Bicarbonate excretion in urine may serve as a CF marker: Study
Balance of acids and bases reflects lung, pancreas function in cystic fibrosis
The balance of acids and bases in the urine of people with cystic fibrosis (CF) reflects lung and pancreas function, and the response to treatment, a study finds.
The findings support measuring the bicarbonate base in urine, which mirrors the levels of various acids, as a tool to clinically assess CF status.
“Urine [bicarbonate] excretion sufficiently represents all urine acid/base excretions as test readout,” the researchers wrote. The study, “The challenged urine bicarbonate excretion test in cystic fibrosis: A comprehensive analysis of urine acid/base parameters,” was published in Acta Physiologica.
In CF, mutations impair the production or function of CFTR, a protein that controls the flow of water and salt molecules into and out of cells. Without CFTR, the mucus that coats the surfaces of tissues and organs becomes thick and sticky, triggering most CF symptoms.
CFTR is also found in the kidneys, which control the volume of various body fluids, the body’s acid-base balance, various salt concentrations, and the removal of waste products from the blood. CFTR dysfunction can reduce the kidneys’ ability to excrete bicarbonate, which normally helps regulate the acid-base balance. Sodium bicarbonate is better known as baking soda.
In 2022, scientists in Denmark sought to determine if urinary bicarbonate levels may be a useful CF assessment alternative to the sweat chloride test, which takes longer and requires trained specialists. Data showed a urinary bicarbonate test, taken after CF patients consumed a standardized dose of sodium bicarbonate, helped assess the effectiveness of CF treatments.
Measuring bicarbonate in CF
Here, the researchers used the samples collected in that study to investigate specific changes in the acid-base balance and assessed whether these changes were associated with clinical CF characteristics and treatment response.
The previous study measured bicarbonate in urine from 50 CF patients before and after six months of treatment with Kaftrio (elexacaftor/tezacaftor/ivacaftor), a CFTR modulator therapy that boosts CFTR’s function in people with at least one F508del mutation, the most common CF-causing mutation. Kaftrio is sold as Trikafta in the U.S. Urine samples from 10 healthy people were also tested.
The new study measured several urine acid-base parameters, including bicarbonate, ammonia (NH4+), titratable acid (TA), the amount of molecules such as phosphates or citrate needed to bring the urine pH back to 7.4, net acid excretion (NAE), which is the net amount of TA and ammonia minus bicarbonate, and pH. The average normal pH of the human body is 7.4.
Before treatment, excretion of TA and NAE was significantly lower, and bicarbonate was significantly higher in the healthy controls and CF patients with one F508del mutation than those with two F508del mutations. No differences were found for ammonia excretion.
A lower excretion of TA, ammonia, and NAE, and a higher excretion of bicarbonate were significantly associated with better lung function. Similar associations were found with pancreas function, though the link with ammonia wasn’t significant here. After adjustments, bicarbonate excretion alone was linked with a lower risk of persistent lung infections by Pseudomonas aeruginosa.
In other tests, higher bicarbonate excretion was associated with lower sweat chloride. Although lower TA and NAE also correlated with low sweat chloride, the association was mainly driven by control values, with no differences between the different CF groups, the researchers said. No relationship was found between ammonia excretion and sweat chloride.
Consistent with these findings, a higher mean urine pH, or less acid, correlated with better lung function and lower sweat chloride.
After six months on Kaftrio, TA and NAE significantly decreased, while bicarbonate increased. Ammonia levels weren’t affected by treatment.
“The relative simplicity of measuring challenged [bicarbonate] in urine and the confirmation of the [kidney] acid/base physiology indicates a possible user-friendly and reasonable approach to assess CFTR function,” the researchers wrote.
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