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.

• Authors: Madhumathi Rao, Michael Steffes, Andrew Bostom, Joachim H Ix
• Journal: American journal of nephrology (Am J Nephrol) Vol. 39 Issue 6 Pg. 484-90 ( 2014) ISSN: 1421-9670 [Electronic] Switzerland
• PMID: 24854458 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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