FGF-23 and future cardiovascular events in patients with chronic kidney disease before initiation of dialysis treatment.
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.
Seiler
Sarah
S
Department of Internal Medicine IV, University of Saarland, Homburg, Germany. Sarahseiler@gmx.de
Reichart
Birgit
B
Roth
Daniel
D
Seibert
Eric
E
Fliser
Danilo
D
Heine
Gunnar H
GH
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000401:mortality; D002908:Chronic Disease; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005500:Follow-Up Studies; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000150:complications / Q000628:therapy*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011379:Prognosis; D006435:Renal Dialysis; D012307:Risk Factors; D015996:Survival Rate
D015415:Biomarkers; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23