{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T21:41:25Z","timestamp":1790890885496,"version":"4.1.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004095","name":"Kyowa Hakko 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":["Clin Exp Nephrol"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Tenapanor is a novel selective inhibitor of intestinal sodium\/hydrogen exchanger 3 transporter. This is the first trial to assess the efficacy and safety of tenapanor in Japanese patients with hyperphosphatemia who are undergoing peritoneal dialysis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This phase 3, open-label, multicenter, single-arm clinical trial targeted patients whose serum phosphorus was within 3.5\u20137.0 mg\/dL with phosphate binders at screening. After phosphate binder washout, tenapanor was orally administered twice-daily, stepwise from 5 to 30 mg\/dose for 16 weeks. The primary endpoint, mean change in serum phosphorus level, was evaluated at week 8. The 16-week treatment period was completed with tenapanor alone, and only one phosphate binder type was allowed for combined use after the primary endpoint.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Of the 54 patients enrolled, 34 completed the study. At week 8, the primary endpoint, mean change in serum phosphorus level (last observation carried forward), was\u2009\u2212\u20091.18 mg\/dL (95% confidence interval:\u2009\u2212\u20091.54,\u2009\u2212\u20090.81\u00a0mg\/dL) with tenapanor. From a baseline value of 7.65 mg\/dL, serum phosphorus decreased to 6.14 and 5.44 mg\/dL at weeks 8 and 16, respectively, and 46.3% and 76.5% of patients achieved serum phosphorus within 3.5\u20136.0 mg\/dL at week 8 and week 16, respectively. The most common adverse event, diarrhea, occurred in 74.1% of patients; the severity of diarrhea was mild or moderate. Thus, the discontinuation percentage due to diarrhea was low at 5.6%.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Administration of tenapanor resulted in a sufficient reduction in serum phosphorus level at week 8 and was considered safe and tolerable.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>NCT04766385.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10157-023-02406-1","type":"journal-article","created":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T10:02:06Z","timestamp":1698832926000},"page":"153-164","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Tenapanor for peritoneal dialysis patients with hyperphosphatemia: a phase 3 trial"],"prefix":"10.1007","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7686-8899","authenticated-orcid":false,"given":"Masaaki","family":"Nakayama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Kusakabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiko","family":"Ohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Nakanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadao","family":"Akizawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Fukagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,1]]},"reference":[{"key":"2406_CR1","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/S0140-6736(20)30045-3","volume":"395","author":"GBD Chronic Kidney Disease Collaboration","year":"2020","unstructured":"GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395:709\u201333.","journal-title":"Lancet"},{"key":"2406_CR2","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.jsps.2015.01.009","volume":"24","author":"AM Shaman","year":"2016","unstructured":"Shaman AM, Kowalski SR. Hyperphosphatemia management in patients with chronic kidney disease. Saudi Pharm J. 2016;24:494\u2013505.","journal-title":"Saudi Pharm J"},{"key":"2406_CR3","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1159\/000452880","volume":"3","author":"X Lu","year":"2017","unstructured":"Lu X, Hu MC. Klotho\/FGF23 axis in chronic kidney disease and cardiovascular disease. Kidney Dis (Basel). 2017;3:15\u201323.","journal-title":"Kidney Dis (Basel)"},{"key":"2406_CR4","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/nrneph.2010.68","volume":"6","author":"RT Krediet","year":"2010","unstructured":"Krediet RT, Balafa O. Cardiovascular risk in the peritoneal dialysis patient. Nat Rev Nephrol. 2010;6:451\u201360.","journal-title":"Nat Rev Nephrol"},{"key":"2406_CR5","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/sj.ki.5001542","volume":"70","author":"ML Melamed","year":"2006","unstructured":"Melamed ML, Eustace JA, Plantinga L, Jaar BG, Fink NE, Coresh J, et al. Changes in serum calcium, phosphate, and PTH and the risk of death in incident dialysis patients: a longitudinal study. Kidney Int. 2006;70:351\u20137.","journal-title":"Kidney Int"},{"key":"2406_CR6","doi-asserted-by":"publisher","first-page":"2513","DOI":"10.1093\/ndt\/gfl257","volume":"21","author":"M Noordzij","year":"2006","unstructured":"Noordzij M, Korevaar JC, Bos WJ, Boeschoten EW, Dekker FW, Bossuyt PM, et al. Mineral metabolism and cardiovascular morbidity and mortality risk: peritoneal dialysis patients compared with haemodialysis patients. Nephrol Dial Transplant. 2006;21:2513\u201320.","journal-title":"Nephrol Dial Transplant"},{"issue":"4 Suppl 3","key":"2406_CR7","first-page":"S1V201","volume":"42","author":"National Kidney Foundation","year":"2003","unstructured":"National Kidney Foundation. K\/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(4 Suppl 3):S1V201.","journal-title":"Am J Kidney Dis"},{"key":"2406_CR8","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1111\/1744-9987.12058","volume":"17","author":"M Fukagawa","year":"2013","unstructured":"Fukagawa M, Yokoyama K, Koiwa F, Taniguchi M, Shoji T, Kazama JJ, et al. Clinical practice guideline for the management of chronic kidney disease-mineral and bone disorder. Ther Apher Dial. 2013;17:247\u201388.","journal-title":"Ther Apher Dial"},{"key":"2406_CR9","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.2215\/CJN.00290109","volume":"4","author":"YW Chiu","year":"2009","unstructured":"Chiu YW, Teitelbaum I, Misra M, de Leon EM, Adzize T, Mehrotra R. Pill burden, adherence, hyperphosphatemia, and quality of life in maintenance dialysis patients. Clin J Am Soc Nephrol. 2009;4:1089\u201396.","journal-title":"Clin J Am Soc Nephrol"},{"key":"2406_CR10","doi-asserted-by":"publisher","first-page":"31","DOI":"10.3747\/pdi.2013.00129","volume":"35","author":"B Evsanaa","year":"2015","unstructured":"Evsanaa B, Liu I, Aliazardeh B, Mahdavi S, Bajwa G, Gula J, et al. MgCaCO3 versus CaCO3 in peritoneal dialysis patients\u2014a cross-over pilot trial. Perit Dial Int. 2015;35:31\u20134.","journal-title":"Perit Dial Int"},{"key":"2406_CR11","doi-asserted-by":"publisher","first-page":"1918","DOI":"10.1093\/ndt\/gfw460","volume":"32","author":"J Floege","year":"2017","unstructured":"Floege J, Covic AC, Ketteler M, Mann J, Rastogi A, Spinowitz B, et al. One-year efficacy and safety of the iron-based phosphate binder sucroferric oxyhydroxide in patients on peritoneal dialysis. Nephrol Dial Transplant. 2017;32:1918\u201326.","journal-title":"Nephrol Dial Transplant"},{"key":"2406_CR12","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1111\/j.1744-9987.2012.01098.x","volume":"17","author":"KY Hung","year":"2013","unstructured":"Hung KY, Liao SC, Chen TH, Chao MC, Chen JB. Adherence to phosphate binder therapy is the primary determinant of hyperphosphatemia incidence in patients receiving peritoneal dialysis. Ther Apher Dial. 2013;17:72\u20137.","journal-title":"Ther Apher Dial"},{"key":"2406_CR13","doi-asserted-by":"publisher","first-page":"227ra36","DOI":"10.1126\/scitranslmed.3007790","volume":"6","author":"AG Spencer","year":"2014","unstructured":"Spencer AG, Labonte ED, Rosenbaum DP, Plato CF, Carreras CW, Leadbetter MR, et al. Intestinal inhibition of the Na+\/H+ exchanger 3 prevents cardiorenal damage in rats and inhibits Na+ uptake in humans. Sci Transl Med. 2014;6:227ra36.","journal-title":"Sci Transl Med."},{"key":"2406_CR14","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1681\/ASN.2014030317","volume":"26","author":"ED Labont\u00e9","year":"2015","unstructured":"Labont\u00e9 ED, Carreras CW, Leadbetter MR, Kozuka K, Kohler J, Koo-McCoy S, et al. Gastrointestinal inhibition of sodium-hydrogen exchanger 3 reduces phosphorus absorption and protects against vascular calcification in CKD. J Am Soc Nephrol. 2015;26:1138\u201349.","journal-title":"J Am Soc Nephrol"},{"key":"2406_CR15","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1681\/ASN.2018080832","volume":"30","author":"GA Block","year":"2019","unstructured":"Block GA, Rosenbaum DP, Yan A, Chertow GM. Efficacy and safety of tenapanor in patients with hyperphosphatemia receiving maintenance hemodialysis: a randomized phase 3 trial. J Am Soc Nephrol. 2019;30:641\u201352.","journal-title":"J Am Soc Nephrol"},{"key":"2406_CR16","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.ekir.2021.11.008","volume":"7","author":"M Inaba","year":"2021","unstructured":"Inaba M, Une Y, Ikejiri K, Kanda H, Fukagawa M, Akizawa T, et al. Dose-response of tenapanor in patients with hyperphosphatemia undergoing hemodialysis in Japan\u2014a phase 2 randomized trial. Kidney Int Rep. 2021;7:177\u201388.","journal-title":"Kidney Int Rep"},{"key":"2406_CR17","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.34067\/KID.0002002021","volume":"2","author":"GA Block","year":"2021","unstructured":"Block GA, Bleyer AJ, Silva AL, et al. Safety and efficacy of tenapanor for long-term serum phosphate control in maintenance dialysis: a 52-week randomized phase 3 trial (PHREEDOM). Kidney360. 2021;2:1600\u201310.","journal-title":"Kidney360."},{"key":"2406_CR18","doi-asserted-by":"publisher","unstructured":"Fukagawa M, Urano N, Ikejiri K, Kinoshita J, Nakanishi K, Akizawa T, 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. 2023. https:\/\/doi.org\/10.1053\/j.ajkd.2023.03.019","DOI":"10.1053\/j.ajkd.2023.03.019"},{"key":"2406_CR19","doi-asserted-by":"publisher","first-page":"2511","DOI":"10.1681\/ASN.V12112511","volume":"12","author":"M Cozzolino","year":"2001","unstructured":"Cozzolino M, Dusso AS, Slatopolsky E. Role of calcium-phosphate product and bone-associated proteins on vascular calcification in renal failure. J Am Soc Nephrol. 2001;12:2511\u20136.","journal-title":"J Am Soc Nephrol"},{"key":"2406_CR20","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1053\/ajkd.1998.v31.pm9531176","volume":"31","author":"GA Block","year":"1998","unstructured":"Block GA, Hulbert-Shearon TE, Levin NW, Port FK. Association of serum phosphorus and calcium \u00d7 phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis. 1998;31:607\u201317.","journal-title":"Am J Kidney Dis"},{"key":"2406_CR21","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1097\/00041552-200109000-00003","volume":"10","author":"NW Levin","year":"2001","unstructured":"Levin NW, Hoenich NA. Consequences of hyperphosphatemia and elevated levels of the calcium-phosphorus product in dialysis patients. Curr Opin Nephrol Hypertens. 2001;10:563\u20138.","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"2406_CR22","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.atherosclerosis.2018.08.046","volume":"278","author":"AB Reiss","year":"2018","unstructured":"Reiss AB, Miyawaki N, Moon J, Kasselman LJ, Voloshyna I, D\u2019Avino R Jr, et al. CKD, arterial calcification, atherosclerosis and bone health: inter-relationships and controversies. Atherosclerosis. 2018;278:49\u201359.","journal-title":"Atherosclerosis"},{"key":"2406_CR23","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1159\/000366482","volume":"128","author":"K Yokoyama","year":"2014","unstructured":"Yokoyama K, Akiba T, Fukagawa M, Nakayama M, Hirakata H. JTT-751 for treatment of patients with hyperphosphatemia on peritoneal dialysis. Nephron Clin Pract. 2014;128:135\u201340.","journal-title":"Nephron Clin Pract"},{"key":"2406_CR24","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1177\/089686080802800622","volume":"28","author":"H Kawanishi","year":"2008","unstructured":"Kawanishi H, Ishida M, Ishizaki M, Takuma Y, Tamura H, Kobayashi S, et al. Lanthanum carbonate treatment of patients with hyperphosphatemia undergoing CAPD. Perit Dial Int. 2008;28:673\u20135.","journal-title":"Perit Dial Int"}],"container-title":["Clinical and Experimental Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10157-023-02406-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10157-023-02406-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10157-023-02406-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T01:11:34Z","timestamp":1706145094000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10157-023-02406-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,1]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["2406"],"URL":"https:\/\/doi.org\/10.1007\/s10157-023-02406-1","relation":{},"ISSN":["1342-1751","1437-7799"],"issn-type":[{"value":"1342-1751","type":"print"},{"value":"1437-7799","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,1]]},"assertion":[{"value":"3 April 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 November 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"M.N. received lecture fees from Kyowa Kirin. S.K., M.K., M.O., and K.N. are employees of Kyowa Kirin Co., Ltd. T.A. received consulting fees from Kyowa Kirin, Kissei Pharmaceutical, Ono Pharmaceutical, Torii Pharmaceutical, Astellas, Bayer Japan, Sanwa Kagaku, and received lecture fees from Kyowa Kirin, Kissei Pharmaceutical, Ono Pharmaceutical, Torii Pharmaceutical, Astellas, Bayer Japan, and Sanwa Kagaku. M.F. received consulting fees from Sanwa Kagaku and Ono Pharmaceutical, and received lecture fees from Kyowa Kirin, Bayer Japan, and Kissei Pharmaceutical.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}