title: Identification of nestin as a urinary biomarker for acute kidney injury.
abstract: OBJECTIVE
  Acute kidney injury (AKI) is a common complication in hospitalized patients and the incidence of AKI is rapidly increasing. Despite the advances in treatment of AKI, many patients still progress to end-stage renal disease and depend on dialysis. Therefore, early diagnosis and adequate treatment of AKI could improve prognosis.
  
  
  METHODS
  We established rat models of AKI induced by cisplatin nephrotoxicity and renal ischemia-reperfusion (I/R). Urine samples were collected, labeled with isobaric tags for relative and absolute quantification agents, and then subjected to nano-LC-MS/MS-based proteomic analysis. Results of the proteomic study were confirmed by Western blot. We also performed RNAi to silence nestin and investigate its role in renal I/R injury. We then validated its clinical application by studying urine nestin levels in AKI patients with cardiovascular surgeries.
  
  
  RESULTS
  Our proteomic analysis showed that fetuin-A, nestin, hamartin and T-kininogen were differentially expressed in the urine samples of rats after cisplatin or I/R treatment. Western blot confirmed the differential expression of these proteins in animal models and ELISA confirmed the differential expression of nestin in human urine samples. To explore the expression of nestin in the development of AKI, our results showed that nestin was primarily detected in the glomeruli and barely detected in tubular cells but increased in tubular cells during I/R- and cisplatin-induced AKI. The urine nestin-to-creatinine ratio increased earlier than serum creatinine in AKI patients with postcardiovascular surgeries. The role of nestin in AKI might be related to the p53 signaling pathway.
  
  
  CONCLUSIONS
  Thus, our results demonstrated that urinary nestin could be a urinary biomarker for patients with AKI and its role in AKI might be related to the p53 signaling pathway.
authors: Department of Nephrology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China.
authors: Wen
authors: W
authors: Zhang
authors: Lu
authors: L
authors: Zhang
authors: Yong-Xi
authors: YX
authors: Chen
authors: Yin-Yin
authors: YY
authors: Xie
authors: Yan-Fang
authors: YF
authors: Zou
authors: Ming-Jun
authors: MJ
authors: Zhang
authors: Yao-Hui
authors: YH
authors: Gao
authors: Yue
authors: Y
authors: Liu
authors: Qiang
authors: Q
authors: Zhao
authors: Qiu-Hua
authors: QH
authors: Huang
authors: Nan
authors: N
authors: Chen
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000175:diagnosis* / Q000652:urine*; D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015415:Biomarkers / Q000652:urine; D002945:Cisplatin / Q000494:pharmacology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D064231:Nestin / Q000235:genetics / Q000652:urine*; D011183:Postoperative Complications / Q000175:diagnosis* / Q000652:urine*; D040901:Proteomics / Q000379:methods; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000502:physiology; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; C577484:NES protein, human; C577486:Nes protein, rat; D064231:Nestin; D034741:RNA, Small Interfering; D002945:Cisplatin