Abstract
BackgroundHigh levels of circulating fibroblast growth factor 23 (FGF23) are associated with chronic kidney disease (CKD) progression and high mortality. In the Phosphate Reduction Evaluation of FGF23 in Early CKD Treatment (PREFECT) study, we assessed the effect of reducing intestinal phosphate absorption using lanthanum carbonate on FGF23 levels in normophosphatemic patients with CKD stage 3.MethodsThirty-five individuals were randomized to lanthanum carbonate 3000 mg/day (n = 23) or placebo (n = 12) for 12 weeks. Levels of intact FGF23 (iFGF23), C-terminal FGF23, serum and urinary phosphate and calcium, intact parathyroid hormone and 1,25-dihydroxyvitamin D were assessed.ResultsThe median age was 65 years in the lanthanum group and 73 years in the placebo group; 58.8% and 41.7% were men, respectively. No significant difference was seen in mean iFGF23 between groups at week 12. There was, however, a transient reduction from baseline in iFGF23 in the lanthanum group at week 1, from 70.5 pg/ml to 51.9 pg/ml, which was not seen in the placebo group; this between-group difference in percentage change from baseline was significant in post hoc analyses (p = 0.0102). Urinary phosphate decreased after 1 week of lanthanum treatment and remained low at week 12.ConclusionsReducing intestinal phosphate absorption with lanthanum carbonate did not lead to sustained reductions in iFGF23 in patients with CKD stage 3, although phosphaturia decreased. This suggests that factors other than phosphate burden may be responsible for driving increases in circulating FGF23 in patients with CKD.Trial registrationClinicalTrials.gov NCT01128179, 20 May 2010.
Highlights
High levels of circulating fibroblast growth factor 23 (FGF23) are associated with chronic kidney disease (CKD) progression and high mortality
The increase in FGF23 levels with progressing CKD probably occurs as part of the skeletal response to increased phosphate burden that results from a reduced number of functional nephrons [15]
This hypothesis was supported by a previous study of 18 patients with CKD stage 3, which showed that FGF23 levels were significantly reduced after 4 weeks of treatment with lanthanum carbonate 2250 mg/ day, and that urinary phosphate excretion was reduced [19]
Summary
High levels of circulating fibroblast growth factor 23 (FGF23) are associated with chronic kidney disease (CKD) progression and high mortality. FGF23 can directly induce left ventricular hypertrophy, which can be prevented by blocking the intracellular signaling pathway stimulated by FGF23 [13]. It is not clear, whether increased circulating FGF23 levels in patients with CKD are causative of cardiovascular disease, or whether FGF23 is a biomarker for CKD-MBD severity [14]. The increase in FGF23 levels with progressing CKD probably occurs as part of the skeletal response to increased phosphate burden that results from a reduced number of functional nephrons [15]. Modest increases (33%) in dietary phosphate were not associated with increased FGF23 levels [17]
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