Effects of dietary phosphate restriction and phosphate binders on FGF23 levels in CKD

Abstract

Background: Elevated levels of fibroblast growth factor 23 (FGF23) are associated with increased risk of adverse outcomes in patients with CKD. Reducing dietary phosphate intake or absorption may decrease FGF23 levels, but data on the combined effects of dietary phosphate restriction and phosphate binders in CKD are limited.

Design, setting, participants, & measurements: In this 2×2 factorial, single-blinded, placebo-controlled, 3-month study, conducted between July 2009 and March 2012, 39 patients with CKD stages 3 or 4 and normal serum phosphate levels were randomly assigned to one of four groups: ad libitum diet plus lanthanum carbonate (LC) placebo (n=10), 900-mg phosphate diet plus LC placebo (n=10), ad libitum diet plus LC (n=11), or 900-mg phosphate diet plus LC (n=8). The dose of LC was 1000 mg three times daily with meals. Dietary restriction was accomplished with outpatient counseling. The primary end point was change in FGF23 levels from baseline.

Results: Compared with ad libitum diet, the 900-mg phosphate diet did not significantly reduce FGF23 levels (diet × time interaction, P=0.05). Compared with placebo, LC alone also did not significantly reduce FGF23 levels (LC × time interaction, P=0.21). However, the dual intervention significantly decreased FGF23 levels throughout the study period (diet × LC × time interaction, P=0.02), resulting in a 35% (95% confidence interval, 8%-62%) reduction by study end.

Conclusion: The combination of LC plus counseling for a phosphate-restricted diet decreased FGF23 levels in patients with CKD stages 3-4 and normal serum phosphate levels.

Trial registration: ClinicalTrials.gov NCT00843349.

Figures

Figure 1.

Study design and flow of participants. (A) Study design. (B) Thirty-nine patients completed 3 months of interventions according to random assignment to one of four groups: ad libitum diet plus lanthanum carbonate (LC) placebo, 900-mg phosphate (P) diet plus LC placebo, ad libitum diet plus LC and 900-mg P diet plus LC.

Figure 2.

Average daily doses of lanthanum carbonate (LC) during the study. Mean ± SD dose of lanthanum carbonate throughout the study is shown for each treated group in relation to the protocol specified dose, indicated by the dashed horizontal gray line.

Figure 3.

Combined effects of lanthanum carbonate (LC) and dietary intervention on fibroblast growth factor 23 (FGF23) and other markers of mineral metabolism according to four treatment groups. (A–D) Mean values for 24-hour urinary phosphate, serum phosphate, FGF23, and parathyroid hormone (PTH) throughout the study period. (E–H) Percentage changes in these measures from baseline.

Figure 4.

Effects of lanthanum carbonate (LC) and dietary intervention on fibroblast growth factor 23 (FGF23) in individual participants according to four treatment groups. Percentage changes in FGF23 from baseline to end of study for individual patients.