The FGF23-Klotho axis promotes microinflammation in chronic kidney disease

Cytokine. 2024 Dec:184:156781. doi: 10.1016/j.cyto.2024.156781. Epub 2024 Oct 24.

Abstract

The management of chronic kidney disease (CKD) is a global health challenge. Elevated levels of inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), are associated with higher mortality rates in patients with CKD. Moreover, increased fibroblast growth factor 23 (FGF23) levels are a strong predictor of adverse clinical outcomes in CKD. The production of Klotho, which plays a protective role is decreased in patients with CKD. However, the relationship between FGF23-Klotho and levels of inflammatory factors in patients with CKD is unclear. This study aimed to explore the effects of changes in the FGF23-Klotho axis on inflammatory factors in patients with CKD, with a view to providing ideas for novel treatments of CKD. Clinical data were collected from 85 patients with CKD and 17 healthy subjects admitted to the Department of Nephrology of Henan Provincial People's Hospital between June-August 2023. The differences in biochemical indicators at various stages of CKD and healthy people were analyzed. Using enzyme-linked immunosorbent assay and immunohistochemistry, changes in the FGF23-Klotho axis, and their relationship with interleukin 6 (IL-6) and TNF-α were assessed. FGF23 levels gradually increased from CKD stages 1 to 5, with significant differences observed between stages 3 to 5. Klotho levels significantly decreased in CKD stages 3-5. The levels of C-reactive protein (CRP), IL-6, and TNF-α gradually increased. Overall, FGF23 expression was negatively correlated with Klotho levels and positively correlated with CRP, IL-6, and TNF-α levels. In renal tubular epithelial cells, knockdown of Klotho and overexpression of FGF23 increased the expression of inflammatory factors; however, their levels were significantly lower than that of the Klotho knockdown group. Collectively, these findings demonstrate that in CKD, the FGF23-Klotho axis promotes the expression of inflammatory cytokines in renal tubular epithelial cells.

Keywords: Chronic kidney disease; FGF23; Inflammatory; Klotho.

MeSH terms

  • Adult
  • Aged
  • Female
  • Fibroblast Growth Factor-23* / metabolism
  • Fibroblast Growth Factors* / metabolism
  • Glucuronidase* / metabolism
  • Humans
  • Inflammation* / metabolism
  • Interleukin-6* / metabolism
  • Klotho Proteins* / metabolism
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic* / metabolism
  • Tumor Necrosis Factor-alpha* / metabolism

Substances

  • Klotho Proteins
  • Fibroblast Growth Factor-23
  • FGF23 protein, human
  • Fibroblast Growth Factors
  • Interleukin-6
  • Glucuronidase
  • Tumor Necrosis Factor-alpha
  • KL protein, human