Effect of niacin on FGF23 concentration in chronic kidney disease

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.

Conflict of interest statement

Conflicts of Interest:

NCT00269204 was sponsored by Merck, Sharp & Dohme Corporation. Funding for the assays for FGF23, PTH and 25-OHD was provided in a separate grant by Merck, Sharp & Dohme Corporation. Dr Ix has received honoraria from Keryx Biopharmaceuticals and Shire Pharmaceuticals.

Figures

Figure 1

A–C: Box plots showing serum Phosphorus (Figure 1A), FGF23 (Figure 1B) and PTH (Figure 1C) concentrations at baseline and at 24 weeks in each of the three group assignments. A significant decline in serum FGF23 concentrations is seen in the ERN group, but not in the ERN-L or placebo groups.