Introduction Tenapanor is a minimally absorbed, small-molecule inhibitor of sodium/hydrogen exchanger 3 and thus suppresses sodium absorption in the gastrointestinal tract. It is approved by the FDA for the treatment of hyperphosphatemia in dialysis patients. This randomized controlled trial evaluated its efficacy in the treatment of hyperphosphatemia and constipation in hemodialysis patients.

Methods Ninety hemodialysis patients were randomized 1:1 to receive either tenapanor or standard care. Randomization was performed using a computer-generated sequence stratified by baseline serum phosphorus levels. The tenapanor group began treatment with a dosage of 10 mg/day, which was adjusted based on serum phosphorus levels. Primary outcomes were changes in serum phosphorus levels in the tenapanor and control groups and changes in stool consistency, assessed weekly using the Bristol Stool Form Scale (BSFS) in the tenapanor group. Secondary outcomes included laxative use and phosphate binder prescription patterns. Serum phosphorus levels, serum calcium, albumin, and related biochemical parameters were monitored every two weeks. Data were analyzed using intention-to-treat principles. This study was not blinded.

Results Of the 90 randomized participants, 69 completed the 23-week study. Tenapanor significantly improved stool consistency and resolved constipation (BSFS types 1-2) by week 5. A transient increase in loose stools (BSFS types 6-7) occurred early, with 10 participants discontinuing due to diarrhea. Laxative use decreased significantly in the tenapanor group, from 58.2% at baseline to 35.6% at week 23 (p < 0.01). Serum phosphorus levels were decreased in both groups, with comparable control. Lanthanum carbonate prescriptions decreased significantly in the tenapanor group and were largely replaced by low-dose tenapanor.

Conclusion Tenapanor improves stool consistency, reduces laxative use, and provides effective phosphorus control in hemodialysis patients and represents a promising alternative to conventional phosphate binders.

The authors have declared no competing interest.

the University Hospital Medical Information Network Clinical Trials Registry under trial number UMIN000033778 (UMIN-CTR URL: http://www.umin.ac.jp/ctr/index.htm) We acknowledge that there is a discrepancy between the date of trial registration and the date of participant recruitment. Recruitment for this study was conducted from February 1, 2024, to February 28, 2024, while the trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) on December 25, 2024. This oversight occurred due to an unintentional administrative delay in completing the trial registration process. We recognize the importance of prospective trial registration in ensuring transparency, minimizing potential biases, and aligning with ethical and regulatory guidelines. To address this, we took the following steps: Full Disclosure: We are reporting this discrepancy in the manuscript to maintain transparency. Protocol Consistency: The trial was conducted strictly in accordance with the original protocol, which was developed and finalized before the start of participant recruitment. No changes were made to the study design, eligibility criteria, data collection procedures, or statistical analysis plans after the study was initiated. Ethical Oversight: The study received ethical approval from the Ethics Committee for Human Research at Tojinkai Hospital (Approval Number: 2024-03) prior to the commencement of recruitment. Written informed consent was obtained from all participants before enrollment. We sincerely regret this oversight and have implemented measures to ensure that all future studies are prospectively registered before recruitment begins. We believe that this explanation, combined with the steps taken to ensure the integrity of the study, demonstrates our commitment to upholding ethical standards and transparency in research.

The author(s) received no specific funding for this work.

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Ethical approval was granted by the Ethics Committee for Human Research at Tojinkai Hospital (Approval Number: 2024-03).

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