Differential renal proteomics analysis in a novel rat model of iodinated contrast-induced acute kidney injury
Ying-Hao Deng,
Xiu-Fen Wang,
Xi Wu,
Ping Yan,
Qian Liu,
Ting Wu,
Shao-Bin Duan
Affiliations
Ying-Hao Deng
Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital of Central South University Changsha, Hunan, P.R. China
Xiu-Fen Wang
Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital of Central South University Changsha, Hunan, P.R. China
Xi Wu
Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital of Central South University Changsha, Hunan, P.R. China
Ping Yan
Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital of Central South University Changsha, Hunan, P.R. China
Qian Liu
Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital of Central South University Changsha, Hunan, P.R. China
Ting Wu
Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital of Central South University Changsha, Hunan, P.R. China
Shao-Bin Duan
Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital of Central South University Changsha, Hunan, P.R. China
AbstractContrast-induced acute kidney injury (CI-AKI), which occurs after the use of iodinated contrast media, has become the third leading cause of hospital-acquired acute kidney injury (AKI). It is associated with prolonged hospitalization and increased risks of end-stage renal disease and mortality. The pathogenesis of CI-AKI is unclear and effective treatments are lacking. By comparing different post-nephrectomy times and dehydration times, we constructed a new, short-course CI-AKI model using dehydration for 24 h two weeks after unilateral nephrectomy. We found that the low-osmolality contrast media iohexol caused more severe renal function decline, renal morphological damage, and mitochondrial ultrastructural alterations compared to the iso-osmolality contrast media iodixanol. The shotgun proteomics based on Tandem Mass Tag (TMT) was used to conduct proteomics research on renal tissue in the new CI-AKI model, and 604 distinct proteins were identified, mainly involving complement and coagulation cascade, COVID-19, PPAR signalling pathway, mineral absorption, cholesterol metabolism, ferroptosis, staphylococcus aureus infection, systemic lupus erythematosus, folate biosynthesis, and proximal tubule bicarbonate reclamation. Then, using parallel reaction monitoring (PRM), we validate 16 candidate proteins, of which five were novel candidates (Serpina1, Apoa1, F2, Plg, Hrg) previously unrelated to AKI and associated with an acute response as well as fibrinolysis. The pathway analysis and 16 candidate proteins may help to discover new mechanisms in the pathogenesis of CI-AKI, allowing for early diagnosis and outcome prediction.
