Fibroblast growth factor-23 and cardiovascular events in CKD

Julia J. Scialla, Huiliang Xie, Mahboob Rahman, Amanda Hyre Anderson, Tamara Isakova, Akinlolu Ojo, Xiaoming Zhang, Lisa Nessel, Takayuki Hamano, Juan E. Grunwald, Dominic S. Raj, Wei Yang, Jiang He, James P. Lash, Alan S. Go, John W. Kusek, Harold Feldman, Myles Wolf

Research output: Contribution to journalArticlepeer-review

241 Scopus citations

Abstract

An elevated level of fibroblast growth factor-23 (FGF-23) is the earliest abnormality of mineral metabolism in CKD. High FGF-23 levels promote left ventricular hypertrophy but not coronary artery calcification. We used survival analysis to determine whether elevated FGF-23 is associated with greater risk of adjudicated congestive heart failure (CHF) and atherosclerotic events (myocardial infarction, stroke, and peripheral vascular disease) in a prospective cohort of 3860 participants with CKD stages 2-4 (baseline estimated GFR [eGFR], 44±15 ml/minper 1.73m2).Duringamedian follow-upof3.7 years, 360 participants werehospitalized for CHF (27 events/1000 person-years) and 287 had an atherosclerotic event (22 events/1000 person-years). After adjustment for demographic characteristics, kidney function, traditional cardiovascular risk factors, and medications, higher FGF-23 was independently associated with graded risk of CHF(hazard ratio [HR], 1.45 per doubling [95% confidence interval (CI), 1.28 to 1.65]; HR for highest versus lowest quartile, 2.98 [95% CI, 1.97 to 4.52]) and atherosclerotic events (HR per doubling, 1.24 [95% CI, 1.09 to1.40]; HRfor highest versus lowest quartile, 1.76 [95% CI, 1.20 to 2.59]). Elevated FGF-23 was associated more strongly with CHF than with atherosclerotic events (P=0.02), and uniformly was associated with greater risk of CHF events across subgroups stratified by e GFR, proteinuria, prior heart disease, diabetes, BP control, anemia, sodium intake, income, fat-free mass, left ventricular mass index, and ejection fraction. Thus, higher FGF-23 is independently associated with greater risk of cardiovascular events, particularly CHF, in patients with CKD stages 2-4.

Original languageEnglish (US)
Pages (from-to)349-360
Number of pages12
JournalJournal of the American Society of Nephrology
Volume25
Issue number2
DOIs
StatePublished - Feb 2014

ASJC Scopus subject areas

  • Nephrology

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