The Association Between Serum Glutathione Peroxidase-3 Concentration and Risk of Acute Kidney Injury After Cardiac Surgery: A Nested Case-Control Study

Oxidative stress has an integral role in the pathophysiology of cardiac surgery-associated acute kidney injury (CSA-AKI). Glutathione peroxidase 3 (GPx3) is an important antioxidant enzyme in circulation and is mainly secreted by the kidney. This study aimed to evaluate the relation between GPx3 protein and CSA-AKI. This study is a nested case-control study in Zhongshan Hospital affiliated with Fudan University. We examined serum samples from 80 CSA-AKI patients and 80 age- and gender-matched non-AKI patients who underwent cardiac surgery. AKI was defined according to Kidney Disease: Improving Global Outcomes (KDIGO) 2012 criteria. We measured serum GPx3 concentration using the enzyme-linked immunosorbent assay. GPx3 ratio is the ratio of preoperative and 6 hours postoperative of GPx3 protein concentration. We applied dose-response relation analyses to odds ratio in different GPx3 ratio levels and integrated it into the logistic model to predict the risk of AKI. The receiver operating characteristic curve and area under the curve (AUC) was used to assess the prediction models. Postoperative serum GPx3 concentrations were significantly lower in the AKI group compared with the non-AKI group (1.78 +/- 0.33 vs 2.03 +/- 0.27, p <0.001). Malondialdehyde was higher in the AKI than in the non-AKI group (17.74 +/- 8.65 vs 7.48 +/- 4.59, p <0.001). The AKI risk increased in a dose-dependent manner, which was flat in the first half of the GPx3 ratio and then tended to be faster. The peaking odds ratio of CSA-AKI was 2.615 at the GPx3 ratio of 1.21 to 1.40. The AUC value to predict CSA-AKI only included the GPx3 ratio was 72.3%. After gradually integrating other covariates (body mass index, aortic crossclamp time, and cardiopulmonary bypass), the model showed an AUC of 82.6%. The serum GPx3 concentration was significantly lower in the CSA-AKI group. GPx3 ratio has a good predictive value for CSA-AKI, which may be a potential early diagnostic marker for AKI.(c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC license (http://creativecommons.org/ licenses/by-nc/4.0/) (Am J Cardiol 2023;209:29-35)

Automated summary

Oxidative stress plays an important role in cardiac surgery-associated acute kidney injury. Serum GPx3 concentration is lower in CSA-AKI patients, and the GPx3 ratio can be used to predict the risk of CSA-AKI.