Plasma Catalytic Iron, AKI, and Death among Critically Ill Patients

Abstract

Background and objectives Catalytic iron has been hypothesized to be a key mediator of AKI. However, the association between plasma catalytic iron levels and AKI has not been well studied in humans.Design, settings, participants, & measurements A single-center, prospective, nonconsecutive cohort study of 121 critically ill patients admitted to intensive care units (ICUs) between 2008 and 2012 was performed. Plasma catalytic iron, free hemoglobin, and other iron markers were measured on ICU days 1 and 4. The primary end point was in-hospital mortality or AKI requiring RRT. Secondary end points included mortality (assessed during hospitalization, at 30 days, and 1 year) and incident AKI, defined by modified Kidney Disease Improving Global Outcomes criteria.Results ICU day 1 plasma catalytic iron levels were higher among patients who reached the primary end point (median, 0.74 mmol/l [interquartile range, 0.31-3.65] versus 0.29 mmol/l [0.22-0.46]; P,0.01). ICU day 1 plasma catalytic iron levels were associated with number of packed red blood cell transfusions before ICU arrival (r s =0.29; P,0.001) and plasma free hemoglobin levels on ICU day 1 (r s =0.32; P,0.001). Plasma catalytic iron levels on ICU day 1 were significantly associated with in-hospital mortality or AKI requiring RRT, even after adjusting for age, enrollment eGFR, and number of packed red blood cell transfusions before ICU arrival (13 events; adjusted odds ratio per 1-SD higher ln[catalytic iron], 3.33; 95% confidence interval, 1.79 to 6.20). ICU day 1 plasma catalytic iron levels were also significantly associated with incident AKI, RRT, hospital mortality, and 30-day mortality.Conclusions Among critically ill patients, elevated plasma catalytic iron levels on arrival to the ICU are associated with a greater risk of incident AKI, RRT, and hospital mortality.

AKI Associated with Cardiac Surgery

“…Since that time, additional studies have added to the growing body of literature suggesting that anemia and the use of packed red blood cells are independent risk factors for AKI after cardiac surgery (145)(146)(147). Catalytic iron (i.e., circulating iron not bound to any proteins) can produce hydroxyl radicals, cause oxidative tissue damage, and has been proposed as a nephrotoxin (148). A recent analysis of catalytic iron levels in a population of patients who were critically ill found a strong relationship between the amount of blood products transfused and catalytic iron levels as well as between catalytic iron levels and the probability of developing AKI, suggesting a potential mechanism for the relationship between blood product transfusion and AKI (148).…”

Heme Oxygenase 1 as a Therapeutic Target in Acute Kidney Injury

“…136, 137 Based on experimental and human studies, iron is increasingly recognized to be a major culprit in AKI. 138–140 To study iron trafficking and its role in AKI, we recently generated a novel transgenic mouse model with conditional deletion of heavy chain ferritin (FtH) in renal proximal tubules. 100 Interestingly, these mice exhibit significantly higher levels of HO-1 expression both under basal and injury conditions.…”

Predictive value of iron parameters in neurocritically ill patients

“…Bobbio‐Pallavicini et al () investigated 51 postoperative critically ill patients and found that the increase in ferritin concentration correlated with worsening of the clinical status. In a prospective observational cohort study of 121 critically ill patients, plasma catalytic iron levels on ICU day 1 were significantly associated with hospital mortality and 30‐day mortality (Leaf et al, ). These results could be explained by the common inflammation, especially infectious inflammation, in critically ill patients.…”