title: Increased plasma catalytic iron in patients may mediate acute kidney injury and death following cardiac surgery.
abstract: Catalytic iron, the chemical form of iron capable of participating in redox cycling, is a key mediator of acute kidney injury (AKI) in multiple animal models, but its role in human AKI has not been studied. Here we tested in a prospective cohort of 250 patients undergoing cardiac surgery whether plasma catalytic iron levels are elevated and associated with the composite outcome of AKI requiring renal replacement therapy or in-hospital mortality. Plasma catalytic iron, free hemoglobin, and other iron parameters were measured preoperatively, at the end of cardiopulmonary bypass, and on postoperative days 1 and 3. Plasma catalytic iron levels, but not other iron parameters, rose significantly at the end of cardiopulmonary bypass and were directly associated with bypass time and number of packed red blood cell transfusions. In multivariate analyses adjusting for age and preoperative eGFR, patients in the highest compared with the lowest quartile of catalytic iron on postoperative day 1 had a 6.71 greater odds of experiencing the primary outcome, and also had greater odds of AKI, hospital mortality, and postoperative myocardial injury. Thus, our data are consistent with and expand on findings from animal models demonstrating a pathologic role of catalytic iron in mediating adverse postoperative outcomes. Interventions aimed at reducing plasma catalytic iron levels as a strategy for preventing AKI in humans are warranted.
authors.affiliation: Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Leaf
authors.affiliation: Department of Nephrology, Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India.
authors.forename: Mohan
authors.initials: M
authors.lastname: Rajapurkar
authors.affiliation: Department of Cardiology, Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India.
authors.forename: Suhas S
authors.initials: SS
authors.lastname: Lele
authors.affiliation: Department of Nephrology, Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India.
authors.forename: Banibrata
authors.initials: B
authors.lastname: Mukhopadhyay
authors.affiliation: Division of Cardiac Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Rawn
authors.affiliation: Department of Anesthesiology and Surgical Critical Care Translational Research Center, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Frendl
authors.affiliation: Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Sushrut S
authors.initials: SS
authors.lastname: Waikar
mesh_terms: D000136:Acid-Base Equilibrium; D058186:Acute Kidney Injury / Q000097:blood* / Q000209:etiology / Q000401:mortality / Q000628:therapy; D000209:Acute-Phase Proteins / Q000652:urine; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001900:Boston / Q000453:epidemiology; D006348:Cardiac Surgical Procedures / Q000009:adverse effects* / Q000401:mortality; D002315:Cardiopulmonary Bypass / Q000009:adverse effects* / Q000706:statistics & numerical data; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000097:blood*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D011183:Postoperative Complications / Q000097:blood* / Q000209:etiology / Q000401:mortality; D011184:Postoperative Period; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine; D017582:Renal Replacement Therapy / Q000706:statistics & numerical data
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D006454:Hemoglobins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D007501:Iron