title: Assessment of cell-cycle arrest biomarkers to predict early and delayed acute kidney injury.
abstract: OBJECTIVE
  To assess urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor binding protein 7 ([TIMP-2]·[IGFBP7]), urinary neutrophil gelatinase-associated lipocalin (NGAL), and urinary cystatin-C as acute kidney injury predictors (AKI) exploring the association of nonrenal factors with elevated biomarker levels.
  
  
  METHODS
  We studied 94 patients with urine collected within 48 hours of ICU admission and no AKI at sampling. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria. Predictive performance was assessed by the area under the receiver operating characteristics (ROC) curve. Associations between biomarkers and clinical factors were assessed by multivariate linear regression.
  
  
  RESULTS
  Overall, 19 patients (20%) developed AKI within 48 hours. [TIMP-2]·[IGFBP7], NGAL, or cystatin-C admission levels did not differ between patients without AKI and patients developing AKI. [TIMP-2]·[IGFBP7], NGAL, and cystatin-C were poor AKI predictors (ROC areas 0.34-0.51). Diabetes was independently associated with higher [TIMP-2]·[IGFBP7] levels (P = 0.02) but AKI was not (P = 0.24). Sepsis was independently associated with higher NGAL (P < 0.001) and cystatin-C (P = 0.003) levels.
  
  
  CONCLUSIONS
  Urinary [TIMP-2]·[IGFBP7], NGAL, and cystatin-C should be used cautiously as AKI predictors in general ICU patients since urine levels of these biomarkers are affected by factors other than AKI and their performance can be poor.
authors: Section of Anaesthesia and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, 17176 Stockholm, Sweden.
authors: Max
authors: M
authors: Bell
authors: Clinical Chemistry, Department of Medical Sciences, Uppsala University, 751 85 Uppsala, Sweden.
authors: Anders
authors: A
authors: Larsson
authors: Clinical Chemistry, Department of Medical Sciences, Uppsala University, 751 85 Uppsala, Sweden.
authors: Per
authors: P
authors: Venge
authors: Department of Intensive Care, Austin Hospital, Heidelberg, Melbourne, VIC 3084, Australia ; Australian and New Zealand Intensive Care Research Centre, School of Preventive Medicine and Public Health, Monash University, Melbourne, VIC 3800, Australia.
authors: Rinaldo
authors: R
authors: Bellomo
authors: Section of Anaesthesia and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, 17176 Stockholm, Sweden ; Department of Intensive Care, Austin Hospital, Heidelberg, Melbourne, VIC 3084, Australia.
authors: Johan
authors: J
authors: Mårtensson
mesh_terms: D058186:Acute Kidney Injury / Q000652:urine*; D000209:Acute-Phase Proteins / Q000652:urine*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D059447:Cell Cycle Checkpoints; D055316:Cystatin C / Q000652:urine*; D005260:Female; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000652:urine*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000652:urine*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000652:urine*
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D055316:Cystatin C; D018969:Insulin-Like Growth Factor Binding Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; C102529:insulin-like growth factor binding protein-related protein 1; D019716:Tissue Inhibitor of Metalloproteinase-2