Challenged Urine Bicarbonate Excretion as a Measure of Cystic Fibrosis Transmembrane Conductance Regulator Function in Cystic Fibrosis
| Autor: | Peder Berg, Mads V. Sorensen, Amalie Quist Rousing, Hanne Vebert Olesen, Søren Jensen-Fangel, Majbritt Jeppesen, Jens Leipziger |
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| Rok vydání: | 2022 |
| Předmět: |
Adult
Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator General Medicine Bicarbonates Drug Combinations Chloride Channel Agonists/pharmacology Mutation Internal Medicine Cystic Fibrosis Transmembrane Conductance Regulator/genetics Humans Bicarbonates/metabolism Cystic Fibrosis/drug therapy Chloride Channel Agonists |
| Zdroj: | Berg, P, Sorensen, M V, Rousing, A Q, Olesen, H V, Jensen-Fangel, S, Jeppesen, M & Leipziger, J 2022, ' Challenged Urine Bicarbonate Excretion as a Measure of Cystic Fibrosis Transmembrane Conductance Regulator Function in Cystic Fibrosis ', Annals of Internal Medicine, vol. 175, no. 11, pp. 1543-1551 . https://doi.org/10.7326/M22-1741 |
| ISSN: | 1539-3704 0003-4819 |
| DOI: | 10.7326/m22-1741 |
| Popis: | BACKGROUND: In cystic fibrosis (CF), renal base excretion is impaired. Accordingly, challenged urine bicarbonate excretion may be an in vivo biomarker of cystic fibrosis transmembrane conductance regulator (CFTR) function.OBJECTIVE: To evaluate the association between challenged bicarbonate excretion and clinical characteristics at baseline, quantify the CFTR modulator drug elexacaftor/tezacaftor/ivacaftor-induced changes of challenged bicarbonate excretion after 6 months of treatment, and characterize the intraindividual variation in healthy adults.DESIGN: Prospective observational study.SETTING: Cystic fibrosis clinic, Aarhus University Hospital, Denmark.PATIENTS: Fifty adult patients with CF starting CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor between May 2020 and June 2021.MEASUREMENTS: Quantification of urine bicarbonate excretion after an acute oral sodium bicarbonate challenge before and 6 months after elexacaftor/tezacaftor/ivacaftor treatment.RESULTS: At baseline, challenged urine bicarbonate excretion was associated with several CF disease characteristics. Bicarbonate excretion was higher in patients with residual function mutations. A higher bicarbonate excretion was associated with better lung function, pancreatic sufficiency, and lower relative risk for chronic pseudomonas infections. Elexacaftor/tezacaftor/ivacaftor treatment increased bicarbonate excretion by 3.9 mmol/3 h (95% CI, 1.6 to 6.1 mmol/3 h), reaching about 70% of that seen in healthy control participants. In healthy control participants, individual bicarbonate excretion at each visit correlated with the individual mean bicarbonate excretion. The median coefficient of variation was 31%.LIMITATION: Single-center study without a placebo-controlled group.CONCLUSION: Although further studies are needed to address the performance and sensitivity of this approach, this early-stage evaluation shows that challenged urine bicarbonate excretion may offer a new, simple, and safe quantification of CFTR function and the extent of its pharmacologic improvement. Elexacaftor/tezacaftor/ivacaftor partially restores renal CFTR function in patients with CF, likely resulting in decreased risk for electrolyte disorders and metabolic alkalosis.PRIMARY FUNDING SOURCE: Innovation Fund Denmark. |
| Databáze: | OpenAIRE |
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