New test may help patients with cystic fibrosis

Researchers have developed a simple urine test to measure the severity of the serious disease of cystic fibrosis and to assess the effect of new treatments.

A newly developed urine test may make it easier for doctors to diagnose how badly a patient is affected by the inherited disease of cystic fibrosis, which, among other things, affects the body’s respiratory, digestive and reproductive systems.

The test can also reveal how beneficial the patient’s medical treatment is. This is shown by a new study from Aarhus University and Aarhus University Hospital which has just been published in the scientific journal Annals of Internal Medicine.

Cystic fibrosis is caused by mutations in the CFTR gene which codes for the ion channel called CFTR. An important function of CFTR is to regulate the production of fluid and mucus in the lungs and digestive fluids in the intestine. Loss of CFTR function leads to thick mucus in the lungs and reduced amounts of digestive fluids. The consequence is inflammations and blockages that damage the organs. CFTR is also expressed in the kidneys where it alters electrolyte handling.

Now, focusing on the kidneys and urine, the researchers have come up with a simple test, which probably shows the effectiveness of the treatment for each patient.

“The goal is for the urine test to be used as a clinical tool to determine both the severity of genetic dysfunction and the reparative effect of the drug in individual patients with cystic fibrosis,” says Professor Jens Leipziger of the department of Biomedicine from Aarhus University, who is one of the main actors behind the study, together with Peder Berg, consultant Majbritt Jeppesen and consultant Søren Jensen-Fangel.

Better and easier than sweat testing

Among other functions, the kidneys regulate acid-base balance in the body, and studies have shown that patients with cystic fibrosis have a significantly reduced ability to increase basal excretion through the kidneys compared to healthy control subjects. This discovery led the researchers to test the ability of patients to increase the base content of urine, as a measure of CFTR function and therefore disease severity, as well as the degree of normalization after treatment.

Until now, measurement of chloride concentration in sweat was the most widely used method to assess a patient’s CFTR function. However, this method is time-consuming, requires experienced personnel, has large intra-individual variations, and does not adequately reflect disease severity. It is therefore an important finding that urinary bicarbonate excretion can be used to characterize CFTR function and hence disease severity.

In 2020, a new drug, Kaftrio®, was approved in Denmark. Today, most Danish patients with cystic fibrosis are treated with this drug, which improves the activity of the defective CFTR molecule.

The new drug is expected to significantly improve the health of patients. In this study, researchers examined 50 adult patients with the disease before and after treatment with Kaftrio®.

“The management of cystic fibrosis has changed with the recent introduction of treatments targeting the mechanism responsible for the disease. As new treatments aim to improve the functioning of the CFTR, the urine test can provide a measure of the effectiveness of a given treatment”, explains Jens Leipziger.

Another important finding is a clear correlation between the results of the urine test and the severity of the disease, such as the degree of reduced lung function.

More patients will have a better outcome

The new treatment is expected to significantly improve life expectancy and quality of life for patients with cystic fibrosis. The study conducted by Aarhus University and Aarhus University Hospital reveals that after six months of treatment with Kaftrio®, patients achieve on average about 70% of the baseline excretion rate observed in subjects healthy controls.

However, at present, all patients with cystic fibrosis are given the same dosage of the drug – although doctors are seeing differences in both the side effects and the clinical effects of the drug.

“We know that the drug is absorbed, metabolized and excreted differently from person to person. If, with a simple test, we can monitor the effects of the drug for each patient, we expect that patients can achieve a better treatment outcome,” says Jens Leipziger.

This requires the clinical use of the test, and is therefore particularly relevant in the long term. The current results represent an early step in the development of the urine test, which is why several clinical trials have been initiated to study its clinical applicability.

Behind the search results

• Prospective cohort study carried out within the framework of a collaboration between the Department of Biomedicine of the University of Aarhus and the Department of Infectious Diseases and the Department of Children and Adolescents of the AUH.
• The study is funded by the Innovation Fund of Denmark.
• Jens Leipziger and Peder Berg are the inventors of a patent application filed by AU, which describes the use of bicarbonate excretion as a biomarker in patients with cystic fibrosis.
• Read more in the scientific article: https://annals.org/aim/article/doi/10.7326/M22-1741

Contact

Professor Jens Leipziger
Aarhus University, Department of Biomedicine
Mobile: +45 6020 2760
Email: leip@biomed.au.dk