title: Tissue Inhibitor Metalloproteinase-2 (TIMP-2)⋅IGF-Binding Protein-7 (IGFBP7) Levels Are Associated with Adverse Long-Term Outcomes in Patients with AKI.
abstract: Tissue inhibitor metalloproteinase-2 (TIMP-2) and IGF-binding protein-7 (IGFBP7) have been validated for risk stratification in AKI. However, the association of urinary TIMP-2 and IGFBP7 with long-term outcomes is unknown. We evaluated the 9-month incidence of a composite end point of all-cause mortality or the need for RRT in a secondary analysis of a prospective observational international study of critically ill adults. Two predefined [TIMP-2]⋅[IGFBP7] cutoffs (0.3 for high sensitivity and 2.0 for high specificity) for the development of AKI were evaluated. Cox proportional hazards models were used to determine risk for the composite end point. Baseline [TIMP-2]⋅[IGFBP7] values were available for 692 subjects, of whom 382 (55.2%) subjects developed stage 1 AKI (defined by Kidney Disease Improving Global Outcomes guidelines) within 72 hours of enrollment and 217 (31.4%) subjects met the composite end point. Univariate analysis showed that [TIMP-2]⋅[IGFBP7]>2.0 was associated with increased risk of the composite end point (hazard ratio [HR], 2.11; 95% confidence interval [95% CI], 1.37 to 3.23; P<0.001). In a multivariate analysis adjusted for the clinical model, [TIMP-2]⋅[IGFBP7] levels>0.3 were associated with death or RRT only in subjects who developed AKI (compared with levels≤0.3: HR, 1.44; 95% CI, 1.00 to 2.06 for levels>0.3 to ≤2.0; P=0.05 and HR, 2.16; 95% CI, 1.32 to 3.53 for levels>2.0; P=0.002). In conclusion, [TIMP-2]⋅[IGFBP7] measured early in the setting of critical illness may identify patients with AKI at increased risk for mortality or receipt of RRT over the next 9 months.
authors.affiliation: Section of Nephrology, Department of Medicine, University of Chicago, Chicago, Illinois;
authors.forename: Jay L
authors.initials: JL
authors.lastname: Koyner
authors.affiliation: Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee;
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Shaw
authors.affiliation: Department of Medicine, Divisions of Intensive Care Medicine and Nephrology, Washington DC Veterans Affairs Medical Center, Washington DC;
authors.forename: Lakhmir S
authors.initials: LS
authors.lastname: Chawla
authors.affiliation: Department of Intensive Care Medicine, Ghent University Hospital, Ghent University, Ghent, Belgium;
authors.forename: Eric A J
authors.initials: EA
authors.lastname: Hoste
authors.affiliation: Department of Anesthesiology, University of Florida, Gainesville, Florida;
authors.forename: Azra
authors.initials: A
authors.lastname: Bihorac
authors.affiliation: Department of Medicine, Division of Nephrology and Hypertension and Division of Pulmonary Critical Care Medicine, Mayo Clinic, Rochester, Minnesota;
authors.forename: Kianoush
authors.initials: K
authors.lastname: Kashani
authors.affiliation: Department of Nephrology, Hypertension, Diabetes and Endocrinology, Otto von Guericke University, Magdeburg, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Haase
authors.affiliation: Statistics at Walker BioSciences, Carlsbad, California; and.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.affiliation: Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania kellumja@ccm.upmc.edu.
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
mesh_terms: D058186:Acute Kidney Injury / Q000401:mortality* / Q000628:therapy* / Q000652:urine; D000328:Adult; D015415:Biomarkers / Q000652:urine; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000652:urine*; D053208:Kaplan-Meier Estimate; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D006435:Renal Dialysis / Q000379:methods* / Q000401:mortality; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016019:Survival Analysis; D013997:Time Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000652:urine*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D018969:Insulin-Like Growth Factor Binding Proteins; C102529:insulin-like growth factor binding protein-related protein 1; D019716:Tissue Inhibitor of Metalloproteinase-2
keywords: epidemiology and outcomes; kidney; mortality