|Proteomic identification of early biomarkers of acute kidney injury after cardiac surgery in children.|
|PMID: 20599305 Owner: NLM Status: MEDLINE|
|BACKGROUND: Serum creatinine is a delayed marker of acute kidney injury (AKI). Our purpose is to discover and validate novel early urinary biomarkers of AKI after cardiac surgery.
STUDY DESIGN: Diagnostic test study.
SETTING & PARTICIPANTS: Children undergoing cardiopulmonary bypass surgery. The test set included 15 participants with AKI and 15 matched controls (median age, 1.5 year) of 45 participants without AKI. The validation set included 365 children (median age, 1.9 year).
INDEX TESTS: Biomarkers identified using proteomic profiling: α(1)-microglobulin, α(1)-acid glycoprotein, and albumin.
REFERENCE TEST: AKI, defined as ≥50% increase in serum creatinine level from baseline within 3 days of surgery.
RESULTS: Proteomic profiling using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) showed 3 protein peaks that appeared consistently within 2 hours in children who developed AKI after cardiopulmonary bypass surgery. The proteins were identified as α(1)-microglobulin, α(1)-acid glycoprotein, and albumin. Using clinical assays, results were confirmed in a test set and validated in an independent prospective cohort. In the validation set, 135 (37%) developed AKI, in whom there was a progressive increase in urinary biomarker concentrations with severity of AKI. Areas under the curve for urinary α(1)-microglobulin, α(1)-acid glycoprotein, and albumin at 6 hours after cardiac surgery were 0.84 (95% CI, 0.79-0.89), 0.87 (95% CI, 0.83-0.91), and 0.76 (95% CI, 0.71-0.81), respectively. Participants with increasing quartiles of biomarkers showed increasing lengths of hospital stays and durations of AKI (P < 0.001).
LIMITATIONS: Single-center study of children with normal kidney function at recruitment. The SELDI-TOF MS technique has limited sensitivity for the detection of proteins greater than the 20-kDa range.
CONCLUSIONS: Urinary α(1)-microglobulin, α(1)-acid glycoprotein, and albumin represent early, accurate, inexpensive, and widely available biomarkers of AKI after cardiac surgery. They also offer prognostic information about the duration of AKI and length of hospitalization after cardiac surgery.
|Prasad Devarajan; Catherine D Krawczeski; Mai T Nguyen; Thelma Kathman; Zhu Wang; Chirag R Parikh|
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|Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't|
|Title: American journal of kidney diseases : the official journal of the National Kidney Foundation Volume: 56 ISSN: 1523-6838 ISO Abbreviation: Am. J. Kidney Dis. Publication Date: 2010 Oct|
|Created Date: 2010-09-20 Completed Date: 2010-10-13 Revised Date: 2014-09-18|
Medline Journal Info:
|Nlm Unique ID: 8110075 Medline TA: Am J Kidney Dis Country: United States|
|Languages: eng Pagination: 632-42 Citation Subset: IM|
|Copyright © 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.|
|APA/MLA Format Download EndNote Download BibTex|
Acute Kidney Injury
Acute-Phase Proteins / urine*
Alpha-Globulins / urine*
Analysis of Variance
Biological Markers / analysis, metabolism
Cardiac Surgical Procedures / adverse effects, methods
Cardiopulmonary Bypass / adverse effects*, methods
Creatinine / blood*
Heart Defects, Congenital / diagnosis, surgery
Postoperative Complications / diagnosis, epidemiology
Predictive Value of Tests
Proteomics / methods*
Sensitivity and Specificity
Severity of Illness Index
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods
|R01 DK069749/DK/NIDDK NIH HHS; R01 DK069749/DK/NIDDK NIH HHS; R01 HL085757/HL/NHLBI NIH HHS; R01 HL085757/HL/NHLBI NIH HHS; R01 HL08676/HL/NHLBI NIH HHS|
|0/Acute-Phase Proteins; 0/Alpha-Globulins; 0/Biological Markers; 0/alpha-1-microglobulin; AYI8EX34EU/Creatinine|
Am J Kidney Dis. 2011 Jun;57(6):960; author reply 960-1
Am J Kidney Dis. 2010 Oct;56(4):609-11 [PMID: 20851316 ]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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