title: A novel contrast-induced acute kidney injury model based on the 5/6-nephrectomy rat and nephrotoxicological evaluation of iohexol and iodixanol in vivo.
abstract: Contrast-induced acute kidney injury (CI-AKI) is a serious complication in patients after administration of iodinated contrast media. Proper animal models of CI-AKI can help understand the mechanisms involved and prevent the disorder. We used the 5/6-nephrectomized (NE) rat to develop a CI-AKI model and to evaluate differences in the toxic effects on the kidney between iohexol and iodixanol. We found that six weeks after ablative surgery was the preferred time to induce CI-AKI. We compared multiple pretreatment plans and found that dehydration for 48 hours before iodixanol (320, 10 mL/kg) administration was optimal to induce CI-AKI in the 5/6 NE rats. Compared with iodixanol, iohexol induced a significantly greater reduction in renal function, severe renal tissue damage, intrarenal hypoxia, and apoptotic tubular cells. Iohexol and iodixanol resulted in similarly marked increases in levels of inflammation and oxidative stress. In summary, the 5/6 NE rat combined with dehydration for 48 hours is a useful pretreatment to establish a novel and reliable CI-AKI model. Iohexol induced more severe CI-AKI than iodixanol in this model.
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China ; Division of Nephrology, The Affiliated Changzhou No. 2 Hospital of Nanjing Medical College, Changzhou, Jiangsu 213003, China.
authors.forename: Tong-qiang
authors.initials: TQ
authors.lastname: Liu
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Wei-li
authors.initials: WL
authors.lastname: Luo
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Tan
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China ; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China ; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China.
authors.forename: Xiao-fang
authors.initials: XF
authors.lastname: Yu
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Jie-ru
authors.initials: JR
authors.lastname: Cai
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China ; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China.
authors.forename: Xiao-qiang
authors.initials: XQ
authors.lastname: Ding
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000652:urine; D000818:Animals; D003287:Contrast Media / Q000633:toxicity*; D004195:Disease Models, Animal; D007472:Iohexol / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D008297:Male; D009392:Nephrectomy / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014283:Triiodobenzoic Acids / Q000633:toxicity*
chemical_list: D003287:Contrast Media; D014283:Triiodobenzoic Acids; D007472:Iohexol; C044834:iodixanol