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Iron-related proteins: candidate urine biomarkers in childhood HIV-associated renal diseases.
MedLine Citation:
PMID:  19279121     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Because of the risk of performing renal biopsies in children with co-morbid conditions, we carried out this study to identify candidate protein biomarkers in the urine of HIV-infected children with renal disease. Design, setting, participants & measurements: Urine samples from HIV-infected children with biopsy proven HIV-nephropathy (HIVAN; n = 4), HIV-associated Hemolytic Uremic Syndrome (HIV-HUS; n = 2), or no renal disease (n = 3) were analyzed by two-dimensional electrophoresis (2-DE) and proteomic methods. Positive findings were confirmed in HIV-infected children with (n = 20) and without (n = 10) proteinuria using commercially available assays. RESULTS: By 2-DE analysis, a single urine marker was not sufficient to distinguish children with HIVAN from the others. High urine levels of beta(2)-microglobulin and retinol-binding protein (RBP) suggested the presence of tubular injury. In addition, we found elevated urine levels of iron and the iron-related proteins, transferrin, hemopexin, haptoglobin, lactoferrin, and neutrophil gelatinase-associated lipocalin (NGAL), in children with HIVAN and HIV-HUS. Furthermore, we detected a significant accumulation of iron in the urine and kidneys of HIV-transgenic (Tg) rats with renal disease. CONCLUSION: These findings suggest that iron and iron-related proteins might be promising candidate urine biomarkers to identify HIV-infected children at risk of developing HIVAN and HIV-HUS. Moreover, based on the results of previous studies, we speculate that the release or accumulation of iron in the kidney of HIV-infected children may contribute to the rapid progression of their renal disease, and could become a new therapeutic target against HIVAN and HIV-HUS.
Authors:
Angel A Soler-García; Douglas Johnson; Yetrib Hathout; Patricio E Ray
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-03-11
Journal Detail:
Title:  Clinical journal of the American Society of Nephrology : CJASN     Volume:  4     ISSN:  1555-905X     ISO Abbreviation:  Clin J Am Soc Nephrol     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-06     Completed Date:  2009-06-08     Revised Date:  2010-09-22    
Medline Journal Info:
Nlm Unique ID:  101271570     Medline TA:  Clin J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  763-71     Citation Subset:  IM    
Affiliation:
Division of Nephrology, Center for Cancer and Immunology Research, Children's Research Institute, NW, Washington, DC 20010, USA.
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MeSH Terms
Descriptor/Qualifier:
AIDS-Associated Nephropathy / pathology,  urine*,  virology
Acute-Phase Proteins / urine
Animals
Biological Markers / urine
Biopsy
Blood Proteins / urine*
Case-Control Studies
Disease Models, Animal
HIV Infections / complications,  pathology,  urine,  virology*
HIV-1 / genetics,  pathogenicity*
Haptoglobins / urine
Hemolytic-Uremic Syndrome / pathology,  urine*,  virology
Hemopexin / urine
Humans
Iron / urine
Lactoferrin / urine
Lipocalins / urine
Predictive Value of Tests
Proteinuria / urine*,  virology
Proto-Oncogene Proteins / urine
Rats
Rats, Transgenic
Time Factors
Transferrin / urine
Grant Support
ID/Acronym/Agency:
5R24 HD050846/HD/NICHD NIH HHS; R01-DK049419-10S2/DK/NIDDK NIH HHS; R01-HL55605-08S1/HL/NHLBI NIH HHS; R21 NICAN-AT002278/AT/NCCAM NIH HHS
Chemical
Reg. No./Substance:
0/Acute-Phase Proteins; 0/Biological Markers; 0/Blood Proteins; 0/Haptoglobins; 0/LCN2 protein, human; 0/Lactoferrin; 0/Lipocalins; 0/Proto-Oncogene Proteins; 11096-37-0/Transferrin; 7439-89-6/Iron; 9013-71-2/Hemopexin
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