TY - JOUR
T1 - Pilot study of dietary phosphorus restriction and phosphorus binders to target fibroblast growth factor 23 in patients with chronic kidney disease
AU - Isakova, Tamara
AU - Gutirrez, Orlando M.
AU - Smith, Kelsey
AU - Epstein, Michael
AU - Keating, Leigh K.
AU - Jppner, Harald
AU - Wolf, Myles
N1 - Funding Information:
Acknowledgements. This study was supported by a grant from Shire Pharmaceuticals, a grant from the American Kidney Fund Clinical Scientist in Nephrology Fellowship (T.I.), grants from the National Institutes of Health: K23DK081673 (O.M.G.), RO1DK076116 (M.W.) and R01DK081374 (M.W.), and grants UL1RR025758-01 and M01RR01066 from the National Institutes of Health National Center for Research Resources. Shire Pharmaceuticals gave full rights of publication to the investigators. Shire did review the manuscript but did not participate in the conceptual design, data analysis, interpretation of the results or writing of the manuscript. Parts of this manuscript were presented in abstract form at the National Kidney Foundation Spring Clinical Meeting in Orlando, FL, USA, 14–17 April 2010.
PY - 2011/2
Y1 - 2011/2
N2 - 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 34 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.
AB - 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 34 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.
KW - FGF23
KW - chronic kidney disease
KW - phosphate
KW - phosphate binders
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U2 - 10.1093/ndt/gfq419
DO - 10.1093/ndt/gfq419
M3 - Article
C2 - 20631407
AN - SCOPUS:79551500014
SN - 0931-0509
VL - 26
SP - 584
EP - 591
JO - Proceedings of the European Dialysis and Transplant Association - European Renal Association. European Dialysis and Transplant Association - European Renal Association. Congress
JF - Proceedings of the European Dialysis and Transplant Association - European Renal Association. European Dialysis and Transplant Association - European Renal Association. Congress
IS - 2
ER -