Iron-Related Proteins

Abstract

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 HIVnephropathy (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 HIVinfected 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 ␤ 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.

Urinary Hepcidin-25 and Risk of Acute Kidney Injury Following Cardiopulmonary Bypass

“…Furthermore, the upregulation of heme-oxygenase 1 suggests that iron trafficking and homeostasis plays a key role in renal IRI (23). The role of labile iron in potentiating renal injury may not be unique to IRI, as several iron-binding proteins have been detected in the urinary samples of children with human immunodeficiency virus nephropathy and urinary hepcidin-25 appears to be associated with renal relapse in lupus nephritis (24,25). This raises the possibility of a common renal injury pathway involving iron and iron-binding proteins.…”

Neutrophil Gelatinase-Associated Lipocalin (NGAL) as a New Biomarker for Non – Acute Kidney Injury (AKI) Diseases

“…Nephrosis and a quick decline in kidney function characterize HIV-associated nephropathy and HIVassociated uremic syndrome. Urinary NGAL levels, in two independent studies, were found to be significantly higher in these HIV-associated renal diseases than in HIV-positive and HIV-negative patients with other forms of chronic kidney disorders [24,25]. IgA nephropathy (IgAN) is the most common form of glomerulonephritis.…”

Quantitative mass spectrometry of urinary biomarkers

“…This approach was successfully used for identification of potential biomarkers of different renal diseases. High urinary levels of β2-microglobulin, retinol-binding protein, transferrin, hemopexin, haptoglobin, lactoferrin, and neutrophil gelatinase-associated lipocalin (NGAL) were identified as candidate biomarkers for HIV-associated nephropathy [40]. Retinol-binding protein was also identified as a candidate biomarker for acute tubular necrosis [41].…”