{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:35:26Z","timestamp":1785818126043,"version":"3.56.0"},"reference-count":95,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Tenapanor, a selective inhibitor of the sodium\/hydrogen exchanger isoform 3 (NHE3), was initially developed for the treatment of irritable bowel syndrome with constipation. Subsequent preclinical and clinical studies revealed its ability to reduce gastrointestinal phosphate absorption, leading to effective serum phosphate control with minimal pill burden in patients with kidney failure undergoing dialysis therapy. However, the precise mechanisms underlying NHE3 inhibition, its impact on phosphate handling and the primary site of action within the gastrointestinal tract remain incompletely understood. This review explores the hypothesis that tenapanor-induced NHE3 inhibition elevates the luminal pH via enhanced bicarbonate secretion in the colon, thereby altering phosphate speciation. Phosphate exists in the body as monovalent (H\u2082PO\u2084\u207b) and divalent (HPO\u2084\u00b2\u207b) anions, with the latter predominating under alkaline conditions. Although divalent anions are theoretically more prone to be absorbed from the gut lumen via the paracellular transport route because of the lumen-negative transepithelial potential, on the contrary recent studies have provided evidence that monovalent species are transported more efficiently and that paracellular phosphate permeability is suppressed at high luminal pH. We now propose that the net negative electrostatic environment within the paracellular pore pathway of tight junctions may selectively hinder divalent phosphate transport. This hypothesis aligns with prior findings that tenapanor does not alter the expression of tight junction proteins, suggesting a physicochemical rather than a structural basis for reduced permeability. Further investigations are warranted to determine whether the electrostatic properties of the paracellular pathway contribute to the phosphate-lowering effect of tenapanor.<\/jats:p>","DOI":"10.1093\/ckj\/sfaf375","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T13:01:39Z","timestamp":1764421299000},"source":"Crossref","is-referenced-by-count":2,"title":["Mechanism of reduced intestinal phosphate absorption by tenapanor: a hypothesis"],"prefix":"10.1093","volume":"19","author":[{"given":"Takeshi","family":"Nakanishi","sequence":"first","affiliation":[{"name":"Hyogo Medical University Division of Kidney, Dialysis and Cardiology, Department of Internal Medicine, , Nishinomiya, Hyogo ,","place":["Japan"]},{"name":"Gojinkai Sumiyoshigawa Hospital Department of Nephrology, , Kobe, Hyogo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman B","family":"Drueke","sequence":"additional","affiliation":[{"name":"Inserm Unit 1018, Team 5, CESP, H\u00f4pital Paul Brousse, Paris-Saclay University (UPS) and Versailles Saint-Quentin-en-Yvelines University (UVSQ) , Villejuif ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6453-3824","authenticated-orcid":false,"given":"Takahiro","family":"Kuragano","sequence":"additional","affiliation":[{"name":"Hyogo Medical University Division of Kidney, Dialysis and Cardiology, Department of Internal Medicine, , Nishinomiya, Hyogo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"2026010506063982300_bib1","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1042\/CS20100377","article-title":"Phosphate toxicity: new insights into an old problem","volume":"120","author":"Razzaque","year":"2011","journal-title":"Clin Sci (Lond)"},{"key":"2026010506063982300_bib2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/978-3-030-91623-7_3","article-title":"Extracellular phosphate, inflammation and cytotoxicity","volume":"1362","author":"Michigami","year":"2022","journal-title":"Adv Exp Med Biol"},{"key":"2026010506063982300_bib3","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1016\/j.xkme.2021.07.003","article-title":"Phosphate absorption and hyperphosphatemia management in kidney disease: a physiology-based review","volume":"3","author":"Fishbane","year":"2021","journal-title":"Kidney Med"},{"key":"2026010506063982300_bib4","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1111\/1744-9987.12058","article-title":"Clinical practice guideline for the management of chronic kidney disease-mineral and bone disorder","volume":"17","author":"Fukagawa","year":"2013","journal-title":"Ther Apher Dial"},{"key":"2026010506063982300_bib5","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1053\/j.ajkd.2017.07.019","article-title":"KDOQI US commentary on the 2017 KDIGO clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD)","volume":"70","author":"Isakova","year":"2017","journal-title":"Am J Kidney Dis"},{"key":"2026010506063982300_bib6","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1053\/j.ajkd.2010.02.340","article-title":"KDOQI US commentary on the 2009 KDIGO Clinical practice guideline for the diagnosis, evaluation, and treatment of CKD-mineral and bone disorder (CKD-MBD)","volume":"55","author":"Uhlig","year":"2010","journal-title":"Am J Kidney Dis"},{"key":"2026010506063982300_bib7","doi-asserted-by":"publisher","first-page":"9457440","DOI":"10.1155\/2022\/9457440","article-title":"Phosphate frustration: treatment options to complement current therapies","volume":"2022","author":"Pergola","year":"2022","journal-title":"Int J Nephrol"},{"key":"2026010506063982300_bib8","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.2215\/CJN.00290109","article-title":"Pill burden, adherence, hyperphosphatemia, and quality of life in maintenance dialysis patients","volume":"4","author":"Chiu","year":"2009","journal-title":"Clin J Am Soc Nephrol"},{"key":"2026010506063982300_bib9","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1080\/17512433.2020.1762570","article-title":"Tenapanor for the treatment of irritable bowel syndrome with constipation","volume":"13","author":"Sinagra","year":"2020","journal-title":"Expert Rev Clin Pharmacol"},{"key":"2026010506063982300_bib10","doi-asserted-by":"publisher","first-page":"eaam6474","DOI":"10.1126\/scitranslmed.aam6474","article-title":"Inhibition of sodium\/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability","volume":"10","author":"King","year":"2018","journal-title":"Sci Transl Med"},{"key":"2026010506063982300_bib11","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1021\/acsmedchemlett.2c00037","article-title":"Discovery of tenapanor: a first-in-class minimally systemic inhibitor of intestinal Na+\/H+ exchanger isoform 3","volume":"13","author":"Jacobs","year":"2022","journal-title":"ACS Med Chem Lett"},{"key":"2026010506063982300_bib12","author":"Ogobuiro","year":"2023  8","journal-title":"Physiology, Gastrointestinal"},{"key":"2026010506063982300_bib13","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1146\/annurev.physiol.67.031103.153004","article-title":"Molecular physiology of intestinal Na+\/H+ exchange","volume":"67","author":"Zachos","year":"2005","journal-title":"Annu Rev Physiol"},{"key":"2026010506063982300_bib14","doi-asserted-by":"publisher","first-page":"9331","DOI":"10.1016\/S0021-9258(19)50428-8","article-title":"Molecular cloning of putative members of the Na\/H exchanger gene family. CDNA cloning, deduced amino acid sequence, and mRNA tissue expression of the rat Na\/H exchanger NHE-1 and two structurally related proteins","volume":"267","author":"Orlowski","year":"1992","journal-title":"J Biol Chem"},{"key":"2026010506063982300_bib15","doi-asserted-by":"publisher","first-page":"9340","DOI":"10.1016\/S0021-9258(19)50429-X","article-title":"Cloning and sequencing of a rabbit cDNA encoding an intestinal and kidney-specific Na+\/H+ exchanger isoform (NHE-3)","volume":"267","author":"Tse","year":"1992","journal-title":"J Biol Chem"},{"key":"2026010506063982300_bib16","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0016-5085(94)94837-2","article-title":"Na+ transport in human proximal colonic apical membrane vesicles","volume":"106","author":"Dudeja","year":"1994","journal-title":"Gastroenterology"},{"key":"2026010506063982300_bib17","first-page":"100591","article-title":"Inhibition of sodium-proton-exchanger subtype 3-mediated sodium absorption in the gut: a new antihypertensive concept","volume":"29","author":"Linz","year":"2020","journal-title":"Int J Cardiol Heart Vasc"},{"key":"2026010506063982300_bib18","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1161\/HYPERTENSIONAHA.112.201590","article-title":"Antihypertensive and laxative effects by pharmacological inhibition of sodium-proton-exchanger subtype 3-mediated sodium absorption in the gut","volume":"60","author":"Linz","year":"2012","journal-title":"Hypertension"},{"key":"2026010506063982300_bib19","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1681\/ASN.2014030317","article-title":"Gastrointestinal inhibition of sodium-hydrogen exchanger 3 reduces phosphorus absorption and protects against vascular calcification in CKD","volume":"26","author":"Labont\u00e9","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"2026010506063982300_bib20","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1007\/s40261-017-0614-0","article-title":"Pharmacodynamics, safety, and tolerability of the NHE3 inhibitor tenapanor: two trials in healthy volunteers","volume":"38","author":"Rosenbaum","year":"2018","journal-title":"Clin Drug Investig"},{"key":"2026010506063982300_bib21","doi-asserted-by":"publisher","first-page":"1933","DOI":"10.1681\/ASN.2016080855","article-title":"Effect of tenapanor on serum phosphate in patients receiving hemodialysis","volume":"28","author":"Block","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"2026010506063982300_bib22","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1111\/1744-9987.14241","article-title":"Tenapanor: a novel therapeutic agent for dialysis patients with hyperphosphatemia","volume":"29","author":"Akizawa","year":"2025","journal-title":"Ther Apher Dial"},{"key":"2026010506063982300_bib23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000546265","article-title":"Efficacy and safety of tenapanor in hemodialysis patients with hyperphosphatemia: a systematic review and meta-analysis of short term randomized control trails","volume":"9","author":"Khan","year":"2025","journal-title":"Am J Nephrol"},{"key":"2026010506063982300_bib24","doi-asserted-by":"publisher","first-page":"2371","DOI":"10.1016\/j.ekir.2021.06.030","article-title":"Effect of Tenapanor on phosphate binder pill burden in hemodialysis patients","volume":"6","author":"Akizawa","year":"2021","journal-title":"Kidney Int Rep"},{"key":"2026010506063982300_bib25","doi-asserted-by":"publisher","first-page":"e0319319","DOI":"10.1371\/journal.pone.0319319","article-title":"Efficacy of tenapanor in managing hyperphosphatemia and constipation in hemodialysis patients: a randomized controlled trial","volume":"20","author":"Suzuki","year":"2025","journal-title":"PLoS One"},{"key":"2026010506063982300_bib26","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1038\/969","article-title":"Renal and intestinal absorptive defects in mice lacking the NHE3 Na+\/H+ exchanger","volume":"19","author":"Schultheis","year":"1998","journal-title":"Nat Genet"},{"key":"2026010506063982300_bib27","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1042\/CS20200065","article-title":"An inducible intestinal epithelial cell-specific NHE3 knockout mouse model mimicking congenital sodium diarrhea","volume":"134","author":"Xue","year":"2020","journal-title":"Clin Sci (Lond)"},{"key":"2026010506063982300_bib28","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1172\/JCI1720","article-title":"Increased sensitivity to K+ deprivation in colonic H,K-ATPase-deficient mice","volume":"101","author":"Meneton","year":"1998","journal-title":"J Clin Invest"},{"key":"2026010506063982300_bib29","doi-asserted-by":"publisher","first-page":"1835","DOI":"10.1007\/s11255-024-04316-x","article-title":"Efficacy and safety of tenapanor vs placebo in treating CKD patients on dialysis and with hyperphosphatemia: a systematic review and meta-analysis of 2251 patients","volume":"57","author":"Abo Elnaga","year":"2025","journal-title":"Int Urol Nephrol"},{"key":"2026010506063982300_bib30","doi-asserted-by":"publisher","first-page":"G233","DOI":"10.1152\/ajpgi.00032.2019","article-title":"Paracellular transport of phosphate along the intestine","volume":"317","author":"Kn\u00f6pfel","year":"2019","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2026010506063982300_bib31","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1177\/1535370219831220","article-title":"Intestinal phosphate absorption: the paracellular pathway predominates?","volume":"244","author":"Saurette","year":"2019","journal-title":"Exp Biol Med (Maywood)"},{"key":"2026010506063982300_bib32","doi-asserted-by":"publisher","first-page":"e12281","DOI":"10.14814\/phy2.12281","article-title":"Experimental and regional variations in Na+-dependent and Na+-independent phosphate transport along the rat small intestine and colon","volume":"3","author":"Marks","year":"2015","journal-title":"Physiol Rep"},{"key":"2026010506063982300_bib33","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1093\/ndt\/gfad188","article-title":"The basics of phosphate metabolism","volume":"39","author":"Wagner","year":"2024","journal-title":"Nephrol Dial Transplant"},{"key":"2026010506063982300_bib34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1152\/physrev.00008.2019","article-title":"Phosphate transport in epithelial and nonepithelial tissue","volume":"101","author":"Hernando","year":"2021","journal-title":"Physiol Rev"},{"key":"2026010506063982300_bib35","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1159\/000107069","article-title":"New aspect of renal phosphate reabsorption: the type IIc sodium-dependent phosphate transporter","volume":"27","author":"Miyamoto","year":"2007","journal-title":"Am J Nephrol"},{"key":"2026010506063982300_bib36","doi-asserted-by":"publisher","first-page":"F643","DOI":"10.1152\/ajprenal.00228.2007","article-title":"Phosphate transporters: a tale of two solute carrier families","volume":"293","author":"Virkki","year":"2007","journal-title":"Am J Physiol Renal Physiol"},{"key":"2026010506063982300_bib37","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1053\/j.ackd.2010.11.004","article-title":"Intestinal phosphate transport","volume":"18","author":"Sabbagh","year":"2011","journal-title":"Adv Chronic Kidney Dis"},{"key":"2026010506063982300_bib38","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1093\/ndt\/gfaa156","article-title":"Evidence of an intestinal phosphate transporter alternative to type IIb sodium-dependent phosphate transporter in rats with chronic kidney disease","volume":"36","author":"Ichida","year":"2021","journal-title":"Nephrol Dial Transplant"},{"key":"2026010506063982300_bib39","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/s00232-006-0016-3","article-title":"Electrogenic kinetics of a mammalian intestinal type IIb Na(+)\/P(i) cotransporter","volume":"212","author":"Forster","year":"2006","journal-title":"J Membrane Biol"},{"key":"2026010506063982300_bib40","doi-asserted-by":"publisher","first-page":"14564","DOI":"10.1073\/pnas.95.24.14564","article-title":"Characterization of a murine type II sodium-phosphate cotransporter expressed in mammalian small intestine","volume":"95","author":"Hilfiker","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026010506063982300_bib41","doi-asserted-by":"publisher","first-page":"jcs261776","DOI":"10.1242\/jcs.261776","article-title":"A short guide to the tight junction","volume":"137","author":"Citi","year":"2024","journal-title":"J Cell Sci"},{"key":"2026010506063982300_bib42","doi-asserted-by":"publisher","first-page":"183279","DOI":"10.1016\/j.bbamem.2020.183279","article-title":"Molecular architecture and assembly of the tight junction backbone","volume":"1862","author":"Piontek","year":"2020","journal-title":"Biochim Biophys Acta Biomembr"},{"key":"2026010506063982300_bib43","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1038\/nrm.2016.80","article-title":"Tight junctions: from simple barriers to multifunctional molecular gates","volume":"17","author":"Zihni","year":"2016","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2026010506063982300_bib44","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1091\/mbc.e16-10-0698","article-title":"Visualizing the dynamic coupling of claudin strands to the actin cytoskeleton through ZO-1","volume":"28","author":"Van Itallie","year":"2017","journal-title":"Mol Biol Cell"},{"key":"2026010506063982300_bib45","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1016\/0016-5085(83)90443-2","article-title":"Absorption of phosphate in the jejunum of patients with chronic renal failure before and after correction of vitamin D deficiency","volume":"85","author":"Davis","year":"1983","journal-title":"Gastroenterology"},{"key":"2026010506063982300_bib46","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s10157-017-1497-3","article-title":"Effect of Npt2b deletion on intestinal and renal inorganic phosphate (Pi) handling","volume":"22","author":"Ikuta","year":"2018","journal-title":"Clin Exp Nephrol"},{"key":"2026010506063982300_bib47","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1136\/gut.10.6.418","article-title":"Electric-potential difference\u2014a neglected parameter of gut integrity and function?","volume":"10","author":"Geall","year":"1969","journal-title":"Gut"},{"key":"2026010506063982300_bib48","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/S0169-409X(00)00046-6","article-title":"Show me the pathway! regulation of paracellular permeability by Na(+)-glucose cotransport","volume":"41","author":"Turner","year":"2000","journal-title":"Adv Drug Deliv Rev"},{"key":"2026010506063982300_bib49","first-page":"238080","article-title":"Mechanisms of the regulation of the intestinal Na+\/H+ exchanger NHE3","author":"He","year":"2010","journal-title":"J Biomed Biotechnol"},{"key":"2026010506063982300_bib50","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/s41575-023-00766-3","article-title":"Paracellular permeability and tight junction regulation in gut health and disease","volume":"20","author":"Horowitz","year":"2023","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2026010506063982300_bib51","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1053\/j.gastro.2008.07.083","article-title":"Down-regulated in adenoma Cl\/HCO3 exchanger couples with Na\/H exchanger 3 for NaCl absorption in murine small intestine","volume":"135","author":"Walker","year":"2008","journal-title":"Gastroenterology"},{"key":"2026010506063982300_bib52","doi-asserted-by":"publisher","first-page":"G102","DOI":"10.1152\/ajpgi.00092.2003","article-title":"NHE3 inhibition activates duodenal bicarbonate secretion in the rat","volume":"286","author":"Furukawa","year":"2004","journal-title":"Am J Physiol Gastrointestinal and Liver Physiol"},{"key":"2026010506063982300_bib53","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1177\/2211068214561025","article-title":"TEER measurement techniques for in vitro barrier model systems","volume":"20","author":"Srinivasan","year":"2015","journal-title":"J Lab Autom"},{"key":"2026010506063982300_bib54","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/nrm1055","article-title":"Signalling to and from tight junctions","volume":"4","author":"Matter","year":"2003","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2026010506063982300_bib55","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1083\/jcb.134.4.1031","article-title":"Functional dissociation of paracellular permeability and transepithelial electrical resistance and disruption of the apical-basolateral intramembrane diffusion barrier by expression of a mutant tight junction membrane protein","volume":"134","author":"Balda","year":"1996","journal-title":"J Cell Biol"},{"key":"2026010506063982300_bib56","doi-asserted-by":"publisher","first-page":"G197","DOI":"10.1152\/ajpgi.2000.278.2.G197","article-title":"NHE1, NHE2, and NHE3 contribute to regulation of intracellular pH in murine duodenal epithelial cells","volume":"278","author":"Praetorius","year":"2000","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2026010506063982300_bib57","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.33594\/000000070","article-title":"Expression, localization and functional activity of the major Na+\/H+ exchange isoforms expressed in the intestinal cell line Caco-2BBe","volume":"52","author":"Yu","year":"2019","journal-title":"Cell Physiol Biochem"},{"key":"2026010506063982300_bib58","doi-asserted-by":"publisher","first-page":"2189","DOI":"10.1113\/jphysiol.2012.247874","article-title":"Essential role of the electroneutral Na+-HCO3- cotransporter NBCn1 in murine duodenal acid-base balance and colonic mucus layer build-up in vivo","volume":"591","author":"Singh","year":"2013","journal-title":"J Physiol"},{"key":"2026010506063982300_bib59","doi-asserted-by":"publisher","first-page":"C1625","DOI":"10.1152\/ajpcell.00079.2024","article-title":"The electroneutral Na(+)-HCO(3)(-) cotransporter NBCn1 (SLC4A7) modulates colonic enterocyte pH(i), proliferation, and migration","volume":"326","author":"Jiang","year":"2024","journal-title":"Am J Physiol Cell Physiol"},{"key":"2026010506063982300_bib60","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1007\/s00424-024-02914-3","article-title":"Bicarbonate secretion and acid\/base sensing by the intestine","volume":"476","author":"Becker","year":"2024","journal-title":"Pflugers Arch"},{"key":"2026010506063982300_bib61","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.tcb.2009.12.002","article-title":"Dynamics and functions of tight junctions","volume":"20","author":"Steed","year":"2010","journal-title":"Trends Cell Biol"},{"key":"2026010506063982300_bib62","doi-asserted-by":"publisher","first-page":"C829","DOI":"10.1152\/ajpcell.00590.2023","article-title":"Reduced surface pH and upregulated AE2 anion exchange in SLC26A3-deleted polarized intestinal epithelial cells","volume":"326","author":"Amiri","year":"2024","journal-title":"Am J Physiol Cell Physiol"},{"key":"2026010506063982300_bib63","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1111\/bph.15323","article-title":"Inhibition of Na+\/H+ exchanger isoform 3 improves gut fluidity and alkalinity in cystic fibrosis transmembrane conductance regulator-deficient and F508del mutant mice","volume":"178","author":"Tan","year":"2021","journal-title":"Br J Pharmacol"},{"key":"2026010506063982300_bib64","doi-asserted-by":"publisher","first-page":"G159","DOI":"10.1152\/ajpgi.2001.281.1.G159","article-title":"Human duodenal mucosal brush border Na(+)\/H(+) exchangers NHE2 and NHE3 alter net bicarbonate movement","volume":"281","author":"Repishti","year":"2001","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2026010506063982300_bib65","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s00223-020-00686-3","article-title":"Phosphate metabolism in health and disease","volume":"108","author":"Peacock","year":"2021","journal-title":"Calcif Tissue Int"},{"key":"2026010506063982300_bib66","doi-asserted-by":"publisher","first-page":"C142","DOI":"10.1152\/ajpcell.00038.2002","article-title":"Claudins create charge-selective channels in the paracellular pathway between epithelial cells","volume":"283","author":"Colegio","year":"2002","journal-title":"Am J Physiol Cell Physiol"},{"key":"2026010506063982300_bib67","doi-asserted-by":"publisher","first-page":"a002584","DOI":"10.1101\/cshperspect.a002584","article-title":"Physiology and function of the tight junction","volume":"1","author":"Anderson","year":"2009","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"2026010506063982300_bib68","doi-asserted-by":"publisher","first-page":"6214","DOI":"10.1038\/s41467-023-41999-9","article-title":"Claudin-23 reshapes epithelial tight junction architecture to regulate barrier function","volume":"14","author":"Raya-Sandino","year":"2023","journal-title":"Nat Commun"},{"key":"2026010506063982300_bib69","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1016\/j.xphs.2021.12.005","article-title":"Studies on the pH-dependent solubility of various grades of calcium phosphate-based pharmaceutical excipients","volume":"111","author":"Wagner","year":"2022","journal-title":"J Pharm Sci"},{"key":"2026010506063982300_bib70","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1093\/jn\/122.3.580","article-title":"Interaction of calcium and phosphate decreases ileal magnesium solubility and apparent magnesium absorption in rats","volume":"122","author":"Brink","year":"1992","journal-title":"J Nutr"},{"key":"2026010506063982300_bib71","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1002\/j.2040-4603.2018.tb00031.x","article-title":"Mechanisms and regulation of intestinal phosphate absorption","volume":"8","author":"Hernando","year":"2018","journal-title":"Compr Physiol"},{"key":"2026010506063982300_bib72","author":"Barrett","year":"2010","journal-title":"Ganong\u2019s Review of Medical Physiology"},{"key":"2026010506063982300_bib73","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/0009-8981(77)90398-9","article-title":"Inorganic phosphorus in human bile","volume":"77","author":"Sutor","year":"1977","journal-title":"Clin Chim Acta"},{"key":"2026010506063982300_bib74","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1007\/BF01951707","article-title":"Role of inorganic phosphate in total biliary phosphorus determination","volume":"41","author":"Jones","year":"1985","journal-title":"Experientia"},{"key":"2026010506063982300_bib75","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/0009-8981(78)90374-1","article-title":"Inorganic phosphate in bile and \u2018bile-rich\u2019 duodenal aspirates","volume":"89","author":"Wiegard","year":"1978","journal-title":"Clin Chim Acta"},{"key":"2026010506063982300_bib76","first-page":"2100","article-title":"[Changes of inorganic phosphorus concentration in the pancreatic juice of dogs with experimental acute pancreatitis\u2014comparison with histological findings.]","volume":"82","author":"Akashi","year":"1985","journal-title":"Nihon Shokakibyo Gakkai Zasshi"},{"key":"2026010506063982300_bib77","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1079\/BJN19830049","article-title":"Studies on gastric digestion of protein and carbohydrate, gastric secretion and exocrine pancreatic secretion in the growing pig","volume":"49","author":"Zebrowska","year":"1983","journal-title":"Br J Nutr"},{"key":"2026010506063982300_bib78","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/978-1-4684-7758-0_16","article-title":"Intestinal inorganic phosphate transport","volume":"103","author":"Walling","year":"1978","journal-title":"Adv Exp Med Biol"},{"key":"2026010506063982300_bib79","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1159\/000518110","article-title":"Small intestinal phosphate absorption: novel therapeutic implications","volume":"52","author":"Yee","year":"2021","journal-title":"Am J Nephrol"},{"key":"2026010506063982300_bib80","doi-asserted-by":"publisher","first-page":"2388","DOI":"10.1093\/jn\/131.9.2388","article-title":"Novel methodology allows simultaneous measurement of true phosphorus digestibility and the gastrointestinal endogenous phosphorus outputs in studies with pigs","volume":"131","author":"Fan","year":"2001","journal-title":"J Nutr"},{"key":"2026010506063982300_bib81","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1146\/annurev.physiol.67.031103.153530","article-title":"Secretion and absorption by colonic crypts","volume":"67","author":"Geibel","year":"2005","journal-title":"Annu Rev Physiol"},{"key":"2026010506063982300_bib82","first-page":"7","article-title":"Paracellular phosphate absorption in rat colon: a mechanism for enema-induced hyperphosphatemia","volume":"23","author":"Hu","year":"1997","journal-title":"Miner Electrolyte Metab"},{"key":"2026010506063982300_bib83","first-page":"929","article-title":"Fatal hyperphosphatemia following Fleet Phospo-Soda in a patient with colonic ileus","volume":"88","author":"Fass","year":"1993","journal-title":"Am J Gastroenterol"},{"key":"2026010506063982300_bib84","doi-asserted-by":"publisher","first-page":"e13756","DOI":"10.1111\/apha.13756","article-title":"Enhanced phosphate absorption in intestinal epithelial cell-specific NHE3 knockout mice","volume":"234","author":"Xue","year":"2022","journal-title":"Acta Physiol (Oxf)"},{"key":"2026010506063982300_bib85","doi-asserted-by":"publisher","first-page":"S53","DOI":"10.1097\/01.mcg.0000155521.81382.3a","article-title":"Bicarbonate secretion: a neglected aspect of colonic ion transport","volume":"39","author":"Binder","year":"2005","journal-title":"J Clin Gastroenterol"},{"key":"2026010506063982300_bib86","doi-asserted-by":"publisher","first-page":"G358","DOI":"10.1152\/ajpgi.00151.2010","article-title":"Segregation of Na\/H exchanger-3 and Cl\/HCO3 exchanger SLC26A3 (DRA) in rodent cecum and colon","volume":"299","author":"Talbot","year":"2010","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2026010506063982300_bib87","doi-asserted-by":"publisher","first-page":"22855","DOI":"10.1074\/jbc.274.32.22855","article-title":"Mouse down-regulated in adenoma (DRA) is an intestinal Cl(-)\/HCO(3)(-) exchanger and is up-regulated in colon of mice lacking the NHE3 Na(+)\/H(+) exchanger","volume":"274","author":"Melvin","year":"1999","journal-title":"J Biol Chem"},{"key":"2026010506063982300_bib88","doi-asserted-by":"publisher","first-page":"11897","DOI":"10.1074\/jbc.270.20.11897","article-title":"The down regulated in Adenoma (dra) gene encodes an intestine-specific membrane sulfate transport protein","volume":"270","author":"Silberg","year":"1995","journal-title":"J Biol Chem"},{"key":"2026010506063982300_bib89","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/ng1196-316","article-title":"Mutations of the down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea","volume":"14","author":"H\u00f6glund","year":"1996","journal-title":"Nat Genet"},{"key":"2026010506063982300_bib90","doi-asserted-by":"publisher","first-page":"G573","DOI":"10.1152\/ajpgi.00338.2001","article-title":"Identification of an apical Cl(-)\/HCO3(-) exchanger in the small intestine","volume":"282","author":"Wang","year":"2002","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2026010506063982300_bib91","first-page":"G825","article-title":"Base secretion in rat distal colon: ionic requirements","volume":"258","author":"Feldman","year":"1990","journal-title":"Am J Physiol"},{"key":"2026010506063982300_bib92","doi-asserted-by":"publisher","first-page":"C35","DOI":"10.1152\/ajpcell.1990.259.1.C35","article-title":"H+ and HCO3\u2212 flux across apical surface of rat distal colon","volume":"259","author":"Feldman","year":"1990","journal-title":"Am J Physiol Cell Physiol"},{"key":"2026010506063982300_bib93","doi-asserted-by":"publisher","first-page":"15","DOI":"10.2220\/biomedres.27.15","article-title":"Chloride-dependent bicarbonate secretion in the mouse large intestine","volume":"27","author":"Kawamata","year":"2006","journal-title":"Biomed Res"},{"key":"2026010506063982300_bib94","doi-asserted-by":"publisher","first-page":"C612","DOI":"10.1152\/ajpcell.00474.2003","article-title":"Three distinct mechanisms of HCO3\u2212 secretion in rat distal colon","volume":"287","author":"Vidyasagar","year":"2004","journal-title":"Am J Physiol Cell Physiol"},{"key":"2026010506063982300_bib95","doi-asserted-by":"publisher","first-page":"G63","DOI":"10.1152\/ajpgi.90207.2008","article-title":"Colonic gene expression profile in NHE3-deficient mice: evidence for spontaneous distal colitis","volume":"295","author":"Laubitz","year":"2008","journal-title":"Am J Physiol Gastrointest Liver Physiol"}],"container-title":["Clinical Kidney Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ckj\/advance-article-pdf\/doi\/10.1093\/ckj\/sfaf375\/65665055\/sfaf375.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ckj\/article-pdf\/19\/1\/sfaf375\/65665055\/sfaf375.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ckj\/article-pdf\/19\/1\/sfaf375\/65665055\/sfaf375.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T11:06:45Z","timestamp":1767611205000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ckj\/article\/doi\/10.1093\/ckj\/sfaf375\/8362041"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,1]]},"references-count":95,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,2]]}},"URL":"https:\/\/doi.org\/10.1093\/ckj\/sfaf375","relation":{},"ISSN":["2048-8505","2048-8513"],"issn-type":[{"value":"2048-8505","type":"print"},{"value":"2048-8513","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2025,12,1]]},"article-number":"sfaf375"}}