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

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Abstract

Background

Children living with HIV frequently show high plasma levels of fibroblast growth factor-2 (FGF-2/bFGF). FGF-2 accelerates the progression of several experimental kidney diseases; however, the role of circulating FGF-2 in childhood HIV-chronic kidney diseases (HIV-CKDs) is unknown. We carried out this study to determine whether high plasma FGF-2 levels were associated with the development of HIV-CKDs in children.

Methods

The plasma and urine FGF-2 levels were measured in 84 children (< 12 years of age) living with HIV during the pre-modern antiretroviral era, and followed for at least 3 years to determine the prevalence of proteinuria and HIV-CKDs. We also assessed the distribution of the kidney FGF-2 binding sites by autoradiography and Alcian blue staining, and explored potential mechanisms by which circulating FGF-2 may precipitate HIV-CKDs in cultured kidney epithelial and mononuclear cells derived from children with HIV-CKDs.

Results

High plasma FGF-2 levels were associated with a high viral load. Thirteen children (~ 15%) developed HIV-CKDs and showed a large reservoir of FGF-2 low-affinity binding sites in the kidney, which can facilitate the recruitment of circulating FGF-2. Children with high plasma and urine FGF-2 levels had 73-fold increased odds (95% CI 9–791) of having HIV-CKDs relative to those with normal FGF-2 values. FGF-2 induced the proliferation and decreased the expression of APOL-1 mRNA in podocytes, and increased the attachment and survival of infected mononuclear cells cultured from children with HIV-CKDs.

Conclusions

High plasma FGF-2 levels appear to be an additional risk factor for developing progressive childhood HIV-CKDs.

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Data availability

All data generated or analyzed during this study are included in this published article and its Supplementary information files.

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Funding

This study was supported by the National Institutes of Health awards R01 DK-103564; R01 DK-108368; R01 DK-115968; and R01 DK-04941.

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Authors and Affiliations

  1. Child Health Research Center, Department of Pediatrics, School of Medicine, University of Virginia, Room 2120, MR4 Building, 409 Lane Road, Charlottesville, VA, 22908, USA

    Patricio E. Ray & Jing Yu

  2. Center for Genetic Medicine Research, Children’s National Hospital, Washington, DC, USA

    Jinliang Li & Jharna R. Das

  3. Department of Pediatrics, The George Washington University School of Medicine, Washington, DC, USA

    Jinliang Li & Jharna R. Das

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  1. Patricio E. Ray
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  2. Jinliang Li
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Correspondence to Patricio E. Ray.

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A previous non-peer-reviewed version of this article was posted as a preprint in medRXiv. doi: https://doi.org/10.1101/2020.12.08.20246280.

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Ray, P.E., Li, J., Das, J. et al. Association of circulating fibroblast growth factor-2 with progression of HIV-chronic kidney diseases in children. Pediatr Nephrol 36, 3933–3944 (2021). https://doi.org/10.1007/s00467-021-05075-y

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