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Perioperative THR-184 and AKI after Cardiac Surgery.

Jonathan Himmelfarb1, Glenn M Chertow2, Peter A McCullough3

  • 1Department of Medicine, Kidney Research Institute, University of Washington, Seattle, Washington; Jhimmelfarb@nephrology.washington.edu.

Journal of the American Society of Nephrology : JASN
|December 6, 2017
PubMed
Summary

Perioperative THR-184, a bone morphogenetic protein-7 agonist, did not reduce the incidence or severity of acute kidney injury (AKI) in high-risk cardiac surgery patients. This study found no significant benefit of THR-184 over placebo for AKI prevention.

Keywords:
acute renal failurebone morphogenetic proteinrandomized controlled trials

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Area of Science:

  • Nephrology
  • Cardiology
  • Pharmacology

Background:

  • Acute kidney injury (AKI) following cardiac surgery is a significant complication linked to increased mortality, prolonged hospitalization, dialysis requirements, and chronic kidney disease (CKD).
  • Identifying effective interventions to prevent AKI in high-risk surgical patients remains a critical clinical challenge.

Purpose of the Study:

  • To evaluate the efficacy and safety of THR-184, a bone morphogenetic protein-7 (BMP-7) agonist, in preventing acute kidney injury (AKI) in patients undergoing cardiac surgery.
  • To assess the impact of THR-184 on AKI incidence, severity, duration, and associated adverse outcomes in a high-risk population.

Main Methods:

  • A randomized, double-blind, placebo-controlled, multidose study involving 452 high-risk adult patients scheduled for nonemergent cardiac surgery with cardiopulmonary bypass.
  • Patients received perioperative THR-184 or placebo, with AKI assessed using Kidney Disease Improving Global Outcomes (KDIGO) criteria.
  • Primary endpoint: proportion of patients developing AKI within 7 days. Secondary endpoints included AKI severity, duration, and a composite of death, dialysis, or sustained renal impairment at 30 days.

Main Results:

  • The incidence of AKI within 7 days post-surgery was similar between THR-184 and placebo groups (74%-79%, P=0.43).
  • No significant differences were observed in AKI severity (P=0.53), total AKI duration (P=0.44), or the composite endpoint of death, dialysis, or impaired renal function at 30 days (P=0.46).
  • Safety outcomes were comparable across all treatment arms, indicating no increased safety concerns with THR-184 administration.

Conclusions:

  • Perioperative administration of THR-184, a BMP-7 agonist, failed to demonstrate efficacy in reducing the incidence, severity, or duration of acute kidney injury after cardiac surgery in high-risk patients.
  • The findings suggest that THR-184 is not an effective therapeutic agent for preventing AKI in this specific perioperative setting.