Circulating fibroblast growth factor 21 links hemodynamics with kidney function in middle-aged and older adults: A mediation analysis.

Altered hemodynamics are commonly observed in individuals with declining renal function; however, the pathophysiological mechanisms linking renal dysfunction and hemodynamics have not been fully elucidated. Fibroblast growth factor 21 (FGF21), which upregulates sympathetic nerve activity, can alter systemic hemodynamics, and its level can increase as renal function declines. This study aimed to determine the associations among circulating FGF21 levels, hemodynamics, and renal function in middle-aged and older adults. In a total of 272 middle-aged and older adults (age range: 46-83 years), estimated glomerular filtration rate (eGFR), hemodynamics (brachial and aortic blood pressure and aortic pulse wave velocity [PWV]), and serum FGF21 levels were measured. For mediation analysis, hemodynamic parameters were entered as outcomes. eGFR or log-transformed urinary albumin and creatinine ratio (UACR) and log-transformed serum FGF21 levels were set as the predictors and mediator, respectively. According to multivariable regression models after adjusting for potential covariates, serum FGF21 levels were significantly associated with brachial systolic blood pressure (β = 0.140), pulse pressure (β = 0.136), and aortic PWV (β = 0.144). Mediation analyses showed that serum FGF21 levels significantly mediated the relationship of eGFR with brachial systolic blood pressure (indirect effect [95% confidence interval]: -0.032 [-0.071, -0.002]), pulse pressure (-0.019 [-0.041, -0.001]), and aortic PWV (-0.457 [-1.053, -0.021]) and the relationship of UACR with aortic PWV (7.600 [0.011, 21.148]). These findings suggest that elevated circulating FGF21 levels partially mediate the association of elevated blood pressure and/or aortic stiffness with renal dysfunction in middle-aged and older adults.