Plasma Levels of Fibroblast Growth Factor 21 and Adverse Kidney Outcomes

To investigate the association between fibroblast growth factor 21 (FGF21) and adverse kidney outcomes.

From the prospective observational cohort study using data from the UK Biobank between March 13, 2006, and August 31, 2017, a total of 32,281 individuals with estimated glomerular filtration rate of 60 mL/min per 1.73 m² and higher and urine albumin to creatinine ratio below 30 mg/g (cohort 1) and 3339 individuals with estimated glomerular filtration rate below 60 mL/min per 1.73 m² or urine albumin to creatinine ratio of 30 mg/g and higher (cohort 2), all with baseline plasma FGF21 measurements, were included. The primary predictor was plasma FGF21 levels measured by proximity extension assay. The primary outcomes were incident chronic kidney disease (CKD) for cohort 1 and incident kidney failure requiring replacement therapy (KFRT) for cohort 2.

In cohort 1, 804 (5.6%) participants experienced the CKD outcome during a median 13.7 years of follow-up. A cause-specific competing model revealed adjusted hazard ratios with 95% CIs of 1.01 (0.88 to 1.17), 1.01 (0.87 to 1.17), and 1.25 (1.08 to 1.44) for Q2 to Q4 compared with Q1 (P_trend=.002). In cohort 2, 83 (2.5%) participants had KFRT during a median 13.7 years of follow-up. Elevated FGF21 levels were similarly associated with a higher KFRT risk, with adjusted hazard ratios of 2.79 (0.97 to 8.05), 3.91 (1.44 to 10.66), and 3.81 (1.44 to 10.08) for Q2 to Q4 (P_trend=.01). Subgroup analysis revealed stronger association in non-CKD participants with obesity and dyslipidemia, whereas for CKD participants, this association was stronger in those with increased inflammatory markers.

Higher FGF21 levels correlated with heightened risks of adverse kidney outcomes in individuals with and without CKD. However, the metabolic abnormalities potentially influencing this association varied according to baseline kidney function.