{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:59:33Z","timestamp":1789520373065,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T00:00:00Z","timestamp":1727049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012774","name":"Innovationsfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Renal excretion of excess HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> depends on renal cystic fibrosis transmembrane conductance regulator (CFTR) and is impaired in people with cystic fibrosis (pwCF). Urine HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> excretion following oral NaHCO<jats:sub>3<\/jats:sub>\u2010loading may be a simple in\u00a0vivo biomarker of CFTR function. In this study, we investigated changes in urine acid\/base parameters following oral NaHCO<jats:sub>3<\/jats:sub>\u2010loading to comprehensively assess the physiological response to the test and evaluate HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> as the primary test result.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Urine acid\/base parameters (titratable acid\u00a0(TA), NH<jats:sub>4<\/jats:sub><jats:sup>+<\/jats:sup>, net acid excretion (NAE) and pH) were measured in bio\u2010banked urine samples from controls (<jats:italic>n<\/jats:italic>\u2009=\u200910) and pwCF (<jats:italic>n<\/jats:italic>\u2009=\u200950) who completed the challenged urine HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> test. The association between urine acid\/base excretion parameters and clinical CF disease characteristics and CFTR modulator therapy\u2010induced changes were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Before treatment, challenged urine acid\/base excretion associated with important CF disease characteristics. TA excretion and NAE were lower in pwCF with residual function mutations, 7.9 and 16.6\u2009mmol\/3\u2009h, respectively, and lower TA excretion and NAE associated with pancreatic sufficiency. A lower excretion of TA, NH<jats:sub>4<\/jats:sub><jats:sup>+<\/jats:sup>, and NAE associated with a higher percentage of predicted FEV<jats:sub>1<\/jats:sub> (1.3%, 2.5% and 0.8% per mmol\/3\u2009h higher, respectively). Modulator treatment decreased TA excretion and NAE (\u22122.9 and \u22125.3\u2009mmol\/3\u2009h, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Following acute NaHCO<jats:sub>3<\/jats:sub>\u2010loading, increased base excretion is mirrored by decreased acid excretion. Urine HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> excretion sufficiently represents the additional urine acid\/base parameters as test result. The observed changes in acid excretion support CFTR modulator\u2010induced increase of CFTR\u2010dependent type B intercalated cell HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> secretion and the use of the challenged urine HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> test as a possible CFTR\u2010biomarker.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.14233","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T07:48:56Z","timestamp":1727077736000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The challenged urine bicarbonate excretion test in cystic fibrosis: A comprehensive analysis of urine acid\/base parameters"],"prefix":"10.1111","volume":"240","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8762-4733","authenticated-orcid":false,"given":"Amalie Q.","family":"Rousing","sequence":"first","affiliation":[{"name":"Department of Biomedicine Aarhus University  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