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Urine Bicarbonate Test Offers Safe Quantification of CFTR Function in Cystic Fibrosis Patients

By LabMedica International staff writers
Posted on 02 Nov 2022
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Image: Challenged urine bicarbonate excretion offers safe assessment of reduced CFTR function (Photo courtesy of Pexels)
Image: Challenged urine bicarbonate excretion offers safe assessment of reduced CFTR function (Photo courtesy of Pexels)

The management of cystic fibrosis has changed with the recent introduction of therapies that target the disease-causing mechanism. Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, including elexacaftor, tezacaftor, and ivacaftor, are novel drugs that either potentiate or correct CFTR channel dysfunction. They can partially restore CFTR function. Measurement of sweat chloride concentration is the most used method to assess CFTR function in vivo. However, sweat chloride only associates marginally with clinical disease features, is time consuming, requires experienced staff, and has large intraindividual variation. Many other biomarkers for CFTR exist but have complicated approaches that limit their clinical use. Now, a study of patients with cystic fibrosis has found that challenged urine bicarbonate excretion may offer a new, simple, and safe quantification of CFTR function and the extent of its pharmacologic improvement.

Renal dysfunction may be related to cystic fibrosis and may be measured through tests quantifying bicarbonate secretion in the kidney that occurs via pendrin, according to a study by researchers from Aarhus University (Aarhus, Denmark). CFTR is fully necessary for the function and regulation of pendrin, which in cystic fibrosis leads to an impaired ability to excrete excess bicarbonate. These patients have a reduced ability to increase renal base excretion after oral sodium bicarbonate loading, making a challenge test a potential option for drug treatment monitoring.

For the study, the researchers studied 50 adult patients with cystic fibrosis starting CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor to evaluate the association between challenged bicarbonate excretion and clinical characteristics at baseline, quantify the CFTR modulator drug–induced changes of challenged bicarbonate excretion after six months of treatment, and characterize the intraindividual variation in healthy adults. The researchers evaluated and quantified urine bicarbonate excretion after an acute oral sodium bicarbonate challenge before and six months after elexacaftor/tezacaftor/ivacaftor treatment.

The researchers found that challenged urine bicarbonate excretion was associated with cystic fibrosis disease characteristics. The use of elexacaftor/tezacaftor/ivacaftor increased bicarbonate excretion to about 70% of that seen in control participants. According to the researchers, their early-stage evaluation shows that that challenged urine bicarbonate excretion offers a new, simple, and safe functional assessment quantifying the biological consequences of reduced CFTR function and the extent of functional recovery after pharmacologic treatment.

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Aarhus University 

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