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.