Contrast Induced Acute Kidney Injury and Direct Cytotoxicity of Iodinated Radiocontrast Media on Renal Proximal Tubule Cells

Abstract

The administration of intravenous iodinated radiocontrast media (RCM) to visualize internal structures during diagnostic procedures has increased exponentially since their first use in 1928. A serious side effect of RCM exposure is contrast-induced acute kidney injury (CI-AKI), which is defined as an abrupt and prolonged decline in renal function occurring 48-72 hours after injection. Multiple attempts have been made to decrease the toxicity of RCM by altering ionic strength and osmolarity, yet there is little evidence to substantiate that a specific RCM is superior in avoiding CI-AKI. RCM-associated kidney dysfunction is largely attributed to alterations in renal hemodynamics, specifically renal vasoconstriction; however, numerous studies indicate direct cytotoxicity as a source of epithelial damage. Exposure of in vitro renal proximal tubule cells to RCM has been shown to affect proximal tubule epithelium in the following manner: 1) changes to cellular morphology in the form of vacuolization; 2) increased production of reactive oxygen species, resulting in oxidative stress; 3) mitochondrial dysfunction, resulting in decreased efficiency of the electron transport chain and ATP production; 4) perturbation of the protein folding capacity of the endoplasmic reticulum (ER) (activating the unfolded protein response and inducing ER stress); and 5) decreased activity of cell survival kinases. The present review focuses on the direct cytotoxicity of RCM on proximal tubule cells in the absence of in vivo complications, such as alterations in renal hemodynamics or cytokine influence.

Anti-Apoptotic and Antioxidant Effects of 3-Epi-Iso-Seco-Tanapartholide Isolated from Artemisia argyi against Iodixanol-Induced Kidney Epithelial Cell Death

“…As a comparative study, the protective effects of 9 sesquiterpenes against iodixanol-induced cell damage caused by iodixanol in LLC-PK1 cells were evaluated. Iodixanol-induced cytotoxicity may affect changes in cellular energy metabolism and renal epithelial cell monolayers [ 26 , 27 ]. Interestingly, iso- seco -tanapartholide (compound 9 ) exhibited no protective effect on iodixanol-induced LLC-PK1 cell death, whereas the approximately 60% survival of LLC-PK1 cells after treatment with iodixanol was increased to over 80% after pretreatment with 3-epimer of compound 9 , compound 8 at the nontoxic concentration.…”

Stanniocalcin-1 Alleviates Contrast-Induced Acute Kidney Injury by Regulating Mitochondrial Quality Control via the Nrf2 Pathway

“…Many pathophysiological processes contribute to the development of CI-AKI, such as renal medullary ischemia, direct tubular cytotoxicity of contrast, overproduction of reactive oxygen species (ROS), mitochondrial damage, and mitophagy [1,[6][7][8][9]. Most guidelines suggest that expanding intravascular volume is more reasonable in preventing CI-AKI [10,11].…”

Protective effect of glycyrrhizin, a direct HMGB1 inhibitor, on post-contrast acute kidney injury

“…PC-AKI is thought to be caused by both renal hemodynamic changes and direct renal parenchymal damage. 21 The latter might be due to the direct toxicity of iodine contained in the contrast media to the tubular epithelial cells and endothelial cells or due to enhanced production of ROS by the contrast media, resulting in increased oxidative stress. 2,21 Hence, the cytotoxicity of contrast media might be ameliorated by reducing oxidative stress.…”