Phosphate Management in Hemodialysis Patients

Despite the widespread use of phosphate binders (PBs), many hemodialysis patients have poor phosphate control.

Preliminary clinical data show that nicotinamide, when used with phosphate binders (PBs), may enhance phosphate management. Nicotinamide modified release (NAMR) paired with oral PB considerably improves phosphate management in hemodialysis patients, according to a new research.

This study was conducted by Markus Ketteler and team, the findings of which are published in Kidney International Reports.

This was a multinational, randomized, double-blind, placebo-controlled study that looked at the efficacy and safety of NAMR in combination with oral PB in a large group of hemodialysis patients who had abnormal serum phosphate concentrations (>4.5 mg/dl) despite receiving PB treatment. Patients were placed in a proof-of-efficacy phase (12 weeks [W12]) during which no changes to relevant medication were permitted, followed by a safety extension period lasting up to 52 weeks. The first phase's findings are shown here.

Main Findings of the Study

• In the intention-to-treat (ITT) population, there were 539 NAMR patients and 183 placebo patients.
• NAMR and a placebo were taken orally once a day (250–1500 mg/d). The average age of the patients was 61.8 years, and 63.0% of them were men.
• NAMR outperformed placebo in the confirmatory analysis that calculated the change in serum phosphate concentration after 12 weeks, with a significant difference of –0.51 mg/dl (95% confidence interval [CI] –0.72, –0.29; P 0.0001).
• This result was related with considerably reduced intact parathyroid hormone (iPTH) levels (NAMR: 292.4±300.4 pg/ml vs. placebo: 337.0±302.7 pg/ml; P = 0.04) and an improved calcification propensity (T50 time; NAMR: 23.8±97.1 minutes vs. placebo: 2.3±100.7 minutes; P = 0.02).
• In the NAMR group, diarrhea and pruritus were more common.

In conclusion, the findings of this phase III study demonstrate the phosphate-lowering potential of nicotinamide modified release as an add-on treatment strategy to proven, but inadequately effective, phosphate binder therapy in hemodialysis patients. Researchers further suggest that the extra phosphate decrease may be related with improvements in other CKD-MBD characteristics.

Reference

Ketteler M, Wiecek A, Rosenkranz AR, et al. Efficacy and safety of a novel nicotinamide modified-release formulation in the treatment of refractory hyperphosphatemia in patients receiving hemodialysis—a randomized clinical trial. Kidney Int Rep. 6(3):594-604. doi:10.1016/j.ekir.2020.12.012