Assessing Potential Heightened Sensitivity to Tenapanor in Japanese Patients on Hemodialysis (HD)

Background: Hyperphosphatemia is associated with arterial calcification, bone fractures, and cardiovascular mortality, making its treatment a cornerstone of dialysis care. However, strategies for managing hyperphosphatemia in patients undergoing maintenance dialysis, such as dietary restrictions and phosphate binders, yield only moderate efficacy. Tenapanor, the world's first phosphate absorption inhibitor, holds promise for addressing this challenge. Methods: We enrolled 88 patients with hyperphosphatemia despite the use of phosphate binders in our maintenance dialysis facility. Given that soft stools and diarrhea were the most frequently reported adverse events in previous trials, we initiated tenapanor administration at a minimal dose of 5mg once daily, gradually increasing it while monitoring gastrointestinal symptoms and phosphate reduction effects, and concurrently tapering phosphate binders. Results: The study population comprised 88 patients: 39 males, 19 females, with a mean age of 67 ± 12.1 years, mean dialysis vintage of 9.6 ± 6.5 years, and mean weight of 54.8 ±18.3 Kg. Within the first month of starting tenapanor, 27 patients discontinued treatment due to drug-related diarrhea, resulting in a dropout rate of 30.7%. Among the evaluable 61 patients, serum phosphate levels in those receiving 5mg of tenapanor once daily (n=10) decreased nonsignificantly from 6.08 ± 1.19 mg/dL to 5.27 ± 1.11 mg/dL, whereas in those escalated to 10mg once daily (n=51), there was a significant decrease from 5.47 ± 1.0 mg/dL to 4.73 ± 0.9 mg/dL, as depicted in the figure. Conclusion: The maintenance dosage of tenapanor has been established as 10-20mg orally twice daily in previous studies. While we observed a notably higher dropout rate due to diarrhea with tenapanor compared to previous reports, there remains potential for managing serum phosphate levels with relatively low doses of tenapanor in Japanese HD patients. The variability in tenapanor's effects, influenced not only by patient weight but also dietary habits and race, was suggested. Funding: Private Foundation Support