title: Association of definition of acute kidney injury by cystatin C rise with biomarkers and clinical outcomes in children undergoing cardiac surgery.
abstract: OBJECTIVE
  Research has identified improved biomarkers of acute kidney injury (AKI). Cystatin C (CysC) is a better glomerular filtration rate marker than serum creatinine (SCr) and may improve AKI definition.
  
  
  OBJECTIVE
  To determine if defining clinical AKI by increases in CysC vs SCr alters associations with biomarkers and clinical outcomes.
  
  
  METHODS
  Three-center prospective cohort study of intensive care units in New Haven, Connecticut, Cincinnati, Ohio, and Montreal, Quebec, Canada. Participants were 287 patients 18 years or younger without preoperative AKI or end-stage renal disease who were undergoing cardiac surgery. The study dates were July 1, 2007, through December 31, 2009.
  
  
  METHODS
  For biomarker vs clinical AKI associations, the exposures were first postoperative (0-6 hours after surgery) urine interleukin 18, neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, and liver fatty acid-binding protein. For clinical AKI outcome associations, the exposure was Kidney Disease: Improving Global Outcomes AKI definition (based on SCr or CysC).
  
  
  METHODS
  Clinical AKI, length of stay, and length of mechanical ventilation. We determined areas under the receiver operating characteristic curve and odds ratios for first postoperative biomarkers to predict AKI.
  
  
  RESULTS
  The SCr-defined vs CysC-defined AKI incidence differed substantially (43.6% vs 20.6%). Percentage agreement was 71% (κ = 0.38); stage 2 or worse AKI percentage agreement was 95%. Interleukin 18 and kidney injury molecule 1 discriminated for CysC-defined AKI better than for SCr-defined AKI. For interleukin 18 and kidney injury molecule 1, the areas under the receiver operating characteristic curve were 0.74 and 0.65, respectively, for CysC-defined AKI, and 0.66 and 0.58, respectively, for SCr-defined AKI. Fifth (vs first) quintile concentrations of both biomarkers were more strongly associated with CysC-defined AKI. For interleukin 18 and kidney injury molecule 1, the odds ratios were 16.19 (95% CI, 3.55-73.93) and 6.93 (95% CI, 1.88-25.59), respectively, for CysC-defined AKI vs 6.60 (95% CI, 2.76-15.76) and 2.04 (95% CI, 0.94-4.38), respectively, for SCr-defined AKI. Neutrophil gelatinase-associated lipocalin and liver fatty acid-binding protein associations with both definitions were similar. The CysC definitions and SCr definitions were similarly associated with clinical outcomes of resource use.
  
  
  CONCLUSIONS
  Compared with the SCr-based definition, the CysC-based definition is more strongly associated with urine interleukin 18 and kidney injury molecule 1 in children undergoing cardiac surgery. Consideration should be made for defining AKI based on CysC in clinical care and future studies.
authors.affiliation: Division of Nephrology, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Zappitelli
authors.affiliation: Department of Pediatrics, Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Jason H
authors.initials: JH
authors.lastname: Greenberg
authors.affiliation: Program of Applied Translational Research, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut4Clinical Epidemiology Research Center, Veterans Affairs Connecticut, West Haven.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Coca
authors.affiliation: Division of Pediatric Cardiology, Lucile Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, California.
authors.forename: Catherine D
authors.initials: CD
authors.lastname: Krawczeski
authors.affiliation: Department of Pediatrics, Maria Fareri Children's Hospital, New York Medical College, Valhalla, New York.
authors.forename: Simon
authors.initials: S
authors.lastname: Li
authors.affiliation: Division of Nephrology, Department of Medicine, University of Western Ontario, London, Ontario, Canada.
authors.forename: Heather R
authors.initials: HR
authors.lastname: Thiessen-Philbrook
authors.affiliation: Department of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bennett
authors.affiliation: Department of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
authors.affiliation: Program of Applied Translational Research, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut4Clinical Epidemiology Research Center, Veterans Affairs Connecticut, West Haven.
authors.forename: Chirag R
authors.initials: CR
authors.lastname: Parikh
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood*; D005260:Female; D006330:Heart Defects, Congenital / Q000097:blood / Q000601:surgery*; D006801:Humans; D007223:Infant; D015278:Intensive Care Units, Pediatric; D008297:Male; D011183:Postoperative Complications / Q000097:blood* / Q000175:diagnosis; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012016:Reference Values; D057170:Translational Research, Biomedical
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D003404:Creatinine
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