title: Identification of candidate serum biomarkers for severe septic shock-associated kidney injury via microarray.
abstract: BACKGROUND
  Septic-shock-associated acute kidney injury (SSAKI) carries high morbidity in the pediatric population. Effective treatment strategies are lacking, in part due to poor detection and prediction. There is a need to identify novel candidate biomarkers of SSAKI. The objective of our study was to determine whether microarray data from children with septic shock could be used to derive a panel of candidate biomarkers for predicting SSAKI.
  
  
  METHODS
  A retrospective cohort study compared microarray data representing the first 24 hours of admission for 179 children with septic shock with those of 53 age-matched normal controls. SSAKI was defined as a >200% increase of baseline serum creatinine, persistent to 7 days after admission.
  
  
  RESULTS
  Patients with SSAKI (n = 31) and patients without SSAKI (n = 148) were clinically similar, but SSAKI carried a higher mortality (45% vs. 10%). Twenty-one unique gene probes were upregulated in SSAKI patients versus patients without SSAKI. Using leave-one-out cross-validation and class prediction modeling, these probes predicted SSAKI with a sensitivity of 98% (95% confidence interval (CI) = 81 to 100) and a specificity of 80% (95% CI = 72 to 86). Serum protein levels of two specific genes showed high sensitivity for predicting SSAKI: matrix metalloproteinase-8 (89%, 95% CI = 64 to 98) and elastase-2 (83%, 95% CI = 58 to 96). Both biomarkers carried a negative predictive value of 95%. When applied to a validation cohort, although both biomarkers carried low specificity (matrix metalloproteinase-8: 41%, 95% CI = 28 to 50; and elastase-2: 49%, 95% CI = 36 to 62), they carried high sensitivity (100%, 95% CI = 68 to 100 for both).
  
  
  CONCLUSIONS
  Gene probes upregulated in critically ill pediatric patients with septic shock may allow for the identification of novel candidate serum biomarkers for SSAKI prediction.
authors.affiliation: Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45223, USA.
authors.forename: Rajit K
authors.initials: RK
authors.lastname: Basu
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Standage
authors.forename: Natalie Z
authors.initials: NZ
authors.lastname: Cvijanovich
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Allen
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Thomas
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Freishtat
authors.forename: Nick
authors.initials: N
authors.lastname: Anas
authors.forename: Keith
authors.initials: K
authors.lastname: Meyer
authors.forename: Paul A
authors.initials: PA
authors.lastname: Checchia
authors.forename: Richard
authors.initials: R
authors.lastname: Lin
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Shanley
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bigham
authors.forename: Derek S
authors.initials: DS
authors.lastname: Wheeler
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Goldstein
authors.forename: Hector R
authors.initials: HR
authors.lastname: Wong
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D019272:Leukocyte Elastase / Q000097:blood / Q000235:genetics; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000097:blood / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012772:Shock, Septic / Q000097:blood* / Q000150:complications
chemical_list: D015415:Biomarkers; D019272:Leukocyte Elastase; D020784:Matrix Metalloproteinase 8
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