A new study has found an association between challenged urine bicarbonate excretion and clinical characteristics in cystic fibrosis (CF).

The study, published in the Annals of Internal Medicine, observed partially restored renal cystic fibrosis transmembrane conductance regulator (CFTR) function in patients with CF undergoing therapy with elexacaftor/tezacaftor/ivacaftor.

“The objective of this study was to conduct an initial assessment of a novel, noninvasive in vivo method to quantify CFTR function in humans,” the authors wrote. “We developed a standardized oral sodium bicarbonate challenge test on the basis of the inability of patients with CF to increase renal base excretion after oral sodium bicarbonate loading.”

The research team conducted an exploratory, prospective observational study on 50 adult patients with CF and 10 healthy controls at a single center in Denmark. They applied their oral sodium bicarbonate challenge test before and after elexacaftor/tezacaftor/ivacaftor therapy with the aim of correlating treatment-induced changes in bicarbonate excretion with CF characteristics and variation in test results in the control participants.

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The results revealed that urine bicarbonate excretion was higher in participants with residual function mutations, as well as in those with better lung function and pancreatic sufficiency. Furthermore, bicarbonate excretion was higher in those at lower risk of chronic Pseudomonas aeruginosa infection.

Treatment with elexacaftor/tezacaftor/ivacaftor increased bicarbonate excretion to about 70% of that of the control participants and likely reduced the risk of electrolyte disorders and metabolic alkalosis in the patients with CF.

Although further studies to assess the sensitivity and performance of urine bicarbonate excretion as a biomarker are warranted, these early results suggest the approach could be a simple and noninvasive way to quantify CFTR function. This method also offers the ability to assess the extent of restoration of renal function post-therapy with elexacaftor/tezacaftor/ivacaftor.

Reference

Berg P, Sorensen M, Quist Rousing A, et al. Challenged urine bicarbonate excretion as a measure of cystic fibrosis transmembrane conductance regulator function in cystic fibrosis. Ann Internal Med. Published online November 1, 2022. doi:10.7326/M22-1741