Associations of FGF23 with 10-Year Change in eGFR and UACR and with Incident CKD in the CARDIA Cohort

KEY POINTS: FGF23 has a nonlinear positive association with incident CKD among healthy, middle-aged adults. The relationship between FGF23 and incident CKD was only significant among participants with cFGF23 levels in the highest quartile. FGF23 is not associated with 10-year change in eGFR or 10-year change in UACR among healthy, middle-aged adults. BACKGROUND: The relationship of fibroblast growth factor 23 (FGF23) with incident CKD has been examined in older but not younger populations. METHODS: Linear regression models were used to examine the associations of c-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) with 10-year change (1995–96 to 2005–06) in eGFR and urine albumin-to-creatinine ratio (UACR) in the Coronary Artery Risk Development in Young Adults cohort. Cox proportional hazard models were used to assess the association of cFGF23 with incident CKD, defined as eGFR <60 ml/min per 1.73 m(2) or UACR ≥30 mg/g. Multivariable models were adjusted for age, sex, race, education, field center, physical activity, body mass index, diabetes, smoking, and systolic BP. RESULTS: Among 2511 participants, the mean age was 45±3.6 years; mean eGFR was 96.5±14.0 ml/min per 1.73 m(2); and median UACR was 4.3 (interquartile range, 3.0–6.7) mg/g. Most (62.6%) participants were nonsmokers; the prevalence of diabetes was low (6.6%); and median values for 10-year changes in eGFR and UACR were modest (−5.50 ml/min per 1.73 m(2) and 0.70 mg/g, respectively). No consistent associations between cFGF23 and 10-year change in eGFR and UACR were observed. During a median follow-up of 9.98 years, incident CKD developed in 258 participants. There was a nonlinear association of cFGF23 with incident CKD, and relative to the lowest quartile of cFGF23, a significant relationship was detected only among participants in the highest quartile (hazard ratio, 1.58; 95% confidence interval, 1.09 to 2.27). Similar findings were observed for iFGF23. CONCLUSION: Among middle-aged adults in the Coronary Artery Risk Development in Young Adults cohort, median eGFR and UACR changes were modest and cFGF23 and iFGF23 were not consistently associated with 10-year change in eGFR or UACR. A nonlinear relationship was observed between cFGF23 and incident CKD, with individuals with highest cFGF23 levels being at risk of developing CKD.