{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:53:36Z","timestamp":1790920416642,"version":"4.1.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":92,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004095","name":"Kyowa Kirin","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004095","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Using phosphate binders (PBs) to control hyperphosphatemia in patients undergoing hemodialysis is associated with substantial pill burden. In this post hoc phase 3 analysis, we evaluated the benefit of the selective sodium\/hydrogen exchanger isoform 3 inhibitor, tenapanor, in reducing pill burden in these patients. Patients received oral tenapanor starting at 5\u00a0mg twice daily and PBs. Dose adjustments of PBs and tenapanor were based on serum phosphorus levels. Changes in daily PB pill count, daily equivalent dose of PBs, number of combined PBs used, PB dose frequency, and tenapanor dose at Week 50 were analyzed according to patient background factors. The analysis comprised 204 patients (followed up for Week 50: 154 patients). Factors affecting the tenapanor dose at Week 50 were sex (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.029), age (&lt;\u200965 vs.\u2009\u2265\u200965\u00a0years;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.008), normalized protein catabolic rate (&lt;\u20090.80 vs.\u2009\u2265\u20091.00;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.019), presence of diabetic nephropathy (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.038), constipation (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.015), and the occurrence of diarrhea as an adverse event (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.009). Tenapanor consistently reduced the daily PB pill count and equivalent dose of PBs from baseline to Week 50 across all patient background factors evaluated (all\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001 vs. baseline), thus demonstrating the clinical benefit of tenapanor regardless of patient background characteristics.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Clinical Trial Registration<\/jats:italic>\n                    ClinicalTrials.Gov (NCT04771780)\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-58594-9","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T17:35:39Z","timestamp":1782927339000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tenapanor reduces phosphate binder pill burden among hemodialysis patients in a post hoc phase 3 analysis"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6527-3286","authenticated-orcid":false,"given":"Nobuo","family":"Nagano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Tokunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Asada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Fukagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadao","family":"Akizawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"58594_CR1","doi-asserted-by":"publisher","first-page":"553","DOI":"10.4009\/jsdt.54.553","volume":"54","author":"N Nagano","year":"2021","unstructured":"Nagano, N. et al. Acceptable number of oral pills that can be taken at one time by dialysis patients. J. Jpn. Soc. Dial. Ther. 54, 553\u2013559 (2021) ([In Japanese]).","journal-title":"J. Jpn. Soc. Dial. Ther."},{"key":"58594_CR2","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s41100-021-00322-2","volume":"7","author":"N Nagano","year":"2021","unstructured":"Nagano, N. et al. Prescription characteristics of phosphate binders in a high pill burden for hemodialysis patients. Ren. Replace. Ther. 7, 5 (2021).","journal-title":"Ren. Replace. Ther."},{"key":"58594_CR3","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1111\/1744-9987.13813","volume":"26","author":"N Nagano","year":"2022","unstructured":"Nagano, N. et al. Impact of phosphate binders on medication dosing frequency, timing, and number of prescribed pills in hemodialysis patients. Ther. Apher. Dial. 26, 1174\u20131181 (2022).","journal-title":"Ther. Apher. Dial."},{"key":"58594_CR4","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.2215\/CJN.00290109","volume":"4","author":"Y Chiu","year":"2009","unstructured":"Chiu, Y. et al. Pill burden, adherence, hyperphosphatemia, and quality of life in maintenance dialysis patients. Clin. J. Am. Soc. Nephrol. 4, 1089\u20131096 (2009).","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"58594_CR5","doi-asserted-by":"publisher","first-page":"475","DOI":"10.4009\/jsdt.49.475","volume":"49","author":"K Ito","year":"2016","unstructured":"Ito, K. et al. The prescription of a higher number of phosphate binder pills is associated with lower medication adherence and worse serum phosphorus control. J. Jpn. Soc. Dial. Ther. 49, 475\u2013482 (2016) ([In Japanese]).","journal-title":"J. Jpn. Soc. Dial. Ther."},{"key":"58594_CR6","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1053\/j.ajkd.2020.05.025","volume":"77","author":"JJ Scialla","year":"2021","unstructured":"Scialla, J. J. et al. State-of-the-art management of hyperphosphatemia in patients with CKD: An NKF-KDOQI controversies perspective. Am. J. Kidney Dis. 77, 132\u2013141 (2021).","journal-title":"Am. J. Kidney Dis."},{"key":"58594_CR7","first-page":"555","volume":"95","author":"N Nagano","year":"2023","unstructured":"Nagano, N. et al. Combination therapy with multiple phosphate binders in hemodialysis patients: Limitations of phosphate binder therapy. Kidney Dial. 95, 555\u2013559 (2023) ([In Japanese]).","journal-title":"Kidney Dial."},{"key":"58594_CR8","first-page":"120","volume":"37","author":"K Ito","year":"2022","unstructured":"Ito, K. et al. How many dialysis patients want to reduce their phosphate binders, to what extent, and what benefits do they expect?. J. Jpn. Assoc. Dial. Phys. 37, 120\u2013128 (2022) ([In Japanese]).","journal-title":"J. Jpn. Assoc. Dial. Phys."},{"key":"58594_CR9","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aam6474","volume":"10","author":"AJ King","year":"2018","unstructured":"King, A. J. et al. Inhibition of sodium\/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. Sci. Transl. Med. 10, eaam6474 (2018).","journal-title":"Sci. Transl. Med."},{"key":"58594_CR10","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1053\/j.ajkd.2023.03.019","volume":"82","author":"M Fukagawa","year":"2023","unstructured":"Fukagawa, M. et al. Tenapanor for the treatment of hyperphosphatemia in japanese hemodialysis patients: A randomized phase 3 monotherapy study with an up-titration regimen. Am. J. Kidney Dis. 82, 635\u2013637 (2023).","journal-title":"Am. J. Kidney Dis."},{"key":"58594_CR11","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/s10157-023-02406-1","volume":"28","author":"M Nakayama","year":"2024","unstructured":"Nakayama, M. et al. Tenapanor for peritoneal dialysis patients with hyperphosphatemia: A phase 3 trial. Clin. Exp. Nephrol. 28, 153\u2013164 (2024).","journal-title":"Clin. Exp. Nephrol."},{"key":"58594_CR12","doi-asserted-by":"publisher","first-page":"2243","DOI":"10.1016\/j.ekir.2023.08.003","volume":"8","author":"K Nitta","year":"2023","unstructured":"Nitta, K. et al. Randomized study of tenapanor added to phosphate binders for patients with refractory hyperphosphatemia. Kidney Int. Rep. 8, 2243\u20132253 (2023).","journal-title":"Kidney Int. Rep."},{"key":"58594_CR13","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1111\/1744-9987.14241","volume":"29","author":"T Akizawa","year":"2025","unstructured":"Akizawa, T., Urano, N., Ikejiri, K., Nakanishi, K. & Fukagawa, M. Tenapanor: A novel therapeutic agent for dialysis patients with hyperphosphatemia. Ther. Apher. Dial. 29, 157\u2013169 (2025).","journal-title":"Ther. Apher. Dial."},{"key":"58594_CR14","doi-asserted-by":"publisher","first-page":"19100","DOI":"10.1038\/s41598-023-45080-9","volume":"13","author":"F Koiwa","year":"2023","unstructured":"Koiwa, F. et al. Long-term safety and decrease of pill burden by tenapanor therapy: A phase 3 open-label study in hemodialysis patients with hyperphosphatemia. Sci. Rep. 13, 19100 (2023).","journal-title":"Sci. Rep."},{"key":"58594_CR15","doi-asserted-by":"publisher","first-page":"732","DOI":"10.34067\/KID.0000000000000387","volume":"5","author":"SM Sprague","year":"2024","unstructured":"Sprague, S. M. et al. Tenapanor as therapy for hyperphosphatemia in maintenance dialysis patients: Results from the OPTIMIZE study. Kidney360 5, 732\u2013742 (2024).","journal-title":"Kidney360"},{"key":"58594_CR16","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.1093\/ndt\/gft280","volume":"29","author":"S Wang","year":"2014","unstructured":"Wang, S., Alfieri, T., Ramakrishnan, K., Braunhofer, P. & Newsome, B. A. Serum phosphorus levels and pill burden are inversely associated with adherence in patients on hemodialysis. Nephrol. Dial. Transplant. 29, 2092\u20132029 (2014).","journal-title":"Nephrol. Dial. Transplant."},{"key":"58594_CR17","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1111\/hdi.12315","volume":"20","author":"RB Fissell","year":"2016","unstructured":"Fissell, R. B. et al. Phosphate binder pill burden, patient-reported non-adherence, and mineral bone disorder markers: Findings from the DOPPS. Hemodial. Int. 20, 38\u201349 (2016).","journal-title":"Hemodial. 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Randomized crossover study of the efficacy and safety of sevelamer hydrochloride and lanthanum carbonate in Japanese patients undergoing hemodialysis. Ther. Apher. Dial. 16, 341\u2013349 (2012).","journal-title":"Ther. Apher. Dial."},{"key":"58594_CR21","doi-asserted-by":"crossref","unstructured":"Shigematsu, T.; Lanthanum Carbonate Group. Multicenter prospective randomized, double-blind comparative study between lanthanum carbonate and calcium carbonate as phosphate binders in Japanese hemodialysis patients with hyperphosphatemia. Clin. Nephrol. 70, 404\u2013410 (2008).","DOI":"10.5414\/CNP70404"},{"key":"58594_CR22","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1093\/ndt\/gft483","volume":"29","author":"K Yokoyama","year":"2014","unstructured":"Yokoyama, K. et al. A randomized trial of JTT-751 versus sevelamer hydrochloride in patients on hemodialysis. Nephrol. Dial. Transplant. 29, 1053\u20131060 (2014).","journal-title":"Nephrol. Dial. Transplant."},{"key":"58594_CR23","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1111\/1744-9987.12068","volume":"18","author":"T Akizawa","year":"2014","unstructured":"Akizawa, T. et al. Randomized controlled trial of bixalomer versus sevelamer hydrochloride in hemodialysis patients with hyperphosphatemia. Ther. Apher. Dial. 18, 122\u2013131 (2014).","journal-title":"Ther. Apher. Dial."},{"key":"58594_CR24","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1111\/nep.12891","volume":"22","author":"F Koiwa","year":"2017","unstructured":"Koiwa, F., Yokoyama, K., Fukagawa, M., Terao, A. & Akizawa, T. Efficacy and safety of sucroferric oxyhydroxide compared with sevelamer hydrochloride in Japanese haemodialysis patients with hyperphosphataemia: A randomized, open-label, multicentre, 12-week phase III study. Nephrology (Carlton). 22, 293\u2013300 (2017).","journal-title":"Nephrology (Carlton)."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-58594-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-58594-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-58594-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:11:23Z","timestamp":1790917883000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-58594-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["58594"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-58594-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"assertion":[{"value":"28 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Nobuo Nagano received consultancies from Kyowa Kirin Co., Ltd.; honoraria from Kyowa Kirin Co., Ltd.; Kissei Pharmaceutical Co., Ltd.; Toa Shinyaku Co., Ltd.; Nobelpharma Co., Ltd.; Torii Pharmaceutical Co., Ltd.; and Ono Pharmaceutical Co., Ltd. Shin Tokunaga and Shinji Asada are employees of Kyowa Kirin Co., Ltd. Masafumi Fukagawa received grants from Kyowa Kirin Co., Ltd. to his institution; consulting fees and honoraria from Sanwa Kagaku Kenkyusho Co., Ltd.; Ono Pharmaceutical Co., Ltd.; Kyowa Kirin Co., Ltd.; Bayer Yakuhin, Ltd.; Kissei Pharmaceutical Co., Ltd.; and Torii Pharmaceutical Co., Ltd. Tadao Akizawa received consulting fees from Kyowa Kirin Co., Ltd.; Kissei Pharmaceutical Co., Ltd.; Torii Pharmaceutical Co., Ltd.; and Sanwa Kagaku Kenkyusho Co., Ltd.; honoraria from Kyowa Kirin Co., Ltd.; Kissei Pharmaceutical Co., Ltd.; Ono Pharmaceutical Co., Ltd.; Torii Pharmaceutical Co., Ltd.; and Sanwa Kagaku Kenkyusho Co., Ltd.; support for travel fee from Kyowa Kirin Co., Ltd.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"30350"}}