{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:28:01Z","timestamp":1790141281674,"version":"4.0.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,6,26]],"date-time":"2020-06-26T00:00:00Z","timestamp":1593129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,26]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Sodium zirconium cyclosilicate (SZC) binds potassium and ammonium in the gastrointestinal tract. In addition to serum potassium reduction, Phase 2 trial data have shown increased serum bicarbonate with SZC, which may be clinically beneficial because maintaining serum bicarbonate \u226522\u2009mmol\/L preserves kidney function. This exploratory analysis examined serum bicarbonate and urea, and urine pH data from three SZC randomized, placebo-controlled Phase 3 studies among patients with hyperkalaemia [ZS-003 (n\u2009=\u2009753), HARMONIZE (n\u2009=\u2009258) and HARMONIZE-Global (n\u2009=\u2009267)].<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In all studies, patients received \u226410\u2009g SZC 3 times daily (TID) for 48\u2009h to correct hyperkalaemia, followed by randomization to maintenance therapy with SZC once daily (QD) versus placebo for \u226429\u2009days among those achieving normokalaemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significant dose-dependent mean serum bicarbonate increases from baseline of 0.3 to 1.5\u2009mmol\/L occurred within 48\u2009h of SZC TID in ZS-003 (all P\u2009&amp;lt;\u20090.05), which occurred regardless of chronic kidney disease (CKD) stage. Similar acute increases in HARMONIZE and HARMONIZE-Global were maintained over 29\u2009days. With highest SZC maintenance doses, patient proportions with serum bicarbonate &amp;lt;22\u2009mmol\/L fell from 39.4% at baseline to 4.9% at 29\u2009days (P\u2009=\u20090.005) in HARMONIZE and from 87.9% to 70.1%, (P\u2009=\u20090.006) in HARMONIZE-Global. Path analyses demonstrated that serum urea decreases (but not serum potassium or urine pH changes) were associated with SZC effects on serum bicarbonate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>SZC increased serum bicarbonate concentrations and reduced patient proportions with serum bicarbonate &amp;lt;22\u2009mmol\/L, likely due to SZC-binding of gastrointestinal ammonium. These SZC-induced serum bicarbonate increases occurred regardless of CKD stage and were sustained during ongoing maintenance therapy.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ndt\/gfaa158","type":"journal-article","created":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T11:11:52Z","timestamp":1591182712000},"page":"871-883","source":"Crossref","is-referenced-by-count":23,"title":["Sodium zirconium cyclosilicate increases serum bicarbonate concentrations among patients with hyperkalaemia: exploratory analyses from three randomized, multi-dose, placebo-controlled trials"],"prefix":"10.1093","volume":"36","author":[{"given":"Simon D","family":"Roger","sequence":"first","affiliation":[{"name":"Renal Research, Gosford, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce S","family":"Spinowitz","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, New York-Presbyterian Queens, New York, NY, 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