Journal Article

FGF-23 and future cardiovascular events in patients with chronic kidney disease before initiation of dialysis treatment

Sarah Seiler, Birgit Reichart, Daniel Roth, Eric Seibert, Danilo Fliser and Gunnar H. Heine

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 25, issue 12, pages 3983-3989
Published in print December 2010 | ISSN: 0931-0509
Published online June 2010 | e-ISSN: 1460-2385 | DOI:
FGF-23 and future cardiovascular events in patients with chronic kidney disease before initiation of dialysis treatment

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Background. High levels of the phosphaturic hormone fibroblast growth factor 23 (FGF-23) predict mortality in haemodialysis patients. The prognostic relevance of increased plasma FGF-23 levels in patients with less advanced chronic kidney disease (CKD) who are not on dialysis therapy is presently unknown.

Methods. We measured plasma c-terminal FGF-23 levels in 149 CKD patients not undergoing dialysis treatment. Patients were stratified by their baseline FGF-23 levels (>104 vs ≤104 rU/mL) and followed for a period of 4.8 ± 0.9 years. During the follow-up, the pre-specified combined clinical endpoint was the first occurrence of a cardiovascular event, e.g. myocardial infarction, coronary artery angioplasty/stenting/bypass surgery, stroke, carotid endarterectomy/stenting, non-traumatic lower extremity amputation, lower limb artery surgery/angioplasty/stenting or death.

Results. At baseline, elevated FGF-23 levels >104 rU/mL were associated with more advanced CKD. Traditional cardiovascular risk factors and prevalent cardiovascular disease did not differ between CKD patients with high vs low FGF-23 levels. Fifty patients experienced a cardiovascular event during follow-up. Compared with CKD patients with FGF-23 ≤104 rU/mL, CKD patients with FGF-23 levels above the cut-off had worse event-free survival at univariate (log-rank test P = 0.012) and multivariate analysis [hazard ratio 2.49 (95% CI 1.40–4.39); P = 0.002].

Conclusions. Elevated FGF-23 plasma levels predict cardiovascular events in CKD patients not on dialysis therapy. This finding complements two recent cohort studies in which incident and prevalent haemodialysis patients with highest FGF-23 levels had worst survival. Lowering FGF-23 levels (e.g. by oral phosphate binder medication) could emerge as a promising new therapeutic option to reduce cardiovascular morbidity in CKD patients.

Keywords: cardiovascular mortality; CKD; FGF-23; klotho; phosphate

Journal Article.  3829 words.  Illustrated.

Subjects: Nephrology

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