title: Evaluation of clinically available renal biomarkers in critically ill adults: a prospective multicenter observational study.
abstract: BACKGROUND
  Although serum cystatin C (sCysC), urinary N-acetyl-β-D-glucosaminidase (uNAG), and urinary albumin/creatinine ratio (uACR) are clinically available, their optimal combination for acute kidney injury (AKI) detection and prognosis prediction remains unclear. We aimed to assess the discriminative abilities of these biomarkers and their possible combinations for AKI detection and intensive care unit (ICU) mortality prediction in critically ill adults.
  
  
  METHODS
  A multicenter, prospective observational study was conducted in mixed medical-surgical ICUs at three tertiary care hospitals. One thousand eighty-four adult critically ill patients admitted to the ICUs were studied. We assessed the use of individual biomarkers (sCysC, uNAG, and uACR) measured at ICU admission and their combinations with regard to AKI detection and prognosis prediction.
  
  
  RESULTS
  AUC-ROCs for sCysC, uNAG, and uACR were calculated for total AKI (0.738, 0.650, and 0.683, respectively), severe AKI (0.839, 0.706, and 0.771, respectively), and ICU mortality (0.727, 0.793, and 0.777, respectively). The panel of sCysC plus uNAG detected total and severe AKI with significantly higher accuracy than either individual biomarkers or the other two panels (uNAG plus uACR or sCysC plus uACR). For detecting total AKI, severe AKI, and ICU mortality at ICU admission, this panel yielded AUC-ROCs of 0.756, 0.863, and 0.811, respectively; positive predictive values of 0.71, 0.31, and 0.17, respectively; and negative predictive values of 0.81, 0.97, and 0.98, respectively. Moreover, this panel significantly contributed to the accuracy of the clinical models for AKI detection and ICU mortality prediction, as measured by the AUC-ROC, continuous net reclassification index, and incremental discrimination improvement index. The comparable performance of this panel was further confirmed with bootstrap internal validation.
  
  
  CONCLUSIONS
  The combination of a functional marker (sCysC) and a tubular damage marker (uNAG) revealed significantly superior discriminative performance for AKI detection and yielded additional prognostic information on ICU mortality.
authors.affiliation: Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, People's Republic of China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Critical Care Medicine, Xiaolan Hospital of Southern Medical University, 65 Jucheng Road, Zhongshan, 528415, Guangdong, People's Republic of China.
authors.forename: Ruibin
authors.initials: R
authors.lastname: Chi
authors.affiliation: Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, People's Republic of China.
authors.forename: Shenglong
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Critical Care Medicine, Guangzhou Nansha Central Hospital, 105 Fengzhe Road, Nansha, 511400, Guangdong, People's Republic of China.
authors.forename: Heng
authors.initials: H
authors.lastname: Ye
authors.affiliation: Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, People's Republic of China.
authors.forename: Yiling
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, People's Republic of China.
authors.forename: Danqing
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, People's Republic of China.
authors.forename: Linhui
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Lv
authors.affiliation: Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Long
authors.affiliation: Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, People's Republic of China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Sun
authors.affiliation: National Clinical Research Center for Kidney Disease, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Road, Guangzhou, 510515, Guangdong, People's Republic of China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Public Health, Sun Yat-sen University, 74 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, People's Republic of China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zou
authors.affiliation: Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, People's Republic of China. gghccm@163.com.
authors.forename: Chunbo
authors.initials: C
authors.lastname: Chen
mesh_terms: D000118:Acetylglucosaminidase / Q000032:analysis; D058186:Acute Kidney Injury / Q000175:diagnosis*; D000328:Adult; D015415:Biomarkers / Q000032:analysis* / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000032:analysis / Q000652:urine; D016638:Critical Illness / Q000628:therapy*; D055316:Cystatin C / Q000032:analysis / Q000097:blood; D005260:Female; D006801:Humans; D007362:Intensive Care Units / Q000458:organization & administration; D007668:Kidney / Q000293:injuries; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D012079:Renal Circulation / Q000502:physiology; D000075462:Serum Albumin, Human / Q000032:analysis / Q000652:urine
chemical_list: D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D003404:Creatinine; D000118:Acetylglucosaminidase; D000075462:Serum Albumin, Human
keywords: Acute kidney injury; Intensive care unit; N-acetyl-β-D-glucosaminidase; Renal biomarker; Serum cystatin C; Urinary albumin/creatinine ratio