A randomized, double-blind, placebo-controlled trial of niacinamide for reduction of phosphorus in hemodialysis patients

Abstract

Background and objectives: Niacinamide inhibits intestinal sodium/phosphorus transporters and reduces serum phosphorus in open-label studies. A prospective, randomized, double-blind, placebo-controlled crossover trial was performed for assessment of the safety and efficacy of niacinamide.

Design, setting, participants, & measurements: Hemodialysis patients with phosphorus levels > or =5.0 mg/dl were randomly assigned to 8 wk of niacinamide or placebo, titrated from 500 to 1500 mg/d. After a 2-wk washout period, patients switched to 8 wk of the alternative therapy. Vitamin D analogs and calcimimetics were held constant; phosphorus binders were not changed unless safety criteria were met.

Results: Thirty-three patients successfully completed the trial. Serum phosphorus fell significantly from 6.26 to 5.47 mg/dl with niacinamide but not with placebo (5.85 to 5.98 mg/dl). A concurrent fall in calcium-phosphorus product was seen with niacinamide, whereas serum calcium, intact parathyroid hormone, uric acid, platelet, triglyceride, LDL, and total cholesterol levels remained stable in both arms. Serum HDL levels rose with niacinamide (50 to 61 mg/dl but not with placebo. Adverse effects were similar between both groups. Among patients who were > or =80% compliant, results were similar, although the decrease in serum phosphorus with niacinamide was more pronounced (6.45 to 5.28 mg/dl) and the increase in HDL approached significance (49 to 58 mg/dl).

Conclusions: In hemodialysis patients, niacinamide effectively reduces serum phosphorus when co-administered with binders and results in a potentially advantageous increase in HDL cholesterol. Further study in larger randomized trials and other chronic kidney disease populations is indicated.

Figures

Figure 1.

After a 2-wk screening phase, patients were randomly assigned to 8 wk of niacinamide or placebo with titration from 250 to 750 mg twice daily. A 2-wk washout preceded the switch from niacinamide to placebo or vice versa.

Figure 2.

After the 2-wk screening period, 33 patients were enrolled in the study. All patients completed the study; 25 demonstrated compliance with the study regimen and were included in the per-protocol analysis.

Figure 3.

Serum phosphorus levels rose during the 8 wk of the placebo arm (solid line) but decreased significantly during treatment with niacinamide (dotted line). Placebo n = 33; niacinamide n = 33.

Figure 4.

Effect of niacinamide on HDL cholesterol levels is shown in both randomization schemes. Among all patients, HDL cholesterol levels increased significantly on niacinamide (50 to 61 mg/dl; P = 0.035). Placebo n = 33; niacinamide n = 33.

Figure 5.

Serum phosphorus is represented by the solid line during the placebo arm and the dotted line during niacinamide. Among compliant patients, a more pronounced difference was noted in the change in serum phosphorus between placebo and niacinamide (+0.37 on placebo versus −1.17 mg/dl on niacinamide; P = 0.002). Placebo n = 25; niacinamide n = 25.