Ursodeoxycholic Acid: Effects on the Liver and Kidneys

Ursodeoxycholic acid, usually shortened to UDCA or ursodiol, is a bile acid medicine prescribed in the UK for specific liver and gallbladder conditions. It also attracts interest from people seeking general 'liver protection'. Our editorial team explains how UDCA works, what it can and cannot do for the liver, and what is known about its effects on the kidneys.

What UDCA is

UDCA is a naturally occurring hydrophilic bile acid. In human bile it makes up only a small proportion of the total bile acid pool, but when taken as a medicine it becomes a dominant component, changing the overall character of bile from more toxic, detergent-like acids to gentler ones.

In the UK, UDCA is a prescription-only medicine. Licensed indications include primary biliary cholangitis (PBC) and dissolution of small cholesterol gallstones in a functioning gallbladder. Specialists also use it in some other cholestatic conditions, including intrahepatic cholestasis of pregnancy and certain paediatric liver diseases.

For PBC, product information and guidelines describe a dose of around 13–15 mg per kilogram of body weight per day. This is stated here as a fact of official labelling; the appropriate dose for any individual is decided by their specialist.

UDCA is generally well tolerated, which partly explains its popularity beyond licensed uses. However, a good safety profile in supervised patients is not the same as proven benefit in healthy people who take it on their own initiative.

How UDCA acts in the liver

UDCA works through several mechanisms. It displaces more toxic hydrophobic bile acids, reducing their damaging effect on liver cells and bile duct cells. It also stimulates bile secretion by liver cells, improving bile flow in cholestatic conditions.

At a cellular level, UDCA appears to protect liver cells from bile acid-induced apoptosis, a form of programmed cell death, and to stabilise cell membranes. It may also support a protective bicarbonate layer along the bile ducts, sometimes called the bicarbonate umbrella.

In PBC, these effects translate into improved liver blood tests, and long-term studies show better transplant-free survival in patients who respond to treatment. UDCA is therefore the first-line therapy recommended by EASL and UK guidelines for this disease.

In contrast, a large trial in primary sclerosing cholangitis found that high-dose UDCA was associated with worse outcomes than placebo. This shows that UDCA's effects are condition-specific and dose-dependent rather than universally protective.

Evidence beyond licensed indications

Researchers have tested UDCA in non-alcoholic fatty liver disease, now often called MASLD. Overall, standard-dose trials have not shown convincing improvements in liver histology, and UDCA is not recommended as a treatment for this condition in current guidelines.

In drug-induced liver injury, UDCA is sometimes used empirically for cholestatic patterns, but evidence from controlled trials is limited. The cornerstone of management remains stopping the offending drug and monitoring.

Among gym users, UDCA is sometimes taken alongside oral anabolic steroids in the belief that it prevents liver damage. There are no controlled studies demonstrating this, and the practice may give false reassurance while serious liver injury progresses.

Effects on the kidneys

The kidneys and liver are closely linked in bile acid handling. When bile flow is blocked, bile acids accumulate in blood and are increasingly excreted in urine. Very high bilirubin and bile acid levels can damage renal tubules, a condition known as cholemic nephropathy or bile cast nephropathy.

Animal research, including work by Fickert and colleagues, suggests that hydrophilic bile acids such as norUDCA may protect the kidneys in cholestatic models. In patients, UDCA is sometimes used in severe cholestasis, but evidence that it prevents kidney injury in humans is limited.

UDCA itself is mainly handled by the liver and intestines rather than the kidneys, and it is not known to be nephrotoxic at standard doses. Kidney-related side effects are rarely reported in clinical use.

• UDCA is not regarded as harmful to healthy kidneys at licensed doses.
• It is not a proven treatment for kidney disease.
• Bile cast nephropathy requires treatment of the underlying cholestasis.
• People with kidney disease should still tell their doctor about any medicines they take.

Side effects, interactions and contraindications

The most common side effect is loose stools or diarrhoea. Rarely, patients report abdominal pain, itching or, in advanced PBC, a worsening of the disease. Gallstones can occasionally calcify during treatment.

UDCA should not be used in acute inflammation of the gallbladder or bile ducts, complete obstruction of the biliary tract, frequent biliary colic, or with calcified gallstones and a non-functioning gallbladder, according to product information.

Bile acid sequestrants and aluminium-containing antacids can bind UDCA and reduce its absorption. UDCA can affect ciclosporin levels, and oestrogens or some lipid-lowering drugs may counteract gallstone dissolution.

Because UDCA is prescription-only in the UK, buying it from unregulated online sources carries additional risks of counterfeit or contaminated products. The MHRA regularly warns about medicines purchased outside legitimate pharmacies.

Editorial conclusions

UDCA is an effective, well-tolerated medicine for specific conditions such as primary biliary cholangitis and selected gallstones.

It is not a general liver tonic: evidence for fatty liver is weak, and it does not make hepatotoxic substances safe.

At licensed doses it is not considered harmful to the kidneys, but it is not a treatment for kidney disease, and any use should be supervised by a doctor.

Our editorial team suggests reading next about TUDCA contraindications, liver function tests explained and drug-induced liver injury.

References

1. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017;67(1):145–172.
2. Lindor KD, Kowdley KV, Luketic VA, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009;50(3):808–814.
3. Beuers U, Trauner M, Jansen P, Poupon R. New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond. J Hepatol. 2015;62(1 Suppl):S25–S37.
4. Fickert P, Krones E, Pollheimer MJ, et al. Bile acids trigger cholemic nephropathy in common bile-duct-ligated mice. Hepatology. 2013;58(6):2056–2069.
5. Lindor KD, Kowdley KV, Heathcote EJ, et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology. 2004;39(3):770–778.
6. Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568–1594.
7. Chappell LC, Bell JL, Smith A, et al. Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES). Lancet. 2019;394(10201):849–860.