Document Detail

Mass spectrometry-based proteomic analysis of urine in acute kidney injury following cardiopulmonary bypass: a nested case-control study.
MedLine Citation:
PMID:  19070948     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The early evolution of acute kidney injury (AKI) in humans is difficult to study noninvasively. We hypothesized that urine proteomics could provide insight into the early pathophysiology of human AKI. STUDY DESIGN: A prospective nested case-control study (n = 250) compared serial urinary proteomes of 22 patients with AKI and 22 patients without AKI before, during, and after cardiopulmonary bypass surgery. OUTCOMES: AKI was defined as a greater than 50% increase in serum creatinine level, and non-AKI, as less than 10% increase from baseline. MEASUREMENTS: Serum creatinine, urine protein-creatinine ratio, neutrophil gelatinase-associated lipocalin (NGAL), alpha1-microglobulin, interferon-inducible protein-10 (IP-10), monokine induced by interferon gamma (Mig), interferon-inducible T cell alpha chemoatractant (I-TAC), interleukin 6 (IL-6), IL-1beta, and IL-10. Urine protein profiling by means of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). RESULTS: SELDI-TOF-MS showed intraoperative tubular stress in both groups on arrival to the intensive care unit, evidenced by beta2-microglobulinuria. Non-AKI proteomes returned toward baseline postoperatively. In contrast, AKI proteomes showed a second phase of tubular injury/stress with the reappearance of beta2-microglobulin and multiple unidentified peaks (3 to 5 and 6 to 8 kDa) and the appearance of established tubular injury markers: urinary protein, alpha1-microglobulin, and NGAL. Furthermore, 2 novel peaks (2.43 and 2.78 kDa) were found to be dominant in postoperative non-AKI urine samples. The 2.78-kDa protein was identified as the active 25-amino acid form of hepcidin (hepcidin-25), a key regulator of iron homeostasis. Finally, an inflammatory component of reperfusion injury was evaluated by means of enzyme-linked immunosorbent assay analysis of candidate chemokines (IP-10, I-TAC, and Mig) and cytokines (IL-6, IL-1beta, and IL-10). Of these, IP-10 was upregulated in patients with versus without AKI postoperatively. LIMITATIONS: This is an observational study. SELDI-TOF-MS is a semiquantitative technique. CONCLUSIONS: Evaluation of human AKI revealed early intraoperative tubular stress in all patients. A second phase of injury observed in patients with AKI may involve IP-10 recruitment of inflammatory cells. The enhancement of hepcidin-25 in patients without AKI may suggest a novel role for iron sequestration in modulating AKI.
Julie Ho; Malcolm Lucy; Oleg Krokhin; Kent Hayglass; Edward Pascoe; Gayle Darroch; David Rush; Peter Nickerson; Claudio Rigatto; Martina Reslerova
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-12-13
Journal Detail:
Title:  American journal of kidney diseases : the official journal of the National Kidney Foundation     Volume:  53     ISSN:  1523-6838     ISO Abbreviation:  Am. J. Kidney Dis.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-27     Completed Date:  2009-04-09     Revised Date:  2009-10-27    
Medline Journal Info:
Nlm Unique ID:  8110075     Medline TA:  Am J Kidney Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  584-95     Citation Subset:  IM    
Section of Nephrology, University of Manitoba, Winnipeg, Manitoba, Canada.
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MeSH Terms
Acute-Phase Proteins / urine
Alpha-Globulins / urine
Antimicrobial Cationic Peptides / urine
Biological Markers / blood,  urine
Cardiopulmonary Bypass / adverse effects*
Case-Control Studies
Chemokine CXCL10
Creatinine / blood,  urine
Disease Progression
Glomerular Filtration Rate / physiology
Interleukin-10 / urine
Interleukin-6 / urine
Kidney Failure, Acute / etiology*,  urine*
Lipocalins / urine
Middle Aged
Prospective Studies
Proteomics / methods*
Proto-Oncogene Proteins / urine
Reperfusion Injury / etiology*,  urine*
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization*
beta 2-Microglobulin / urine
Reg. No./Substance:
0/Acute-Phase Proteins; 0/Alpha-Globulins; 0/Antimicrobial Cationic Peptides; 0/Biological Markers; 0/CXCL10 protein, human; 0/Chemokine CXCL10; 0/Interleukin-6; 0/LCN2 protein, human; 0/Lipocalins; 0/Proto-Oncogene Proteins; 0/beta 2-Microglobulin; 0/hepcidin; 130068-27-8/Interleukin-10; 60-27-5/Creatinine
Comment In:
Am J Kidney Dis. 2009 Nov;54(5):979; author reply 980   [PMID:  19853199 ]
Am J Kidney Dis. 2009 Apr;53(4):569-71   [PMID:  19324244 ]

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