Study design (if review, criteria of inclusion for studies)
Prospective observational study.
Participants
50 adult patients with CF starting CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor between May 2020 and June 2021. Cystic fibrosis clinic, Aarhus University Hospital, Denmark.
Interventions
elexacaftor/tezacaftor/ivacaftor
Outcome measures
Quantification of urine bicarbonate excretion after an acute oral sodium bicarbonate challenge before and 6 months after elexacaftor/tezacaftor/ivacaftor treatment.
Main 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%.
Authors' conclusions
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.