Circulating mitochondrial dysfunction as an early biomarker for contrast media-induced acute kidney injury in chronic kidney disease patients

Contrast-induced acute kidney injury (CI-AKI) is the common hospitalized acute kidney injury (AKI). However, the diagnosis by serum creatinine might not be early enough. Currently, the roles of circulating mitochondria in CI-AKI are still unclear. Since early detection is crucial for treatment, the association between circulating mitochondrial function and CI-AKI was tested as a potential biomarker for detection of CI-AKI. Twenty patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) were enrolled. Blood and urine samples were obtained at the time of PCI, and 6, 24, 48 and 72 h after PCI. Plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) were measured. Oxidative stress, inflammation, mitochondrial function, mitochondrial dynamics and cell death were determined from peripheral blood mononuclear cells. Forty percent of patients developed AKI. Plasma NGAL levels increased after 24 h after receiving contrast media. Cellular and mitochondrial oxidative stress, mitochondrial dysfunction and decreased mitochondrial fusion occurred at 6 h following contrast media exposure. Subgroup of AKI had higher %necroptosis cells and TNF-alpha mRNA expression than subgroup without AKI. Collectively, circulating mitochondrial dysfunction could be an early predictive biomarker for CI-AKI in CKD patients receiving contrast media. These findings provide novel strategies to prevent CI-AKI according to its pathophysiology.

Automated summary

Contrast-induced acute kidney injury (CI-AKI) is a common type of acute kidney injury in hospitalized patients. However, diagnosing CI-AKI using serum creatinine may not be early enough. This study aimed to investigate the role of circulating mitochondrial dysfunction as a potential early biomarker for detecting CI-AKI. Twenty patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) were included. Blood and urine samples were collected at different time points after PCI to measure neutrophil gelatinase-associated lipocalin (NGAL) levels and assess oxidative stress, inflammation, mitochondrial function, dynamics, and cell death. The results showed that 40% of patients developed AKI, and plasma NGAL levels increased after 24 hours of receiving contrast media. Cellular and mitochondrial oxidative stress, dysfunction, and decreased fusion occurred 6 hours after contrast media exposure. The subgroup with AKI had higher necroptosis cells and TNF-alpha mRNA expression compared to the subgroup without AKI. In conclusion, circulating mitochondrial dysfunction could serve as an early predictive biomarker for CI-AKI in CKD patients receiving contrast media. These findings provide insights for the development of novel strategies to prevent CI-AKI based on its pathophysiology.