Serum Fibroblast Growth Factor 21 Is Associated with Renal Function and Chronic Kidney Disease in Community‐Dwelling Adults

To the Editor: Fibroblast growth factor 21 (FGF21) is a recently discovered hormone that is expressed primarily in the liver and stimulates glucose uptake in adipocytes. Circulating FGF21 is high in adults with obesity, metabolic syndrome, diabetes mellitus, and coronary heart disease. In a cohort in Hong Kong, high FGF21 predicted incident diabetes mellitus. FGF21 levels are high in end-stage renal disease. The relationship between FGF21 and renal function and chronic kidney disease (CKD) has not been well characterized in communitydwelling adults. It was hypothesized that serum FGF21 would be found to be independently associated with renal function and CKD. Serum FGF21 and renal function were measured in 744 adults in the Baltimore Longitudinal Study of Aging (BLSA) seen between 2002 and 2007. The BLSA has continuing approval from the institutional review board (IRB) of the MedStar Research Institute. The Institutional Review board of the Johns Hopkins School of Medicine approved the protocol for the present study. Fasting blood samples were collected between 7:00 a.m. and 8:00 a.m. and stored at –80°C until the time of analysis. Serum creatinine was measured using the Jaffe method. Serum FGF21 was measured using an enzyme-linked immunosorbent assay (Quantikine Human FGF-21 ELISA, R & D Systems, Minneapolis, MN) with intraand interassay coefficients of variability of 2.8% and 7.0%, respectively. CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m using the Chronic Kidney Disease Epidemiology Collaboration equation. Multivariable logistic and linear regression models were used to examine the relationship between log serum FGF21 and other factors and CKD and eGFR, respectively. Covariates included in the multivariable models were basic demographic variables (age, sex, race) and variables that were significantly associated with tertiles of serum FGF21. Diabetes mellitus was included in the multivariate models because it is known to be associated with higher FGF21 levels and abnormal glucose metabolism. Overall, the median (25th, 75th percentile) serum FGF21 concentration was 227 (127, 371) pg/mL. Of the 744 adults, 144 (19.3%) had CKD. The characteristics of the participants according to tertile of serum FGF21 are shown in Table 1. Age, sex, race, current smoking, body mass index (BMI), eGFR, and proportion of individuals with hypertension, angina pectoris, congestive heart failure, and CKD were significantly different across tertiles of FGF21. There were no significant differences in diabetes mellitus, myocardial infarction, stroke, and cancer according to tertile of serum FGF21. Log FGF21 (per 1 SD increase [0.77]) was associated with CKD in a multivariable logistic regression model adjusted for age, race, sex, smoking, BMI, and chronic diseases (hypertension, congestive heart failure, angina pectoris, and diabetes mellitus) (odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.03–1.69, P = . 03). Results were similar if diabetes mellitus was excluded from the model (OR = 1.33, 95% CI = 1.04–1.70, P = .02). Log FGF21 (per 1 SD increase) was associated with eGFR in a multivariable linear regression model adjusted for age, race, sex, smoking, BMI, and chronic diseases (hypertension, congestive heart failure, angina pectoris, and diabetes mellitus) (b = 1.47, standard error (SE) = 0.59, P = . 01). Results were similar if diabetes mellitus was excluded from the model (b = 1.48, SE = 0.59, P = .01).