The pivotal role of a novel biomarker of reactive oxygen species in chronic kidney disease

Abstract

Risk stratification of chronic kidney disease (CKD) is clinically important because such patients are at high risk of cardiovascular events. Although reactive oxygen species (ROS) are reported to be closely associated with the pathophysiology of CKD, there are few useful ROS biomarkers known for CKD patients. Hence, our objectives in this study were to investigate whether serum derivatives of reactive oxygen metabolites (DROM), a novel biomarker of ROS, is involved in the pathophysiology of CKD (case-control study), and is a significant predictor of future cardiovascular events in CKD patients (follow-up study). Patients with suspected coronary artery disease (CAD) were enrolled and underwent coronary angiography. Patients with CKD (estimated glomerular filtration ratio <60mL/min/1.73m 2 and/or proteinuria, n=324) were compared with those without CKD (non-CKD). Serum DROM was measured at stable conditions. A case-control study of the 324 CKD patients and 263 non-CKD patients was conducted after matching risk factors, and a follow-up study of the 324 CKD patients was performed. CKD patients were divided into low- and high-DROM groups using their median value (348 unit; called the Carratelli unit [U.CARR]), and followed until the occurrence of cardiovascular events. DROM levels were significantly higher in risk factors-matched CKD patients than in risk factors-matched non-CKD patients (347.0 [301.8-391.8] U.CARR vs. 338.5 [299.8-384.3] U.CARR, P=0.03). During mean 23±14 months follow-up of 324 CKD patients, 83 cardiovascular events were recorded. Kaplan-Meier analysis demonstrated a higher probability of cardiovascular events in CKD patients with high DROM than in those with low DROM (P<0.001, log-rank test). Multivariate Cox hazard analysis including significant predictors in simple Cox hazard analysis demonstrated that high DROM was a significant and independent predictor of cardiovascular events in CKD patients (hazard ratio: 1.76, 95% confidence interval: 1.10-2.82, P=0.02). In conclusion, serum DROM values were significant and independent predictors of cardiovascular events in CKD patients, indicating that the measurements of DROM might provide clinical benefits for risk stratification of CKD patients.