Journal
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Volume 4, Issue 4, Pages 763-771Publisher
AMER SOC NEPHROLOGY
DOI: 10.2215/CJN.0200608
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Funding
- NCCIH NIH HHS [R21 NICAN-AT002278, R21 AT002278] Funding Source: Medline
- NHLBI NIH HHS [R01 HL055605, R01-HL55605-08S1] Funding Source: Medline
- NICHD NIH HHS [R24 HD050846, 5R24 HD050846] Funding Source: Medline
- NIDDK NIH HHS [R01 DK049419, R01-DK049419-10S2] Funding Source: Medline
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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 (it = 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.
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