Kidney Week

Abstract: SA-OR007

Preoperative Immunoneutralization of Endogenous Ouabain Lowers the Risk for AKI Evoked by Cardiac Bypass Graft Surgery

Session Information

• AKI Advances: Biomarkers, Outcomes, and Clinical Trials
  November 08, 2025 | Location: Room 320A, Convention Center
  Abstract Time: 05:30 PM - 05:40 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Blaustein, Mordecai P., University of Maryland Baltimore, Baltimore, Maryland, United States

Mordecai P. Blaustein, MD

• Hamlyn, John, University of Maryland Baltimore, Baltimore, Maryland, United States

John Hamlyn, PhD

• Suber, Tameka Deshawn, University of Maryland Baltimore, Baltimore, Maryland, United States

Tameka Deshawn Suber, MS

• Gottlieb, Eric Raphael, Harvard Medical School, Boston, Massachusetts, United States

Eric Raphael Gottlieb, MD

• Salenger, Rawn, University of Maryland Baltimore, Baltimore, Maryland, United States

Rawn Salenger, MD

• Christenson, Robert, University of Maryland Baltimore, Baltimore, Maryland, United States

Robert Christenson, PhD

• Gottlieb, Stephen S., University of Maryland Baltimore, Baltimore, Maryland, United States

Stephen S. Gottlieb, MD

Group or Team Name

• PORDOA.

Background

Acute kidney injury (AKI) impacts ~12-30% of patients post CABG surgery. Elevated pre-op plasma levels of endogenous ouabain (EO) may predict increased risk of AKI post CABG. Further, in cultured rodent renal cells, subnanomolar ouabain concentrations decreased nephrin expression & in vivo, increased plasma creatinine & proteinuria in rats. To asses the potential role for elevated circulating EO as a driver for AKI in man, we immunoneutralized circulating EO pre-op with DigiFab among patients at high risk for CABG-evoked AKI.

Methods

Baseline values (creatinine, free EO and biomarkers cystatin C, NGAL & KIM-1) were measured in 250 patients in a double-blind randomized study. Patients received 80 mg Digifab i.v., or an equivalent volume (placebo) 1 hour pre-op &, if in-hospital, also 12-15 hours prior to surgery. For EO, follow-up values were obtained at 0-4 hr and 3 days post-op. Endpoints: AKI by 3 days post-op in patients with pre-op free EO above the median of 361 pM (high EO), & changes in eGFR & biomarkers of renal function.

Results

Circulating free EO declined in all patients receiving DigiFab @ 0-4 (P<0.0001) and remained lower @ 3 days (P<0.04) post-op. Free EO was unchanged in placebo. In patients with high pre-op EO, the incidence of AKI was lower in the DigiFab (5/59, 8.5%) vs Placebo group (12/66, 18.2%). Among patients with high pre-op EO, and after controlling for baseline estimated GFR, the rate of AKI was significantly reduced (OR 0.274, 95 % CI [0.073-0883], p=0.039 in the DigiFab group. In patients with low pre-op EO, 16/125 (12.8%) developed AKI and DigiFab had no effect. No differences were found between groups for biomarkers or eGFR. No adverse effects of DigiFab were observed.

Conclusion

Elevated pre-op EO levels were linked previously with heightened risk for post-op AKI following CABG. DigiFab reduced free EO levels & the incidence of AKI. The beneficial impact was selective for patients with elevated pre-op EO. We conclude that elevated pre-op EO levels appear to contribute actively to the risk for post-op AKI in some patients. Immunoneutralization of EO in high-risk patients may represent an effective and safe means to reduce the incidence of CABG-evoked AKI with the added potential for long-term clinical benefit.

Funding

• Commercial Support – Serb Pharmaceuticals

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025ybtgtatn