How altered bile acids may influence chronic kidney disease progression

Scientists find how changes in bile acids linked to gut bacteria may signal advancing chronic kidney disease, pointing to a possible link between gut metabolism and kidney decline

Alterations in bile acid metabolism resulting from changes in gut chemistry may play a significant role in the progression of chronic kidney disease (CKD), according to new research published in the journal Nephrology.

 

The study, titled A Comprehensive Analysis of Serum and Urine Bile Acid Profiles in Chronic Kidney Disease: An Exploratory Study of Clinical Associations, analysed bile acids, better known for helping digest fats, in the blood and urine of patients with advanced CKD and found significant changes in their composition despite similar overall levels. The study included 29 patients with advanced chronic kidney disease and 30 age- and sex-matched individuals with normal renal function.

 

 

Researchers observed higher levels of sulfate-conjugated bile acids in the blood and markedly reduced bile acid excretion in urine among patients with advanced CKD. Several specific bile acids were also independently associated with poorer kidney function, suggesting that disrupted bile acid processing may be closely linked to disease severity and progression.

What are bile acids, and why do they matter in kidney disease?

Bile acids are compounds made from cholesterol in the liver and modified by gut bacteria. They help digest and absorb fats, but they also act as signalling molecules that influence inflammation, metabolism, and gut health.

 

In recent years, scientists have become increasingly interested in the “gut–kidney axis”. People with CKD often have an altered gut microbiome, or dysbiosis, which can promote inflammation and the build-up of uremic toxins. Because bile acids sit at the intersection of liver function, gut bacteria, and metabolic signalling, researchers suspect they may offer important clues about what is happening beneath the surface in CKD.

What did the study find?

The researchers analysed both blood and urine samples of the participants using comprehensive bile acid profiling techniques, allowing the team to compare not just quantities but also the types of bile acids present.

 

They found that total serum bile acid concentrations were not significantly different between patients with advanced CKD and healthy controls.

 

At first glance, this might suggest that bile acids are not involved in kidney disease at all. But when the researchers looked beyond totals and examined bile acid composition, clear differences emerged.

 

Patients with advanced CKD had significantly lower levels of unconjugated bile acids in their blood. At the same time, they showed a marked increase in sulfate-conjugated bile acids compared with people with normal kidney function.

 

This shift suggests that while the overall amount of bile acids may remain stable, the way they are processed, modified, or cleared from the body changes as kidney disease progresses. Sulfate conjugation is a detoxification step, hinting that the body may be trying to compensate for impaired renal clearance.

 

According to the study, people with CKD had a dramatic reduction in total urinary bile acid excretion. Most bile acid subgroups were significantly lower in urine compared with controls.

 

This pattern is consistent with impaired kidney handling of bile acids. When the kidneys are damaged, their ability to filter and excrete these compounds declines, potentially contributing to their accumulation or altered processing in the bloodstream.

 

Several individual serum bile acids showed strong associations with declining kidney function, measured by estimated glomerular filtration rate (eGFR).

 

Higher levels of ursodeoxycholic acid, chenodeoxycholic acid, and sulfate-conjugated bile acids were independently associated with lower eGFR, even after accounting for factors such as age, sex, and diabetes. This strengthens the case that bile acid alterations may be linked to disease severity.

Does this mean bile acids cause CKD progression?

The study authors say this was an exploratory, cross-sectional study, which means it can identify associations but cannot prove cause and effect.

 

However, the findings strongly support the idea that disrupted bile acid metabolism accompanies advanced CKD and may interact with inflammation, gut dysbiosis, and metabolic pathways involved in disease progression. Whether bile acids actively worsen kidney damage or reflect broader metabolic stress remains an open and important question.

Why is this research important for the future of CKD care?

Although the study is limited by its small sample size, it gives a new perspective on CKD biology. By showing that bile acid composition and conjugation patterns change significantly in advanced disease, it opens the door to new lines of research.

 

In the future, bile acid profiling could help researchers better understand the gut–kidney connection, identify new biomarkers of disease progression, or even explore therapies aimed at modulating bile acid pathways or the gut microbiome.  For more health updates, follow #HealthWithBS