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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.
Insights
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.
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.
Abstract:
AKI after cardiac surgery is associated with mortality, prolonged hospital length of stay, use of dialysis, and subsequent CKD. We evaluated the effects of THR-184, a bone morphogenetic protein-7 agonist, in patients at high risk for AKI after cardiac surgery. We conducted a randomized, double-blind, placebo-controlled, multidose comparison of the safety and efficacy of perioperative THR-184 using a two-stage seamless adaptive design in 452 patients between 18 and 85 years of age who were scheduled for nonemergent cardiac surgery requiring cardiopulmonary bypass and had recognized risk factors for AKI. The primary efficacy end point was the proportion of patients who developed AKI according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The proportion of patients who developed AKI within 7 days of surgery was similar in THR-184 treatment groups and placebo groups (range, 74%-79%; P=0.43). Prespecified secondary end point analysis did not show significant differences in the severity of AKI stage (P=0.53) or the total duration of AKI (P=0.44). A composite of death, dialysis, or sustained impaired renal function by day 30 after surgery did not differ between groups (range, 11%-20%; P=0.46). Safety-related outcomes were similar across all treatment groups. In conclusion, compared with placebo, administration of perioperative THR-184 through a range of dose exposures failed to reduce the incidence, severity, or duration of AKI after cardiac surgery in high-risk patients.
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