Pilot study of dietary phosphorus restriction and phosphorus binders to target fibroblast growth factor 23 in patients with chronic kidney disease.
BACKGROUND
High levels of fibroblast growth factor 23 (FGF23) are associated with mortality and progression of chronic kidney disease (CKD). Reducing dietary phosphorus intake lowers FGF23 secretion in healthly individuals, but there is little data on its effects in patients with pre-dialysis CKD.


METHODS
Using a 2×2 factorial design, we randomly assigned 16 normophosphataemic CKD stage 3-4 patients to receive a 2-week treatment with either lanthanum carbonate 1000 mg three times daily or placebo, and to ingest a tightly controlled diet containing 750 or 1500 mg of dietary phosphorus daily. We analysed serial measurements of FGF23, parathyroid hormone, serum phosphate and calcium, and 24-h urinary phosphate and calcium excretion using repeated-measures analyses.


RESULTS
Compared with the 1500-mg phosphorus diet, patients assigned to the 750-mg diet had greater reduction in 24-h urinary phosphate excretion (66% vs. 29%; P<0.0001). Lanthanum-treated patients experienced a significant reduction in 24-h urinary phosphate excretion compared with baseline (64%; P<0.0001), but the difference compared with placebo did not reach significance (64% vs. 31%). Despite the significant reductions in 24-h urinary phosphate excretion, no group demonstrated a significant reduction in FGF23 levels; FGF23 levels actually increased significantly in the 1500-mg diet plus placebo group, suggesting dietary phosphorus loading.


CONCLUSIONS
Although dietary phosphorus restriction and lanthanum lowered urinary phosphate excretion consistent with a rapid decrease in phosphorus absorption, inducing a reduction in FGF23 levels in CKD patients may require interventions with a longer duration than in healthy volunteers.
Isakova
Tamara
T
Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA. tisakova@med.miami.edu
Gutiérrez
Orlando M
OM
Smith
Kelsey
K
Epstein
Michael
M
Keating
Leigh K
LK
Jüppner
Harald
H
Wolf
Myles
M
D000368:Aged; D002614:Chelating Agents / Q000627:therapeutic use*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000178:diet therapy* / Q000188:drug therapy*; D007811:Lanthanum / Q000627:therapeutic use*; D008875:Middle Aged; D017553:Phosphorus Compounds / Q000378:metabolism*; D016226:Phosphorus, Dietary; D010865:Pilot Projects
D002614:Chelating Agents; C000717427:FGF23 protein, human; D017553:Phosphorus Compounds; D016226:Phosphorus, Dietary; C119467:lanthanum carbonate; D005346:Fibroblast Growth Factors; D007811:Lanthanum; D000089703:Fibroblast Growth Factor-23