Iron-related proteins: candidate urine biomarkers in childhood HIV-associated renal diseases.
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.


METHODS
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.


CONCLUSIONS
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.
Soler-García
Angel A
AA
Division of Nephrology, Center for Cancer and Immunology Research, Children's Research Institute, NW, Washington, DC 20010, USA.
Johnson
Douglas
D
Hathout
Yetrib
Y
Ray
Patricio E
PE
D016263:AIDS-Associated Nephropathy / Q000473:pathology / Q000652:urine* / Q000821:virology; D000209:Acute-Phase Proteins / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000652:urine; D001706:Biopsy; D001798:Blood Proteins / Q000652:urine*; D016022:Case-Control Studies; D004195:Disease Models, Animal; D015658:HIV Infections / Q000150:complications / Q000473:pathology / Q000652:urine / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D006242:Haptoglobins / Q000652:urine; D006463:Hemolytic-Uremic Syndrome / Q000473:pathology / Q000652:urine* / Q000821:virology; D006466:Hemopexin / Q000652:urine; D006801:Humans; D007501:Iron / Q000652:urine; D007781:Lactoferrin / Q000652:urine; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D011237:Predictive Value of Tests; D011507:Proteinuria / Q000652:urine* / Q000821:virology; D011518:Proto-Oncogene Proteins / Q000652:urine; D051381:Rats; D055647:Rats, Transgenic; D013997:Time Factors; D014168:Transferrin / Q000652:urine
D000209:Acute-Phase Proteins; D015415:Biomarkers; D001798:Blood Proteins; D006242:Haptoglobins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D014168:Transferrin; D006466:Hemopexin; D007501:Iron; D007781:Lactoferrin