Fractional excretion of phosphorus modifies the association between fibroblast growth factor-23 and outcomes

Abstract

Fibroblast growth factor-23 (FGF23) induces phosphaturia through its effects on renal tubules. Higher levels of FGF23 associate with cardiovascular disease (CVD) events and all-cause mortality, but it is unknown whether these associations differ by the degree of phosphaturia. Here, we measured serumFGF23 and 24-hour urine fractional excretion of phosphorus (FePi) in 872 outpatients with stable CVD and a mean estimated GFR of 71 ml/min per 1.73 m2. During an average 7.5 years of follow-up, there were 337 deaths and 199 CVD events. Urinary FePi significantly modified the association of FGF23 with each outcome (P interaction<0.001 for all-causemortality and P interaction<0.05 forCVD events). Inmodels adjusted for CVD risk factors, kidney function, and PTH, those patients who had FGF23 above the median (≥42.3 relative units [RU]/ml) but FePi belowthemedian (<15.7%) had the highest risks of both all-causemortality (HR=1.98, 95% CI=1.42-2.77) and CVD events (HR=1.92, 95% CI=1.25-2.94) compared with those patients who had low concentrations of FGF23 and low FePi. In summary, associations of FGF23 with mortality andCVDevents are stronger in personswith lower FePi independent of PTHand kidney function. In such individuals, the renal tubular response to FGF23 may be suboptimal. Copyright © 2013 by the American Society of Nephrology.