HO-1 concentrations 24 hours after cardiac surgery are associated with the incidence of acute kidney injury: a prospective cohort study

Abstract

Background: Acute kidney injury (AKI) is a serious complication after cardiac surgery that is associated with increased mortality and morbidity. Heme oxygenase-1 (HO-1) is an enzyme synthesized in renal tubular cells as one of the most intense responses to oxidant stress linked with protective, anti-inflammatory properties. Yet, it is unknown if serum HO-1 induction following cardiac surgical procedure involving cardiopulmonary bypass (CPB) is associated with incidence and severity of AKI.

Patients and methods: In the present study, we used data from a prospective cohort study of 150 adult cardiac surgical patients. HO-1 measurements were performed before, immediately after and 24 hours post-CPB. In univariate and multivariate analyses, the association between HO-1 and AKI was investigated.

Results: AKI with an incidence of 23.3% (35 patients) was not associated with an early elevation of HO-1 after CPB in all patients (P=0.88), whereas patients suffering from AKI developed a second burst of HO-1 24 hours after CBP. In patients without AKI, the HO-1 concentrations dropped to baseline values (P=0.031). Furthermore, early HO-1 induction was associated with CPB time (P=0.046), while the ones 24 hours later lost this association (P=0.219).

Conclusion: The association of the second HO-1 burst 24 hours after CBP might help to distinguish between the causality of AKI in patients undergoing CBP, thus helping to adapt patient stratification and management.

Keywords: acute kidney injury; cardiac surgery; cardiopulmonary bypass; heme oxygenase-1.

Figure 1

Creatinine levels preoperatively, at arrival in ICU, and 24 and 48 hours postoperatively for patients with and without AKI occurring within 48 hours postoperatively. Notes: 0 refers to no AKI in 48 hours after surgery and 1 refers to AKI 48 hours after surgery. The circles and stars are markers in our statistics software SPSS. The circles represent “out” values and stars represent “far out” values, based on interquartile range. Abbreviations: AKI, acute kidney injury; AKI_48, acute kidney injury 48 hours after cardiac surgery; HO-1, heme oxygenase 1; ICU, intensive care unit.

Figure 2

Plasma NGAL levels preoperatively and at arrival in ICU for patients with and without AKI occuring within 48 hours after cardiac surgery. Notes: 0 refers to no AKI in 48 hours after surgery and 1 refers to AKI 48 hours after surgery. The circles and stars are markers in our statistics software SPSS. The circles represent “out” values and stars represent “far out” values, based on interquartile range. Abbreviations: AKI, acute kidney injury; AKI_48, acute kidney injury 48 hours after cardiac surgery; ICU, intensive care unit; NGAL, neutrophil gelatinase-associated lipocalin.

Figure 3

Plasma HO-1 levels preoperatively, at arrival in ICU, and 24 hours postoperatively for patients with and without AKI occurring within 48 hours postoperatively. Notes: 0 refers to no AKI in 48 hours after surgery and 1 refers to AKI 48 hours after surgery. The circles and stars are markers in our statistics software SPSS. The circles represent “out” values and stars represent “far out” values, based on interquartile range. Abbreviations: AKI, acute kidney injury; AKI_48, acute kidney injury 48 hours after cardiac surgery; HO-1, heme oxygenase 1; ICU, intensive care unit; NGAL, neutrophil gelatinase-associated lipocalin.

Figure 4

ROC curves showing the interaction between creatinine levels at 6, 24, and 48 hours postop, NGAL immediately postop, and serum HO-1 levels 24 hours postop, for the prediction of any stages of AKI occurring within 48 hours postoperatively. Note: Diagonal segments are produced by ties. Abbreviations: AKI, acute kidney injury; crea, creatinine; Crea, creatinine; HO-1, heme oxygenase 1; NGAL, neutrophil gelatinase-associated lipocalin; postop, postoperative; ROC, receiver operating characteristic.

Figure 5

ROC curves for serum HO-1 levels 24 hours postoperatively for the prediction of any stage of AKI (A) and stage 2 or 3 AKI (B) occurring within 48 hours postoperatively. Abbreviations: AKI, acute kidney injury; HO-1, heme oxygenase 1; ROC, receiver operating characteristic.