Nicotinamide suppresses hyperphosphatemia in hemodialysis patients

Abstract

The use of calcium- or aluminum-based phosphate binders against hyperphosphatemia is limited by the adverse effects of hypercalcemia or aluminum toxicity in long-term hemodialysis. Because nicotinamide is an inhibitor of sodium-dependent phosphate cotransport in rat renal tubule and small intestine, we examined whether nicotinamide reduces serum levels of phosphorus and intact parathyroid hormone (iPTH) in patients undergoing hemodialysis. Sixty-five hemodialysis patients with a serum phosphorus level of more than 6.0 mg/dL after a 2-week washout of calcium carbonate were enrolled in this study. Nicotinamide was administered for 12 weeks. The starting dose was 500 mg/day, and the dose was increased by 250 mg/day every 2 weeks until serum phosphorus levels were well controlled at less than 6.0 mg/dL. A 2-week posttreatment washout period followed the cessation of nicotinamide. Blood samples were collected every week for measurement of serum calcium, phosphorus, lipids, iPTH, and blood nicotinamide adenine dinucleotide (NAD). The mean dose of nicotinamide was 1080 mg/day. The mean blood NAD concentration increased from 9.3 +/- 1.9 nmol/105 erythrocytes before treatment to 13.2 +/- 5.3 nmol/105 erythrocytes after treatment (P < 0.01). The serum phosphorus concentration increased from 5.4 +/- 1.5 mg/dL to 6.9 +/- 1.5 mg/dL with the pretreatment washout, then decreased to 5.4 +/- 1.3 mg/dL after the 12-week nicotinamide treatment (P < 0.0001), and rose again to 6.7 +/- 1.6 mg/dL after the posttreatment washout. Serum calcium levels decreased during the pretreatment washout from 9.1 +/- 0.8 mg/dL to 8.7 +/- 0.7 mg/dL with the cessation of calcium carbonate. No significant changes in serum calcium levels were observed during nicotinamide treatment. Median serum iPTH levels increased with pretreatment washout from 130.0 (32.8 to 394.0) pg/mL to 200.0 (92.5 to 535.0) pg/mL and then decreased from the maximum 230.0 (90.8 to 582.0) pg/mL to 150.0 (57.6 to 518.0) pg/mL after the 12-week nicotinamide treatment (P < 0.05). With nicotinamide, serum high-density lipoprotein (HDL) cholesterol concentrations increased from 47.4 +/- 14.9 mg/dL to 67.2 +/- 22.3 mg/dL (P < 0.0001) and serum low-density lipoprotein (LDL) cholesterol concentrations decreased from 78.9 +/- 18.8 mg/dL to 70.1 +/- 25.3 mg/dL (P < 0.01); serum triglyceride levels did not change significantly. Nicotinamide may provide an alternative for controlling hyperphosphatemia and hyperparathyroidism without inducing hypercalcemia in hemodialysis patients.