RT Journal Article
SR Electronic
T1 Contrast Induced Acute Kidney Injury and Direct Cytotoxicity of Iodinated Radiocontrast Media on Renal Proximal Tubule Cells
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 160
OP 171
DO 10.1124/jpet.119.257337
VO 370
IS 2
A1 Dakota B. Ward
A1 Monica A. Valentovic
YR 2019
UL http://jpet.aspetjournals.org/content/370/2/160.abstract
AB 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.