title: Test characteristics of urinary biomarkers depend on quantitation method in acute kidney injury.
abstract: The concentration of urine influences the concentration of urinary biomarkers of AKI. Whether normalization to urinary creatinine concentration, as commonly performed to quantitate albuminuria, is the best method to account for variations in urinary biomarker concentration among patients in the intensive care unit is unknown. Here, we compared the diagnostic and prognostic performance of three methods of biomarker quantitation: absolute concentration, biomarker normalized to urinary creatinine concentration, and biomarker excretion rate. We measured urinary concentrations of alkaline phosphatase, γ-glutamyl transpeptidase, cystatin C, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and IL-18 in 528 patients on admission and after 12 and 24 hours. Absolute concentration best diagnosed AKI on admission, but normalized concentrations best predicted death, dialysis, or subsequent development of AKI. Excretion rate on admission did not diagnose or predict outcomes better than either absolute or normalized concentration. Estimated 24-hour biomarker excretion associated with AKI severity, and for neutrophil gelatinase-associated lipocalin and cystatin C, with poorer survival. In summary, normalization to urinary creatinine concentration improves the prediction of incipient AKI and outcome but provides no advantage in diagnosing established AKI. The ideal method for quantitating biomarkers of urinary AKI depends on the outcome of interest.
authors.affiliation: Christchurch Kidney Research Group, Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Azrina Md
authors.initials: AM
authors.lastname: Ralib
authors.forename: John W
authors.initials: JW
authors.lastname: Pickering
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
authors.forename: Charles L
authors.initials: CL
authors.lastname: Edelstein
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Bonventre
authors.forename: Zoltan H
authors.initials: ZH
authors.lastname: Endre
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000652:urine; D000209:Acute-Phase Proteins / Q000652:urine; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000652:urine*; D055316:Cystatin C / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D020382:Interleukin-18 / Q000652:urine; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000652:urine; D005723:gamma-Glutamyltransferase / Q000652:urine
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D020382:Interleukin-18; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D005723:gamma-Glutamyltransferase
references.citation: Kidney Int. 2010 Sep;78(5):486-94
references.pmid: 20555318
references.citation: Kidney Int. 2005 Jun;67(6):2089-100
references.pmid: 15882252
references.citation: Crit Care Med. 2003 Apr;31(4):1250-6
references.pmid: 12682500
references.citation: Am J Clin Nutr. 1983 Mar;37(3):478-94
references.pmid: 6829490
references.citation: Cytokine. 2000 Oct;12(10):1526-30
references.pmid: 11023668
references.citation: Nephrol Dial Transplant. 2003 Mar;18(3):543-51
references.pmid: 12584277
references.citation: Clin J Am Soc Nephrol. 2007 May;2(3):431-9
references.pmid: 17699448
references.citation: Pediatr Nephrol. 2011 Feb;26(2):267-74
references.pmid: 20978799
references.citation: Clin Chem. 1992 Oct;38(10):1933-53
references.pmid: 1394976
references.citation: Crit Care. 2007;11(2):R31
references.pmid: 17331245
references.citation: Ann Intern Med. 2008 Jun 3;148(11):810-9
references.pmid: 18519927
references.citation: Kidney Int. 2010 Sep;78(5):433-5
references.pmid: 20706215
references.citation: Crit Care. 2007;11(4):R84
references.pmid: 17678545
references.citation: Intensive Care Med. 2010 Aug;36(8):1333-40
references.pmid: 20397003
references.citation: JAMA. 2005 Aug 17;294(7):813-8
references.pmid: 16106006
references.citation: Am J Kidney Dis. 2008 Sep;52(3):595-605
references.pmid: 18725016
references.citation: J Clin Pharmacol. 1976 Jul;16(7):321-8
references.pmid: 947964
references.citation: J Clin Invest. 2005 Mar;115(3):610-21
references.pmid: 15711640
references.citation: Kidney Int. 2011 May;79(10):1119-30
references.pmid: 21307838
references.citation: Clin Transl Sci. 2008 Dec;1(3):200-8
references.pmid: 19212447
references.citation: J Am Soc Nephrol. 2007 Mar;18(3):904-12
references.pmid: 17267747
references.citation: Nephrol Dial Transplant. 2012 Oct;27 Suppl 3:iii96-103
references.pmid: 21551085
references.citation: Intensive Care Med. 2010 Mar;36(3):452-61
references.pmid: 19956924
references.citation: Kidney Int. 2010 Jun;77(11):1020-30
references.pmid: 20164823
references.citation: Clin J Am Soc Nephrol. 2008 May;3(3):665-73
references.pmid: 18337554
references.citation: Crit Care. 2010;14(3):R85
references.pmid: 20459852
references.citation: Ann Thorac Surg. 2010 Oct;90(4):1142-8
references.pmid: 20868804
references.citation: Radiology. 1982 Apr;143(1):29-36
references.pmid: 7063747
references.citation: Crit Care Med. 2009 Jan;37(1):96-104
references.pmid: 19050610
references.citation: Lancet. 2005 Apr 2-8;365(9466):1231-8
references.pmid: 15811456
references.citation: Clin J Am Soc Nephrol. 2009 Nov;4(11):1705-15
references.pmid: 19729431
references.citation: Kidney Int. 1985 Jun;27(6):928-37
references.pmid: 4021321
references.citation: Crit Care. 2004 Aug;8(4):R204-12
references.pmid: 15312219
references.citation: Shock. 2001 Dec;16(6):411-4
references.pmid: 11770036
references.citation: J Am Soc Nephrol. 2007 Feb;18(2):407-13
references.pmid: 17229907
references.citation: Clin J Am Soc Nephrol. 2010 Jul;5(7):1165-73
references.pmid: 20498242
references.citation: Kidney Int. 2010 Nov;78(9):926-33
references.pmid: 20686452
references.citation: Biometrics. 1988 Sep;44(3):837-45
references.pmid: 3203132
references.citation: Nephrol Dial Transplant. 2008 Feb;23(2):566-72
references.pmid: 17911094
references.citation: Nephrol Dial Transplant. 2010 Jun;25(6):1833-9
references.pmid: 20054022
references.citation: Clin J Am Soc Nephrol. 2010 Aug;5(8):1497-505
references.pmid: 20558561