Causal association pathways between fetuin-A and kidney function: a mediation analysis

Objective: Body mass index (BMI), uric acid, diabetes mellitus, and hypertension are risk factors for reduced kidney function and are associated with fetuin-A levels, but their causal pathways remain unclear. The objective of this study was to investigate this knowledge gap. Methods: A repeated cross-sectional design was used to assess causal pathway effects of fetuinA on the estimated glomerular filtration rate (eGFR), which is mediated through BMI, uric acid, diabetes mellitus, and hypertension. Results: Among 2305 participants, the mean eGFR at baseline decreased from 98.7±23.6 mL/minute/1.73 m2 in 2009 to 92.4±22.9 mL/minute/1.73 m2 in 2014. Fetuin-A was significantly associated with eGFR, suggesting that increasing fetuin-A levels predict a decrease in eGFR. Additionally, the indirect effect of fetuin-A on eGFR, as assessed through BMI, was also significant. The effects of fetuin-A on eGFR through other mediation pathways showed variable results. Conclusions: Our study revealed a possible role of fetuin-A in the etiology of declining renal function through mediating body mass index, uric acid, diabetes mellitus, and hypertension via complex causal pathways. Further studies to clarify these mediated effects are recommended.