Challenged Urine Bicarbonate Excretion as a Measure of Cystic Fibrosis Transmembrane Conductance Regulator Function in Cystic Fibrosis.
Ann Intern Med
; 175(11): 1543-1551, 2022 11.
Article
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| ID: mdl-36315944
ABSTRACT
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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Regulador de Conductancia de Transmembrana de Fibrosis Quística
/
Fibrosis Quística
Tipo de estudio:
Clinical_trials
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Etiology_studies
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Observational_studies
Idioma:
En
Revista:
Ann Intern Med
Año:
2022
Tipo del documento:
Article