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

Abstract BackgroundBody mass index (BMI), uric acid (UA) diabetes mellitus (DM) and hypertension (HT) are known risk factors of declined kidney function, and are associated with fetuin-A. However, the causal pathways of these associations are unclear. We therefore used cohort data to explore possible causal pathways of fetuin-A and kidney function. MethodologyWe used data of the Electricity Generating Authority of Thailand cohort 2009 (n= 2305). A causal pathway was constructed, which considered fetuin-A as study factor, BMI, UA, DM, and HT as mediators, and eGFR as the outcome. A generalized-structural equation model (GSEM) with 1000-replication bootstrapping was applied to assess the causal effects adjusting for covariates. ResultsThe fetuin-A → eGFR pathway showed a direct association of fetuin-A on eGFR with the coefficient of -0.0072 (95% CI: -0.0119, -0.0025). In addition, the indirect effects of fetuin-A→ BMI → eGFR was also significant with the coefficient of 0.00086 (0.00025, 0.0016; implying that every one unit of BMI increased, resulting from increasing fetuin-A, would significantly increase eGFR 0.00086 (0.00025, 0.0016) mL/min/1.73m2. There was a negative effect of fetuin-A on eGFR through BMI and UA pathway (Fetuin-A→BMI→UA→eGFR ) as well as the HT pathway (Fetuin-A→BMI→HT→eGFR ) with average casual mediation effects (ACME) of -0.00132 (-0.00177, -0.00092) and -0.00139 (-0.00237, -0.00069). Fetuin-AàDMàHTàeGFR was also statistically significant with the ACME of -0.00223 (-0.00535, -0.00066).ConclusionOur study has shed some light on the possible role of fetuin-A in the etiology of declining renal function through the mediatory roles of BMI, UA, DM and HT in the various complex causal pathways leading to declining kidney function in our study cohort. Further studies are however recommended to examine the pathomechanisms involved in the mediational processes of these studied risk factors in the etiology of declining kidney function.