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

Abstract

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-α 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.

Keywords: cell death; contrast-induced acute kidney injury; inflammation; mitochondrial dynamics; oxidative stress.