Document Detail


Netrin-1 and kidney injury. II. Netrin-1 is an early biomarker of acute kidney injury.
MedLine Citation:
PMID:  18234954     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acute kidney injury is an important complication in hospitalized patients often diagnosed late and associated with high mortality and morbidity. Although biomarkers for nephrotoxicity are available, they often lack sensitivity and specificity for detecting tubular injury. Netrin-1 is a laminin-like molecule highly expressed in many organs including kidney. To determine the value of netrin-1 as a biomarker of renal injury, we analyzed its urinary excretion following ischemia-reperfusion-, cisplatin-, folic acid-, and endotoxin-induced renal injury in mice. Urinary netrin-1 levels increased markedly within 3 h of ischemia-reperfusion (40 +/- 14-fold, P < 0.01 vs. baseline), reached a peak level at 6 h, and decreased thereafter, returning to near baseline by 72 h. Serum creatinine significantly increased only after 24 h of reperfusion. Similarly, in cisplatin-, folic acid-, and lipopolysaccharide-treated mice, urine netrin-1 excretion increased as early as 1 h and reached a peak level at 6 h after injection. However, serum creatinine was raised significantly after 6, 24, and 72 h after folic acid, lipopolysaccharide, and cisplatin administration, respectively. NGAL excretion in folic acid- and lipopolysaccharide-treated mice urine samples could only be detected by 24 h after drug administration. Furthermore, urinary netrin-1 excretion increased dramatically in 13 acute renal failure patients, whereas none was detected in 6 healthy volunteer urine samples. Immunohistochemical localization showed that netrin-1 is highly expressed in tubular epithelial cells in transplanted human kidney. We conclude that urinary netrin-1 is a promising early biomarker of renal injury.
Authors:
W Brian Reeves; Osun Kwon; Ganesan Ramesh
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-01-30
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  294     ISSN:  1931-857X     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-04-03     Completed Date:  2008-06-13     Revised Date:  2011-04-28    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F731-8     Citation Subset:  IM    
Affiliation:
Division of Nephrology, H040, Pennsylvania State Univ. College of Medicine, 500 Univ. Drive, Hershey, PA 17033, USA.
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MeSH Terms
Descriptor/Qualifier:
Acute Kidney Injury / chemically induced,  diagnosis*
Acute-Phase Proteins
Animals
Biological Markers / analysis
Cisplatin / therapeutic use
Creatinine / blood
Humans
Kidney / injuries*
Kidney Diseases / diagnosis*
Lipocalins / blood
Lipopolysaccharides / toxicity
Male
Mice
Mice, Inbred C57BL
Nerve Growth Factors / urine*
Proto-Oncogene Proteins / blood
Renal Circulation
Reperfusion Injury / chemically induced,  diagnosis
Tumor Suppressor Proteins / urine*
Grant Support
ID/Acronym/Agency:
R01-DK-063120/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Acute-Phase Proteins; 0/Biological Markers; 0/LCN2 protein, human; 0/Lipocalins; 0/Lipopolysaccharides; 0/Nerve Growth Factors; 0/Proto-Oncogene Proteins; 0/Tumor Suppressor Proteins; 15663-27-1/Cisplatin; 158651-98-0/netrin-1; 60-27-5/Creatinine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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