Urinary biomarkers in the clinical prognosis and early detection of acute kidney injury.
OBJECTIVE
Several novel urinary biomarkers have shown promise in the early detection and diagnostic evaluation of acute kidney injury (AKI). Clinicians have limited tools to determine which patients will progress to more severe forms of AKI at the time of serum creatinine increase. The diagnostic and prognostic utility of novel and traditional AKI biomarkers was evaluated during a prospective study of 123 adults undergoing cardiac surgery.


METHODS
Urinary neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CyC), kidney injury molecule-1 (KIM-1), hepatocyte growth factor (HGF), π-glutathione-S-transferase (π-GST), α-GST, and fractional excretions of sodium and urea were all measured at preoperative baseline, postoperatively, and at the time of the initial clinical diagnosis of AKI. Receiver operator characteristic curves were generated and the areas under the curve (AUCs) were compared.


RESULTS
Forty-six (37.4%) subjects developed AKI Network stage 1 AKI; 9 (7.3%) of whom progressed to stage 3. Preoperative KIM-1 and α-GST were able to predict the future development of stage 1 and stage 3 AKI. Urine CyC at intensive care unit (ICU) arrival best detected early stage 1 AKI (AUC = 0.70, P < 0.001); the 6-hour ICU NGAL (AUC = 0.88; P < 0.001) best detected early stage 3 AKI. π-GST best predicted the progression to stage 3 AKI at the time of creatinine increase (AUC = 0.86; P = 0.002).


CONCLUSIONS
Urinary biomarkers may improve the ability to detect early AKI and determine the clinical prognosis of AKI at the time of diagnosis.
Koyner
Jay L
JL
Section of Nephrology, Department of Medicine, University of Chicago, Chicago, Illinois, USA.
Vaidya
Vishal S
VS
Bennett
Michael R
MR
Ma
Qing
Q
Worcester
Elaine
E
Akhter
Shahab A
SA
Raman
Jai
J
Jeevanandam
Valluvan
V
O'Connor
Micheal F
MF
Devarajan
Prasad
P
Bonventre
Joseph V
JV
Murray
Patrick T
PT
D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000652:urine; D000209:Acute-Phase Proteins / Q000652:urine; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000652:urine*; D055316:Cystatin C / Q000652:urine; D042241:Early Diagnosis; D005260:Female; D005982:Glutathione Transferase / Q000652:urine; D000072596:Hepatitis A Virus Cellular Receptor 1; D017228:Hepatocyte Growth Factor / Q000652:urine; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine; D012372:ROC Curve; D011991:Receptors, Virus
D000209:Acute-Phase Proteins; D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus; D017228:Hepatocyte Growth Factor; D005982:Glutathione Transferase
Clin Transl Sci. 2008 Dec;1(3):200-8
19212447
Thorac Cardiovasc Surg. 2009 Apr;57(3):125-9
19330747
Kidney Int. 2008 Oct;74(8):1059-69
18650797
Am J Kidney Dis. 2007 Oct;50(4):566-73
17900456
Thorac Cardiovasc Surg. 1993 Aug;41(4):237-41
8211928
Biomarkers. 2009 Sep;14(6):423-31
19572801
Kidney Int. 2002 Jul;62(1):237-44
12081583
Crit Care. 2008;12(4):R96
18673539
J Clin Pathol. 1989 Jun;42(6):624-8
2738168
JAMA. 2007 Apr 25;297(16):1801-9
17456822
Ann Intern Med. 1998 Feb 1;128(3):194-203
9454527
J Thorac Cardiovasc Surg. 1979 Jun;77(6):880-8
439924
Clin J Am Soc Nephrol. 2009 May;4(5):873-82
19406962
J Am Soc Nephrol. 2010 Jan;21(1):189-97
19762491
Curr Opin Crit Care. 2004 Dec;10(6):476-82
15616389
Ren Fail. 2004 Jul;26(4):385-92
15462106
Kidney Int. 2006 Jul;70(1):199-203
16710348
Nephrol Dial Transplant. 1999 May;14(5):1158-62
10344355
J Thorac Cardiovasc Surg. 1994 Jun;107(6):1489-95
8196394
Clin J Am Soc Nephrol. 2010 Feb;5(2):211-9
20056755
Intensive Care Med. 2000 May;26(5):565-71
10923731
Am J Transplant. 2006 Jul;6(7):1639-45
16827865
Crit Care Med. 2009 Feb;37(2):553-60
19114878
Clin Chem. 2004 Mar;50(3):552-8
14709451
Anesthesiology. 2006 Sep;105(3):485-91
16931980
Am J Med. 1984 Oct;77(4):699-702
6486145
Clin J Am Soc Nephrol. 2008 Nov;3(6):1615-9
18784207
Crit Care Med. 2008 Apr;36(4 Suppl):S159-65
18382188
Am J Kidney Dis. 2003 Jan;41(1):76-83
12500223
Ann Intern Med. 1999 Mar 16;130(6):461-70
10075613
Nephrol Dial Transplant. 2003 Mar;18(3):543-51
12584277
Ann Thorac Surg. 2009 Jul;88(1):124-30
19559209
J Am Soc Nephrol. 2003 Oct;14(10):2534-43
14514731
Crit Care. 2007;11(2):R31
17331245
Lancet. 2005 Apr 2-8;365(9466):1231-8
15811456
Clin J Am Soc Nephrol. 2009 Nov;4(11):1705-15
19729431
Kidney Int. 2008 May;73(9):1008-16
18094679
Crit Care. 2007;11(4):R84
17678545
Clin Biochem. 2010 Apr;43(6):615-20
20026020
Kidney Int. 2004 Sep;66(3):1115-22
15327406
Am J Med. 1998 Apr;104(4):343-8
9576407
Crit Care. 2004 Aug;8(4):R204-12
15312219
Biometrics. 1988 Sep;44(3):837-45
3203132
Kidney Int. 2008 Apr;73(7):863-9
18059454
Pediatr Nephrol. 2009 Dec;24(12):2409-12
19756765
J Thorac Cardiovasc Surg. 1976 Mar;71(3):323-33
1249963