Association of circulating fibroblast growth factor-2 with progression of HIV-chronic kidney diseases in children

IntroductionPeople living with HIV frequently show high plasma levels of Fibroblast Growth Factor-2 (FGF-2/bFGF). Previous studies reported that FGF-2 can accelerate the progression of experimental kidney diseases. However, how circulating FGF-2 affects the progression of HIV-chronic kidney diseases (HIV-CKDs) in children is unknown.MethodsTo address this question we measured the plasma and urine levels of FGF-2 in 84 children (< 12 years of age) living with HIV, and determine their association with a high viral load (HVL) and HIV-CKDs. Kidney sections from children with HIV-CKD were used to assess the localization and expression levels of the FGF-2 binding sites. The fate of circulating FGF-2 was determined in young wild type and HIV-transgenic (HIV-Tg26) mice injected with human recombinant FGF-2. Cells cultured from children with HIV-CKDs where used to define how FGF-2 affected their infection, survival, and expression of APOL1.ResultsHigh plasma FGF-2 levels were associated with a HVL and HIV-CKDs. High urine FGF-2 levels were found in almost all children with HIV-CKDs. A large reservoir of renal FGF-2 low affinity binding sites in children and HIV-Tg26mice with HIV-CKDs facilitated the recruitment of circulating FGF-2. FGF-2 slightly decreased the expression of APOL1 mRNA in cultured podocytes, but increased the survival of HIV infected inflammatory cells or podocytes, and precipitated HIV-nephropathy in HIV-Tg26mice.ConclusionChildren with high plasma and urine FGF-2 levels were more likely to develop HIV-CKDs. Persistently high plasma FGF-2 levels appear to be an independent risk factor for developing progressive childhood HIV-CKDs.