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.

Renal Handling of Circulating and Renal-Synthesized Hepcidin and Its Protective Effects against Hemoglobin–Mediated Kidney Injury

“…41,42 During hemoglobin-induced AKI, circulating and filtered hepcidin may bind iron, which is, subsequently, internalized by the proximal tubules and as such, promotes renal cell sequestration. This is supported by the decrease of hemoglobin-induced elevation of urinary nonheme iron concentration.…”

Lung–Kidney Cross-Talk in the Critically Ill Patient

“…88 Catalytic iron, formation of obstructive casts and reduced NO bioavailability may impact vascular responses and multi-organ system function ( Figure 3). 89,90 The exposure of blood to the artificial surfaces can cause a hypercoagulable state and may reflect ongoing renovascular processes such as microvascular dysfunction and endothelial damage, leading to decreased renal oxygen supply. Hemorrhagic complications are the most commonly reported adverse events.…”

Heme Oxygenase 1 as a Therapeutic Target in Acute Kidney Injury

“…Recently, Leaf et al conducted a prospective cohort of 250 patients undergoing cardiac surgery and found a direct relationship between plasma catalytic iron levels and higher likelihood of AKI, hospital mortality, and postoperative myocardial injury. 139 While results from clinical trials using iron chelators in AKI have not been reported, targeting FtH may represent a novel strategy to sequester iron during AKI.…”