Biomarkers in Contrast-Induced Acute Kidney Injury: Towards A New Perspective

Abstract

Contrast-Induced Acute Kidney Injury (CI-AKI) remains a frequent iatrogenic condition since radiological procedures using intra-vascular iodinated contrast media (CM) are being widely administered for diagnostic and therapeutic purposes. Despite the improvement of the medical healthcare system worldwide, CI-AKI is still associated with direct short-term and indirect long-term outcomes including increased morbidity and mortality, especially in patients with underlying pre-existing renal function impairment, cardiovascular disease, or diabetes that could rapidly progress into Chronic Kidney Disease. Although the RIFLE (Risk, Injury, Failure, Loss, End-Stage Kidney Disease), AKIN (Acute Kidney Injury Network), and KDIGO (Kidney Disease Improving Global Outcomes) clinical criteria and recommendation guidelines are based on traditional "gold standard" biomarkers known as serum creatinine, glomerular filtration rate, and urinary output, new reliable serum and urinary biomarkers are still needed for an effective unified diagnostic strategy for AKI. Starting from previous and recent publications on the benefits and limitations of validated biomarkers responding to kidney injury, glomerular filtration, and inflammation among others, this review unravels the role of new emerging biomarkers used alone or in combination as reliable tools for early diagnosis and prognosis of CI-AKI, taking into account patients and procedures-risk factors towards a new clinical perspective.

Keywords: biomarkers; contrast media; contrast-induced acute kidney injury; nephrotoxicity.

Figure 1

Contrast-induced acute kidney injury (CI-AKI) pathophysiology. Contrast media (CM) mediates, on the other hand, direct renal tubular and endothelial cytotoxicity, leading to increased intrarenal pressure and consequent increase of intratubular pressure, resulting in a vicious cycle of medullary hypoxia, oxidative stress and increased loss of function, integrity, and cell death. On the other hand, the viscous properties of CM trigger vasoconstriction increase blood viscosity, which reduces urinary flow rate, decreases microvascularization, and increases the risk of microvascular thrombosis. All this leads to an abrupt loss of renal function resulting in CI-AKI. P, pressure; ROS, reactive oxygen species; GFR, glomerular filtration rate.

Figure 2

Traditional and novel biomarkers classification. CysC, Cystatin C; NGAL, Neutrophil Gelatinase-Associated Lipocalin; KIM-1, Kidney Injury Molecule-1; IGFBP, Insulin-like Growth Factor-Binding Protein; TIMP, Tissue Inhibitor of Metalloproteinase; L-FABP, Liver Fatty Acid-Binding Protein; NAG, N-Acetyl-β-D-Glucosaminidase; GST, α-Glutathione S-Transferase; MCP-1, Monocyte Chemoattractant Protein-1; IL, Interleukin; CTGF, Connective Tissue Growth Factor; VEGF, Vascular Endothelial Growth Factor; OPN, Osteopontin; FENA, Fractional Excretion of Sodium; RBP, Retinol Binding Protein; VDBP, Vitamin D Binding Protein; GGT, Gamma-glutamyltransferase activity; MK, Midkine; miRNAs, microRNA.