larger increases in urine output; lower serum creatinine; greater reduction in C-reactive protein and neutrophil gelatinase-associated lipocalin; fewer dialysis sessions and shorter duration of dialysis; fewer hospital days; significantly less graft failure; and higher estimated glomerular filtration rate. Adverse events occurred in a similar percentage of subjects in both arms. Events per subject were twice as high in the placebo arm. Conclusions: There was an efficacy signal for improved renal function in subjects treated with ANG-3777 relative to placebo, with a good safety profile. Copyright 2020 The Author(s). Published by Wolters Kluwer Health, Inc.
    Keyword
    ANG-3777
    Kidney Transplantation
    Acute Kidney Injury--prevention & control
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/15247
    ae974a485f413a2113503eed53cd6c53
    10.1097/TP.0000000000003255
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