title: Simultaneous Determination of Five Specific and Sensitive Nephrotoxicity Biomarkers in Serum and Urine Samples of Four Drug-Induced Kidney Injury Models.
abstract: In clinical diagnosis, serum creatinine (CR) was commonly used as the routine markers for the evaluation of kidney injury. To investigate the specific and sensitive nephrotoxicity biomarkers in different drug-induced kidney injury (DKI) models, receiver operating characteristic (ROC) analysis was applied in this study. The quantification data were acquired by the LC-MS determination. Histopathology results showed that different kinds of kidney injuries were observed in different DKI models (gentamycin, cisplatin, methotrexate and amphotericin B models), indicating the injuries might be caused by different mechanisms. Then, five typical biomarkers were simultaneously determined by a newly developed and validated LC-MS method. Uric acid, CR, hippuric acid, 3-indoxyl sulfate and phenaceturic acid were separated by an Apollo C18column and a methanol/water (5 mM ammonium acetate) gradient program. The prepared calibration curves showed good linearity with regression coefficients all above 0.9927. Of all the analytes, the precision were below 9.9% and the accuracy were from -10.3% to 9.2%. ROC results showed that different nephrotoxicity biomarkers were specific in different DKI models. The changes of different biomarkers might be induced by different nephrotoxic mechanisms in the DKI models. These specific and sensitive biomarkers in combination with serum CR are promising in the clinical diagnosis of DKI.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Gu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Biochemistry and Molecular Genetics, Stem Cell Institute, University of Alabama at Birmingham, 777 Shelby interdisciplinary biomedical building, 1825 university boulevard, Birmingham, AL 35294-2182, USA.
authors.forename: Ruowen
authors.initials: R
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wei
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Kai-Shun
authors.initials: KS
authors.lastname: Bi
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China cxh_syphu@hotmail.com.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Chen
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000139:chemically induced / Q000652:urine*; D000818:Animals; D015415:Biomarkers / Q000097:blood* / Q000652:urine*; D003404:Creatinine; D005998:Glycine / Q000031:analogs & derivatives; D006626:Hippurates; D007200:Indican; D007668:Kidney / Q000737:chemistry / Q000473:pathology; D016014:Linear Models; D008297:Male; D012372:ROC Curve; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014527:Uric Acid
chemical_list: D015415:Biomarkers; D006626:Hippurates; D014527:Uric Acid; C022050:phenylacetylglycine; D003404:Creatinine; D007200:Indican; C030514:hippuric acid; D005998:Glycine