SOD1 is a novel prognostic biomarker of acute kidney injury following cardiothoracic surgery

Abstract

Background: Acute kidney injury (AKI) is a major burden among hospitalized and critical care patients. Among hospitalized patients that progress to severe AKI there is increased risk for morbidity, mortality, and the need for renal replacement therapy (RRT). As there are no specific treatments for AKI, the discovery of novel biomarkers that predict the progression of AKI may aid in timely implementation of supportive care to improve outcomes.

Methods: We collected urine from 204 patients that developed Stage 1 AKI by AKIN criteria within 72 h following cardiothoracic surgery. Urine samples were collected at the time of the initial diagnosis of AKI and stored at ^-80° C. Among the 204 patients, 25 progressed to a composite primary outcome of Stage 3 AKI, requirement of RRT, or 30-day mortality. The remaining 179 patients did not progress beyond Stage 2 AKI and were considered controls. Urinary concentrations of SOD1 and SOD1 activity were measured following collection of all samples. Samples were thawed and urinary superoxide dismutase 1 (SOD1) concentrations were measured by sandwich ELISA and urinary SOD1 activity was measured through a commercially available colorimetric assay.

Results: Urinary concentrations of SOD1 were significantly elevated (67.0 ± 10.1 VS 880.3 ± 228.8 ng/ml, p < 0.0001) in patients that progressed to severe AKI and were able to predict the progression to severe AKI (AUC - 0.85, p < 0.0001). Furthermore, total SOD activity also increased in the urine of patients that required RRT (77.6% VS 49.81% median inhibition, p < 0.01) and was able to predict the need for RRT (AUC: 0.83, p < 0.01).

Conclusion: These findings show that urinary SOD1 concentrations and SOD activity are novel prognostic biomarkers for severe AKI following cardiothoracic surgery.

Keywords: Acute kidney injury; Biomarkers; Renal replacement therapy; SOD1.