Transfusion of Pathogen-Reduced Red Blood Cells Yields Noninferior Outcomes for Acute Kidney Injury in Cardiac Surgery Patients

Strategic Insights -

Researchers from Yale University School of Medicine have conducted a phase 3 trial to investigate the safety and efficacy of transfusing amustaline/glutathione pathogen-reduced red blood cells in cardiac surgery patients with increased risk of red cell transfusion. The trial, which randomized 581 subjects, found that transfusion of pathogen-reduced red cells was noninferior to conventional transfusions for support of acute surgical blood loss. The study's primary endpoint was the proportion of patients with acute kidney injury (AKI), defined as an increase from baseline of greater than or equal to 0.3 mg/dl serum creatinine within 48 h of surgery. The results showed that the incidence of AKI was 29.3% in the pathogen-reduced arm and 28.0% in the conventional arm, with a treatment difference of 0.7% (95% CI, -8.9 to 10.4%; noninferiority margin, 14.0%; P = 0.001 for noninferiority). While AKI within 7 days by Kidney Disease Improving Global Outcomes staging criteria was not different between the two arms, stage III AKI was more common in the pathogen-reduced arm.

Key Takeaways:

  • The study involved a phase 3, double-blinded, noninferiority trial with 581 subjects, of which 321 (55%) were transfused with study red cells.
  • The primary endpoint was the proportion of patients with acute kidney injury (AKI), defined as an increase from baseline of greater than or equal to 0.3 mg/dl serum creatinine within 48 h of surgery.
  • The incidence of AKI was 29.3% in the pathogen-reduced arm and 28.0% in the conventional arm, with a treatment difference of 0.7% (95% CI, -8.9 to 10.4%; noninferiority margin, 14.0%; P = 0.001 for noninferiority).
  • AKI within 7 days by Kidney Disease Improving Global Outcomes staging criteria was not different between the two arms, but stage III AKI was more common in the pathogen-reduced arm (9.4% vs 4.3%).
  • The study concluded that treatment-emergent antibodies were uncommon and not clinically significant.
  • Edward L. Snyder, Edward L. of Laboratory Medicine at Yale University School of Medicine, was the lead researcher on the project.
  • Additional authors included Michael E. Sekela, Ian J. Welsby, Yoshiya Toyoda, Mohamed Alsammak, Neel R. Sodha, Thomas M. Beaver, J. Peter R. Pelletier, James D. Gorham, John S. McNeil, Roman M. Sniecinski, Ronald G. Pearl, Gregory A. Nuttall, Ravi Sarode, and T. Brett.

Statistics:

  • 581 subjects were randomized in the study
  • 321 (55%) subjects were transfused with study red cells
  • The incidence of AKI was 29.3% in the pathogen-reduced arm and 28.0% in the conventional arm
  • The treatment difference in AKI incidence was 0.7% (95% CI, -8.9 to 10.4%)
  • 15 of 159 (9.4%) patients in the pathogen-reduced arm developed stage III AKI, compared to 7 of 162 (4.3%) in the conventional arm
  • 5 (3.1%) patients in the pathogen-reduced arm developed specific, low-titer antibodies without evidence of hemolysis

Sources:

  • NewsRx LLC. Researchers from Yale University School of Medicine Report Findings in Acute Kidney Injury (Transfusion of Amustaline/Glutathione Pathogen-reduced Red Blood Cells in Cardiac Surgery: A Randomized Phase 3 Clinical Trial). Medical Devices & Surgical Technology Week. November 2, 2025; p 1893.
  • Transfusion of Amustaline/Glutathione Pathogen-reduced Red Blood Cells in Cardiac Surgery: A Randomized Phase 3 Clinical Trial. Anesthesiology, 2025;143(5):1196-1210.