title: Common chronic conditions do not affect performance of cell cycle arrest biomarkers for risk stratification of acute kidney injury.
abstract: Identification of acute kidney injury (AKI) can be challenging in patients with underlying chronic disease, and biomarkers often perform poorly in this population. In this study we examined the performance characteristics of the novel biomarker panel of urinary tissue inhibitor of metalloproteinases-2 (TIMP2) and insulin-like growth factor-binding protein 7 ([IGFBP7]) in patients with a variety of comorbid conditions.
  
  
  
  We analyzed data from two multicenter studies of critically ill patients in which [TIMP2]•[IGFBP7] was validated for prediction of Kidney Disease: Improving Global Outcomes (KDIGO) Stage 2 or 3 AKI within 12 h. We constructed receiver operating characteristic (ROC) curves for AKI prediction both overall and by comorbid conditions common among patients with AKI, including diabetes mellitus, congestive heart failure (CHF) and chronic kidney disease (CKD).
  
  
  
  In the overall cohort of 1131 patients, 139 (12.3%) developed KDIGO Stage 2 or 3 AKI. [TIMP2]•[IGFBP7] was significantly higher in AKI versus non-AKI patients, both overall and within each comorbidity subgroup. The AUC for [TIMP2]•[IGFBP7] in predicting AKI was 0.81 overall. Higher AUC was noted in patients with versus without CHF (0.89 versus 0.79; P = 0.026) and CKD (0.91 versus 0.80; P = 0.024).
  
  
  
  We observed no significant impairment in the performance of cell cycle arrest biomarkers due to the presence of chronic comorbid conditions.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Heung
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Allegheny General Hospital, Pittsburgh, PA, USA.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Ortega
authors.affiliation: Department of Anesthesia and Medicine, George Washington University, Washington, DC, USA.
authors.forename: Lakhmir S
authors.initials: LS
authors.lastname: Chawla
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Wunderink
authors.affiliation: Department of Emergency Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Wesley H
authors.initials: WH
authors.lastname: Self
authors.affiliation: Section of Nephrology, Department of Medicine, University of Chicago, Chicago, IL, USA.
authors.forename: Jay L
authors.initials: JL
authors.lastname: Koyner
authors.affiliation: Walker Bioscience, Carlsbad, CA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.affiliation: Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002908:Chronic Disease; D016638:Critical Illness; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D018570:Risk Assessment
chemical_list: D015415:Biomarkers; D018797:Cell Cycle Proteins
keywords: acute kidney injury; biomarkers; chronic kidney disease