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 >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 >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.

Phosphate Toxicity in CKD: The Killer among Us

“…Nicotinamide (niacinamide and vitamin B3) reduces dietary phosphate absorption and decreases serum phosphate levels in patients by inhibiting expression of NaPi-2b (124,125). Nicotinamide also has a phosphaturic effect independent of PTH, which may be the result of nicotinamide reducing levels of renal NaPi-2a and NaPi-2c in the kidney (126).…”

Npt2b Deletion Attenuates Hyperphosphatemia Associated with CKD

“…Phosphate lowering effects have been shown in preclinical models and in humans treated with either nicotinamide or its precursor, niacin. [7][8][9][10] Nicotinamide has been shown to inhibit sodium-dependent phosphate transport activity in rat small intestine, reduce Npt2b mRNA expression, and attenuate hyperphosphatemia in an adenine-induced renal failure model. 11,12 Reduction in serum phosphate with corresponding modulation of Npt2a and 2b mRNA expression has also been observed in rats treated with liver X receptor agonists.…”

Stop chronic kidney disease progression: Time is approaching

“…A single study looked for non-inferiority of Sucroferric oxyhydroxide (PA21) compared to sevelamer carbonate concerning phosphate binding [141] . The value of nicotinamide in phosphate control (as well as its effects on lipid levels) was explored in some short-term trials on dialysis patients [142][143][144] . However, such trials did not look for either pharmacokinetics or safety.…”