1. Association of circulating fibroblast growth factor-2 with progression of HIV-chronic kidney diseases in children
- Author
-
Jinliang Li, Jharna R. Das, Jing Yu, and Patricio E. Ray
- Subjects
Nephrology ,medicine.medical_specialty ,Human immunodeficiency virus (HIV) ,030232 urology & nephrology ,HIV Infections ,Urine ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Kidney ,Fibroblast growth factor ,Peripheral blood mononuclear cell ,Article ,03 medical and health sciences ,0302 clinical medicine ,Chronic Kidney Diseases ,Internal medicine ,medicine ,Humans ,Renal Insufficiency, Chronic ,Risk factor ,Fibroblast ,Child ,Messenger RNA ,Proteinuria ,business.industry ,medicine.disease ,Endocrinology ,medicine.anatomical_structure ,HIV-associated nephropathy ,Pediatrics, Perinatology and Child Health ,Disease Progression ,Fibroblast Growth Factor 2 ,medicine.symptom ,business ,Viral load - Abstract
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.
- Published
- 2021