Comparative Phosphate-Lowering Effects of Tenapanor in Combination with Different Phosphate Binders in Patients on Hemodialysis: A Prospective Pilot Study

Background: Hyperphosphatemia is a well-known contributor to cardiovascular morbidity and mortality in patients receiving hemodialysis (HD). Despite the widespread use of phosphate binders, approximately 30% of Japanese HD patients fail to achieve target serum phosphate (P) levels. Tenapanor, a novel phosphate absorption inhibitor, represents a new therapeutic strategy. However, its modest efficacy as monotherapy necessitates combination with conventional phosphate binders. The optimal combination strategy remains unclear. Methods: In this prospective study, 55 HD patients were stratified into five groups based on their baseline phosphate binder (PB) use: PB-naïve, calcium-based binders, iron-based binders (ferric citrate), lanthanum carbonate, and polymer-based binders. All patients received additional tenapanor (10 mg twice daily) for one week. Serum phosphate reduction rates were compared across groups. In a secondary analysis, patients were also regrouped based on absence of each PB class (e.g., non-iron, non-Ca, etc.). Results: The phosphate reduction rate was highest in the PB-naïve group (26.7%), followed by lanthanum (19.8%), calcium-based (19.7%), polymer-based (17.3%), and iron-based (9.1%) groups. In patients not receiving each PB class, only the non-iron group showed a significantly greater phosphate reduction (20.2%) compared to the iron group (9.1%, p < 0.05). No significant differences were observed for the other binder classes. Conclusion: Our findings suggest that concomitant use of iron-based phosphate binders may attenuate the phosphate-lowering effect of tenapanor in HD patients. Although the exact mechanism remains unclear, it is hypothesized that iron-based binders such as ferric citrate may alter intestinal pH—potentially affecting the local action of tenapanor. These preliminary results highlight the importance of binder selection in maximizing tenapanor efficacy and warrant further mechanistic and clinical studies. Funding: Private Foundation Support