Document Detail

Proteomic identification of early biomarkers of acute kidney injury after cardiac surgery in children.
MedLine Citation:
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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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
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 
Date Detail:
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    
Other Details:
Languages:  eng     Pagination:  632-42     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Acute Kidney Injury / diagnosis*,  etiology
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
Case-Control Studies
Child, Preschool
Creatinine / blood*
Early Diagnosis
Follow-Up Studies
Heart Defects, Congenital / diagnosis,  surgery
Logistic Models
Multivariate Analysis
Postoperative Complications / diagnosis,  epidemiology
Predictive Value of Tests
Prospective Studies
Proteomics / methods*
Risk Assessment
Sensitivity and Specificity
Severity of Illness Index
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods
Grant Support
Reg. No./Substance:
0/Acute-Phase Proteins; 0/Alpha-Globulins; 0/Biological Markers; 0/alpha-1-microglobulin; AYI8EX34EU/Creatinine
Comment In:
Am J Kidney Dis. 2011 Jun;57(6):960; author reply 960-1   [PMID:  21601130 ]
Am J Kidney Dis. 2010 Oct;56(4):609-11   [PMID:  20851316 ]

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