Urinary Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) • Insulin-Like Growth Factor-Binding Protein 7 (IGFBP7) Predicts Adverse Outcome in Pediatric Acute Kidney Injury

• Published in: PloS one 2015-11, Vol.10 (11), p.e0143628
• Main Authors: Westhoff, Jens H, Tönshoff, Burkhard, Waldherr, Sina, Pöschl, Johannes, Teufel, Ulrike, Westhoff, Timm H, Fichtner, Alexander
• Format: Article
• Language: English
• Subjects: Acute kidney failure; Acute Kidney Injury - diagnosis; Acute Kidney Injury - etiology; Acute Kidney Injury - mortality; Acute Kidney Injury - urine; Adolescent; Age Factors; Asphyxia; Binding; Biomarkers; Care and treatment; Case-Control Studies; Cell cycle; Child; Child, Preschool; Children; Complications and side effects; Criteria; Dehydration; Diagnostic systems; Epidemiology; Etiology; Female; Health risks; Hospitals; Humans; Hypertension; Hypovolemia; Illnesses; Immunoassay; Infant; Infant, Newborn; Influence; Inhibitors; Injuries; Insulin; Insulin-Like Growth Factor Binding Proteins - urine; Insulin-like growth factors; Intensive care units; Kaplan-Meier Estimate; Kidney diseases; Kidney transplantation; Kidneys; Male; Metalloproteinase; Metalloproteins; Mortality; Neonates; Nephritis; Newborn babies; Patient Outcome Assessment; Patients; Pediatrics; Performance prediction; Prognosis; Prospective Studies; Proteins; Risk factors; ROC Curve; Rodents; Senescence; Septic shock; Services; Stability; Studies; Taiwan; Thromboembolism; Thrombosis; Tissue inhibitor of metalloproteinase 2; Tissue Inhibitor of Metalloproteinase-2 - urine; Vasculitis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0143628

The G1 cell cycle inhibitors tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as promising biomarkers for the prediction of adverse outcomes including renal replacement therapy (RRT) and mortality in critically ill adult patients who develop acute kidney injury (AKI). However, the prognostic value of urinary TIMP-2 and IGFBP7 in neonatal and pediatric AKI for adverse outcome has not been investigated yet. The product of the urinary concentration of TIMP-2 and IGFBP7 ([TIMP-2]•[IGFBP7]) was assessed by a commercially available immunoassay (NephroCheck™) in a prospective cohort study in 133 subjects aged 0-18 years including 46 patients with established AKI according to pRIFLE criteria, 27 patients without AKI (non-AKI group I) and 60 apparently healthy neonates and children (non-AKI group II). AKI etiologies were: dehydration/hypovolemia (n = 7), hemodynamic instability (n = 7), perinatal asphyxia (n = 9), septic shock (n = 7), typical hemolytic-uremic syndrome (HUS; n = 5), interstitial nephritis (n = 5), vasculitis (n = 4), nephrotoxic injury (n = 1) and renal vein thrombosis (n = 1). When AKI patients were classified into pRIFLE criteria, 6/46 (13%) patients fulfilled the criteria for the category "Risk", 13/46 (28%) for "Injury", 26/46 (57%) for "Failure" and 1/46 (2%) for "Loss". Patients in the "Failure" stage had a median 3.7-fold higher urinary [TIMP-2]•[IGFBP7] compared to non-AKI subjects (P