Effect of Tenapanor on Serum Phosphate in Patients Receiving Hemodialysis

Abstract

Hyperphosphatemia is common among patients with CKD stage 5D and is associated with morbidity and mortality. Current guidelines recommend lowering serum phosphate concentrations toward normal. Tenapanor is a minimally absorbed small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 that functions in the gut to reduce sodium and phosphate absorption. This randomized, double-blind, placebo-controlled trial assessed the effects of tenapanor on serum phosphate concentration in patients with hyperphosphatemia receiving hemodialysis. After a 1- to 3-week washout of phosphate binders, we randomly assigned 162 eligible patients (serum phosphate =6.0 to <10.0 mg/dl and a 1.5-mg/dl increase from before washout) to one of six tenapanor regimens (3 or 30 mg once daily or 1, 3, 10, or 30 mg twice daily) or placebo for 4 weeks. The primary efficacy end point was change in serum phosphate concentration from baseline (randomization) to end of treatment. In total, 115 patients (71%) completed the study. Mean serum phosphate concentrations at baseline (after washout) were 7.32-7.92 mg/dl for tenapanor groups and 7.87 mg/dl for the placebo group. Tenapanor provided dose-dependent reductions in serum phosphate level from baseline (least squares mean change: tenapanor =0.47-1.98 mg/dl; placebo =0.54 mg/dl; P=0.01). Diarrhea was the most common adverse event (tenapanor =18%-68%; placebo =12%) and frequent at the highest tenapanor doses. In conclusion, tenapanor treatment resulted in statistically significant, dose-dependent reductions in serum phosphate concentrations in patients with hyperphosphatemia receiving hemodialysis. Additional studies are required to clarify the optimal dosing of tenapanor in patients with CKD-related hyperphosphatemia.

Keywords: NHE3; chronic kidney disease; hemodialysis; hyperphosphatemia; sodium–hydrogen exchanger 3; tenapanor.

Figure 1.

Patient flow diagram. b.i.d., Twice daily; q.d., once daily. ^aSerum phosphate was monitored weekly during washout, and patients were randomized after 1–3 weeks after eligibility criteria were met; ^bpatients who attended the end of treatment period visit irrespective of treatment duration; ^cafter the end of treatment or early termination, patients resumed their prestudy phosphate binder medication and returned for a follow-up visit after 1–2 weeks.

Figure 2.

Tenapanor treatment resulted in dose-dependent reductions in serum phosphate from baseline to the end of treatment. Graph shows least squares mean changes at end of treatment (EOT)/early termination (ET; i.e., the last available measurement during the treatment period). Error bars show lower limits of 95% CIs. b.i.d., Twice daily; q.d., once daily. *P<0.05 versus placebo (analysis of covariance; t test); ^amean±SD; ^bleast squares mean (95% CI): P=0.01 (analysis of covariance; F test).