Identification of IGFBP-7 by urinary proteomics as a novel prognostic marker in early acute kidney injury.
Early diagnosis of acute kidney injury (AKI) and accurate prognostic stratification is a prerequisite for optimal medical management. To identify novel prognostic markers of AKI, urine was collected on the first day of AKI in critically ill patients. Twelve patients with early recovery and 12 matching patients with late/non-recovery were selected and their proteome analyzed by gel electrophoresis and mass spectrometry. We identified eight prognostic candidates including α-1 microglobulin, α-1 antitrypsin, apolipoprotein D, calreticulin, cathepsin D, CD59, insulin-like growth factor-binding protein 7 (IGFBP-7), and neutrophil gelatinase-associated lipocalin (NGAL). Subsequent quantification by ELISA showed that IGFBP-7 was the most potent predictor of renal recovery. IGFBP-7 and NGAL were then chosen for further analyses in an independent verification group of 28 patients with and 12 control patients without AKI. IGFBP-7 and NGAL discriminated between early and late/non-recovery patients and patients with and without AKI. Significant upregulation of the urinary markers predicted mortality (IGFBP-7: AUC 0.68; NGAL: AUC 0.81), recovery (IGFBP-7: AUC 0.74; NGAL: AUC 0.70), and severity of AKI (IGFBP-7: AUC 0.77; NGAL: AUC 0.69), and were associated with the duration of AKI. IGFBP-7 was a more accurate predictor of renal outcome than NGAL. Thus, IGFBP-7 is a novel prognostic urinary marker that warrants further investigation.
1] Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany [2] Department of Nephrology/Hypertension, Inselspital, University of Bern, Bern, Switzerland.
Fabienne
F
Aregger
Department of Nephrology/Hypertension, Inselspital, University of Bern, Bern, Switzerland.
Dominik E
DE
Uehlinger
Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
Janusz
J
Witowski
Functional Genomics Center Zurich, Zurich, Switzerland.
René A
RA
Brunisholz
Functional Genomics Center Zurich, Zurich, Switzerland.
Peter
P
Hunziker
Department of Nephrology/Hypertension, Inselspital, University of Bern, Bern, Switzerland.
Felix J
FJ
Frey
Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
Achim
A
Jörres
D058186:Acute Kidney Injury / Q000652:urine*; D000209:Acute-Phase Proteins / Q000652:urine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; 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; D009391:Nephelometry and Turbidimetry; D011379:Prognosis; D040901:Proteomics; D011518:Proto-Oncogene Proteins / Q000652:urine; D057825:Two-Dimensional Difference Gel Electrophoresis
D000209:Acute-Phase Proteins; D015415:Biomarkers; 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