epidermal-growth-factor and AIDS-Associated-Nephropathy

Human immunodeficiency virus (HIV)-infected children are at risk of developing several types of renal diseases, including HIV-associated nephropathy (HIVAN), which is usually seen during late stages of infection in children with a high viral load. This disease is defined by the presence of proteinuria associated with mesangial hyperplasia and/or global-focal segmental glomerulosclerosis combined with microcystic transformation of the renal tubules. Because HIVAN can have an insidious clinical onset, renal biopsy is the only definitive way of establishing a diagnosis. Given the risk of performing this procedure in HIV-infected children with other AIDS-defining illness, we sought to identify informative biomarkers such as growth factors in the urine of 55 HIV-infected children that might be predictive of the extent and activity of the renal lesions characteristic of HIVAN. We found that the levels of epidermal growth factor were lower in the urine of children with renal disease, whereas levels of fibroblast growth factor-2 and metalloproteinase-2 were higher as compared with those levels in infected children without renal disease. Similar changes were observed in HIV-Tg26 mice correlating with the progression of renal disease in this model of HIVAN. Our findings suggest that this urinary growth factor profile may be useful in facilitating the diagnosis of HIV-infected children at risk of developing HIVAN when interpreted in the appropriate clinical setting.

Topics: Adolescent; AIDS-Associated Nephropathy; Animals; Biomarkers; Case-Control Studies; Child; Child, Preschool; Epidermal Growth Factor; Fibroblast Growth Factor 2; HIV Infections; Humans; Infant; Intercellular Signaling Peptides and Proteins; Matrix Metalloproteinase 2; Mice; Mice, Transgenic; Predictive Value of Tests; Viral Load

Soler-García and collaborators show that changing levels of urinary biomarkers associated with the pathology of HIV-associated nephropathy may identify HIV-infected children at greatest risk for this complication. These changes appear relatively early in disease progression and remain responsive to antiviral therapy. Will these trends be borne out in a multicenter study?

Topics: AIDS-Associated Nephropathy; Biomarkers; Epidermal Growth Factor; Fibroblast Growth Factor 2; Humans; Matrix Metalloproteinase 2