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. 2014 Apr;4(1):12-21.
doi: 10.1159/000357871. Epub 2014 Jan 15.

Heme Oxygenase-1 and Acute Kidney Injury following Cardiac Surgery

Frederic T Billings 4th  1 , Chang Yu  2 , John G Byrne  3 , Michael R Petracek  3 , Mias Pretorius  4
Affiliations

Heme Oxygenase-1 and Acute Kidney Injury following Cardiac Surgery

Frederic T Billings 4th et al. Cardiorenal Med. 2014 Apr.

Erratum in

  • Cardiorenal Med. 2014;4(2):139. Billings, Frederic T [corrected to Billings, Frederic T 4th]

Abstract

Background: Intraoperative hemolysis and inflammation are associated with acute kidney injury (AKI) following cardiac surgery. Plasma-free hemoglobin induces heme oxygenase-1 (HO-1) expression. HO-1 degrades heme but increases in experimental models of AKI. This study tested the hypothesis that plasma HO-1 concentrations are associated with intraoperative hemolysis and are increased in patients that develop AKI following cardiac surgery.

Methods: We measured plasma HO-1, free hemoglobin, and inflammatory markers in 74 patients undergoing cardiopulmonary bypass (CPB). AKI was defined as an increase in serum creatinine concentration of 50% or 0.3 mg/dl within 72 h of surgery.

Results: Twenty-eight percent of patients developed AKI. HO-1 concentrations increased from 4.2 ± 0.2 ng/ml at baseline to 6.6 ± 0.5 ng/ml on postoperative day (POD) 1 (p < 0.001). POD1 HO-1 concentrations were 3.1 ng/ml higher (95% CI 1.1-5.1) in AKI patients, as was the change in HO-1 from baseline to POD1 (4.4 ± 1.3 ng/ml in AKI patients vs. 1.5 ± 0.3 ng/ml in no-AKI patients, p = 0.006). HO-1 concentrations remained elevated in AKI patients even after controlling for AKI risk factors and preoperative drug therapy. Peak-free hemoglobin concentrations correlated with peak HO-1 concentrations on POD1 in patients that developed AKI (p = 0.02). Duration of CPB and post-CPB IL-6 and IL-10 concentrations were also associated with increased HO-1 on POD1.

Conclusion: Plasma HO-1 is increased in patients that develop AKI, and CPB duration, hemolysis, and inflammation are associated with increased HO-1 concentrations following cardiac surgery. Strategies that alter hemolysis and HO-1 expression during cardiac surgery may affect risk for AKI.

Keywords: Acute kidney injury; Angiotensin-converting enzyme inhibitor; Cardiac surgery; Cardiopulmonary bypass; Heme oxygenase-1; Hemoglobin; Hemolysis; Interleukin.

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Figures

Fig. 1
Fig. 1
HO-1 concentrations in patients undergoing CPB. HO-1 concentrations were higher in patients that developed AKI compared to those that did not.
Fig. 2
Fig. 2
Correlations between POD1 HO-1 and duration of CPB (a), post-CPB free hemoglobin (b), post-CPB IL-6 (c), and post-CPB IL-10 (d) in patients that did and did not develop AKI.
Fig. 3
Fig. 3
Plasma-free hemoglobin concentrations in patients undergoing CPB. Free hemoglobin concentrations were higher in patients that developed AKI compared to those that did not.
Fig. 4
Fig. 4
Inflammatory response to CPB as measured by IL-6 (a), IL-8 (b), and IL-10 (c). IL-6 concentrations were significantly higher in patients that developed AKI compared to those that did not.
See this image and copyright information in PMC

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