title: Histopathological Evaluation of Contrast-Induced Acute Kidney Injury Rodent Models.
abstract: Contrast-induced acute kidney injury (CI-AKI) can occur in 3-25% of patients receiving radiocontrast material (RCM) despite appropriate preventive measures. Often patients with an atherosclerotic vasculature have to receive large doses of RCM. Thus, animal studies to uncover the exact pathomechanism of CI-AKI are needed. Sensitive and specific histologic end-points are lacking; thus in the present review we summarize the histologic appearance of different rodent models of CI-AKI. Single injection of RCM causes overt renal damage only in rabbits. Rats and mice need an additional insult to the kidney to establish a clinically manifest CI-AKI. In this review we demonstrate that the concentrating ability of the kidney may be responsible for species differences in sensitivity to CI-AKI. The most commonly held theory about the pathomechanism of CI-AKI is tubular cell injury due to medullary hypoxia. Thus, the most common additional insult in rats and mice is some kind of ischemia. The histologic appearance is tubular epithelial cell (TEC) damage; however severe TEC damage is only seen if RCM is combined by additional ischemia. TEC vacuolization is the first sign of CI-AKI, as it is a consequence of RCM pinocytosis and lysosomal fusion; however it is not sensitive as it does not correlate with renal function and is not specific as other forms of TEC damage also cause vacuolization. In conclusion, histopathology alone is insufficient and functional parameters and molecular biomarkers are needed to closely monitor CI-AKI in rodent experiments.
authors.affiliation: Institute of Pathophysiology, Semmelweis University, Budapest, Hungary.
authors.forename: Norbert
authors.identifier: 0000-0002-9947-1755
authors.initials: N
authors.lastname: Kiss
authors.affiliation: Institute of Pathophysiology, Semmelweis University, Budapest, Hungary.
authors.forename: Péter
authors.identifier: 0000-0002-1095-3564
authors.initials: P
authors.lastname: Hamar
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000473:pathology*; D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D006801:Humans; D007275:Injections, Intravenous; D007455:Iodine / Q000008:administration & dosage / Q000009:adverse effects*; D011817:Rabbits; D051381:Rats; D013045:Species Specificity
chemical_list: D003287:Contrast Media; D007455:Iodine