Effect of niacin on FGF23 concentration in chronic kidney disease

Am J Nephrol. 2014;39(6):484-90. doi: 10.1159/000362424. Epub 2014 May 20.

Abstract

Background: Elevated serum phosphorus and FGF23 are independent cardiovascular risk factors in patients with chronic kidney disease. In a randomized controlled trial of patients with dyslipidemia assigned to either extended release niacin (ERN) alone, ERN combined with the selective prostaglandin D2 receptor subtype 1 inhibitor laropiprant (ERN-L) or placebo, niacin lowered serum phosphorus; however, it is not known if it lowers FGF23 concentrations.

Methods: This is an ancillary study to a multicenter, randomized, double-blind, placebo-controlled trial among patients with dyslipidemia and an estimated glomerular filtration rate (eGFR) of 30-74 ml/min/1.73 m(2). Participants were randomized to ERN-L (n = 162), ERN (n = 97), or placebo (n = 68) in a 3:2:1 ratio for 24 weeks. The primary outcome was a change in serum FGF23 concentrations, and secondary outcomes were changes in other mineral metabolism parameters.

Results: Both the ERN and ERN-L groups showed significant declines in serum phosphorus, calcium and calcium·phosphorus product at 24 weeks compared to placebo. A significant decline from baseline (10.9%, p < 0.01) in the serum FGF23 concentration was observed in the ERN group compared to placebo, but not in the ERN-L group compared to placebo (p = 0.36 and 0.97 for ERN-L and placebo, respectively), despite equivalent declines in serum phosphorus. Similarly, the most marked declines in PTH occurred in the ERN-only group versus placebo; no change in PTH was observed in the ERN-L group.

Conclusions: In this ancillary study of hyperlipidemic patients with an eGFR of 30-74 ml/min/1.73 m(2), ERN alone but not in combination with laropiprant lowered FGF23 and PTH concentrations. If confirmed, niacin may provide a novel strategy to decrease phosphorus, FGF23, and PTH concentrations in patients with chronic kidney disease.

Trial registration: ClinicalTrials.gov NCT00269204.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Calcium / blood
  • Delayed-Action Preparations
  • Double-Blind Method
  • Drug Therapy, Combination
  • Dyslipidemias / complications
  • Dyslipidemias / drug therapy*
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / drug effects
  • Fibroblast Growth Factors / metabolism*
  • Humans
  • Hypolipidemic Agents / therapeutic use*
  • Indoles / pharmacology
  • Indoles / therapeutic use*
  • Male
  • Middle Aged
  • Niacin / pharmacology
  • Niacin / therapeutic use*
  • Parathyroid Hormone / blood
  • Phosphorus / blood
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Prostaglandin / antagonists & inhibitors*
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / metabolism*

Substances

  • Delayed-Action Preparations
  • FGF23 protein, human
  • Hypolipidemic Agents
  • Indoles
  • MK-0524
  • Parathyroid Hormone
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • Niacin
  • Phosphorus
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • Calcium
  • prostaglandin D2 receptor

Associated data

  • ClinicalTrials.gov/NCT00269204