Heme Oxygenase-1 and Acute Kidney Injury following Cardiac Surgery

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 anincrease 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.

2,3,5,6-Tetramethylpyrazine (TMP) down-regulated arsenic-induced heme oxygenase-1 and ARS2 expression by inhibiting Nrf2, NF-κB, AP-1 and MAPK pathways in human proximal tubular cells

“…The critical role of HO-1 has also been reported in several organ injuries (Wang and Dore 2007; Billings et al 2014). Given HO-1 also has been identified as a response biomarker for arsenic exposure in various types of cells, we were very interested: i) what is the role of HO-1 in As -induced nephrotoxicity (Gong et al 2014) at clinically relevant doses?…”

“…All these data mentioned above strongly demonstrated that HO-1 played a protective role in As -induced nephrotoxicity, and blocking HO-1 augmented As -induced cell death, ROS production and mitochondrial injury. In the other studies, HO-1 also has been shown to protect kidney against several acute kidney injury (AKI) (Billings et al 2014; Miyagi et al 2014; Goodman et al 2007). …”

Heme Oxygenase 1 as a Therapeutic Target in Acute Kidney Injury

“…145 Another study found increased levels of plasma HO-1 in patients who developed AKI following cardiopulmonary bypass; this is associated with duration of the bypass, hemolysis, and inflammation. 146 Given the overwhelming reliance on serum creatinine, urine output, and degree of proteinuria to monitor kidney function, the aforementioned findings of plasma and urinary HO-1 are timely and add to our armamentarium of biomarkers of AKI. However, it must also be noted that utilization of HO-1 as a novel biomarker of AKI requires additional investigation.…”

Acute kidney injury in cardiac surgery

“…Billings et al [59] examined the hypothesis that intravascular hemolysis induced during cardiac surgery releases plasma-free hemoglobin that in turn induces heme oxygenase-1. In patients who developed AKI after cardiac surgery, peak-free hemoglobin levels correlated with peak heme oxygenase-1, and heme oxygenase-1 levels increased with duration of CPB and interleukin activation.…”