Clinical Changes After Tenapanor Initiation in Maintenance Hemodialysis Patients: A Two-Center Retrospective Observational Study

Background Hyperphosphatemia is common in patients on hemodialysis. It is often difficult to control because of high pill burden and adverse effects of phosphate binders. Tenapanor, an inhibitor of intestinal Na+/H+ exchanger isoform 3 (NHE3), reduces paracellular phosphate transport. Here we assessed tenapanor's effectiveness in routine hemodialysis practice. Methods Our retrospective observational study was done at two outpatient centers in Japan. Forty-one adults on maintenance hemodialysis started tenapanor (5 mg twice daily). Patients who discontinued the drug due to diarrhea were not included in the study. For each patient, the baseline evaluation means for 12 weeks were compared with the 12-week evaluation means after a stabilization period. Outcomes were serum phosphate and other biochemistry parameters, phosphate binder tablet count and phosphate binding capacity (PBC), interdialytic weight gain (IDWG), and blood pressure. Paired differences and associations among metrics changes (Δ) were tested. Results Serum phosphate decreased from 6.5±1.2 to 5.4±1.3 mg/dL (p<0.001). Binder tablet intake and PBC decreased significantly. IDWG declined from 3.1±1.1 to 2.9±1.0 kg (p=0.016). Systolic and diastolic blood pressure also decreased significantly. Of note, Δ IDWG correlated with Δ phosphate (r=0.35, p=0.024). Conclusions In patients on hemodialysis, the addition of tenapanor was associated with the improvement of phosphate control and reduced binder burden and PBC. It was also linked with a reduction of IDWG modestly, but significantly, without adverse changes in key laboratory parameters. The correlation between the reduction of IDWG and that of serum phosphate might reflect a direct link between sodium/water and phosphate absorption.