Multiple lines of evidence support a central role of iron in causing acute kidney injury (AKI), including the finding that prophylactic administration of iron chelators attenuates AKI in animal models. Patients undergoing cardiac surgery may be particularly susceptible to iron-mediated kidney injury due to the profound hemolysis that often occurs from cardiopulmonary bypass. The investigators will test in a phase 2, randomized, double-blind, placebo-controlled trial whether prophylactic administration of deferoxamine decreases the incidence of AKI following cardiac surgery.

Inclusion Criteria:

1. Age ≥18 years
2. Undergoing coronary artery bypass graft and/or valve surgery with cardiopulmonary bypass
3. AKI risk score ≥6 at the time of screening
4. Written informed consent from the patient or surrogate

Exclusion Criteria:

1. AKI, defined as any of the following:

   • Increase in serum creatinine ≥0.3 mg/dl in 48h
   • Increase in serum creatinine ≥50% in 7d (if no value available in last 7d, use most recent value in last 3 months)
   • Urine output ≤0.5 ml/kg/h x 6 consecutive hours (only assessed in patients with hourly monitoring via Foley catheter)
   • Receipt of renal replacement therapy (RRT) within 7d

2. Advanced chronic kidney disease (eGFR <15 ml/min/1.73m2 or end-stage kidney disease receiving RRT)

3. Hemoglobin <8 g/dL (closest value in the prior 3 months)

4. Fever (temperature ≥38⁰C) in the last 48h

5. Suspected or confirmed bacteremia, endocarditis, or pyelonephritis

6. Pneumonia, aspiration, or bilateral pulmonary infiltrates from an infectious etiology reported on chest x-ray or CT scan in the last 7d

7. Positive COVID-19 test within previous 10d

8. Chronic iron overload (including conditions such as hemochromatosis and beta thalassemia major) or previous iron chelation therapy (including prior participation in DEFEAT-AKI)

9. Known hypersensitivity to deferoxamine

10. Taking prochlorperazine

11. Severe hearing loss

12. Pregnant or breastfeeding

13. Prisoner

14. Concurrent participation in another interventional research study in which the intervention has potential interaction with deferoxamine

15. Surgery to be performed under conditions of circulatory arrest

16. Receiving extracorporeal membrane oxygenation

17. Durable ventricular assist device (VAD) prior to surgery (does not include Impella device or intra-aortic balloon pump)

18. Any condition which, in the judgement of the investigator, might increase the risk to the patient

19. Conflict with other research studies

All-cause mortality was measured from initiation of the study drug until discharge from the index hospital admission during which the study drug was administered, up to 1 year; Vasoactive-Inotropic Score (VIS) was measured for 24-hours following study drug initiation; anaphylaxis was measured throughout the 12 hour study drug administration period; Infection/Sepsis and ARDS were measured for 7 days following the study drug administration.

We limited the scope of our adverse events (AEs) monitoring and reporting to a prespecified list of AEs of special interest (AESI)-anaphylaxis, infection/sepsis, VIS ≥ 30, and ARDS-since the patient population was undergoing high risk surgery and it was expected that they would have a number of unrelated adverse health events during the course of their hospital stay.