Hepatorenal Syndrome (HRS)

What is hepatorenal syndrome (HRS)?

Hepatorenal syndrome (HRS) is a life-threatening complication of advanced liver disease that affects your kidney function. It causes prerenal acute kidney failure. That means that it comes on suddenly, without any previous kidney disease or any physical changes to the kidneys themselves. Your kidneys may be healthy, but they lose the ability to function because their blood supply has been compromised.

People with hepatorenal syndrome have narrowed and constricted blood vessels in their kidneys in response to liver failure, which reduces blood flow to the kidneys. This progressively slows down kidney functions. Hepatorenal syndrome requires urgent intervention, and in most cases, a liver transplant is the only cure.

Who does hepatorenal syndrome affect?

Hepatorenal syndrome affects people with severe liver disease. It usually occurs in people who have had chronic, progressive liver disease for some time and who are on the threshold of liver failure. Chronic liver disease results in cirrhosis, scarring of the liver tissues, which changes its blood supply and stops it from functioning over time. HRS can also occur with acute liver failure resulting from some sudden cause.

Studies suggest that up to 40% of people with end-stage liver disease will develop HRS. These people represent all ages and sexes. They are more often in the second half of their lives. Up to 10% of people hospitalized with chronic or acute liver failure will develop it. Although liver disease can cause kidney failure in more than one way, HRS develops in people with no prior evidence of kidney disease.

How does cirrhosis cause hepatorenal syndrome?

Pathophysiology

The exact pathophysiology of hepatorenal syndrome — how it develops as a result of liver disease — is still in debate. We do know that narrowed and constricted blood vessels in the kidneys reduce their blood supply, causing dysfunction. Researchers believe this narrowing may be caused by a combination of factors related to liver disease and liver failure. The most common factor is portal hypertension.

Portal hypertension is high blood pressure in the portal vein that runs through your liver. It causes the vein and its branches throughout your digestive system to widen. Cirrhosis is its most common cause. Cirrhosis can also cause cirrhotic cardiomyopathy, which causes abnormal widening of certain arteries in your body. Complex blood flow dynamics cause some vessels to narrow when others widen.

Precipitating Factors

Other factors associated with liver disease may be possible “triggers” that make HRS more likely to onset. The most common one is spontaneous bacterial peritonitis (SBP), an infection of the peritoneum, the tissues that line your abdomen. SBP is a complication of ascites, which is the accumulation of fluid in your peritoneum. Ascites is a side effect of portal hypertension, which causes your abdominal veins to leak.

Portal hypertension can also cause your veins to break and bleed into your abdominal cavity. Acute blood loss from gastrointestinal bleeding is another possible trigger. So is the overuse of diuretics (“water pills”). Diuretics help clear out accumulated fluid from your body. People with advanced liver disease may take diuretics for symptoms such as ascites or edema, swelling caused by fluid retention.

What are the symptoms of hepatorenal syndrome?

People with hepatorenal syndrome tend to have vague symptoms of general unwellness, such as:

• Fatigue.
• Nausea.
• Stomach ache.
• Bad taste in the mouth.

They may also have symptoms of advanced liver disease or liver failure, such as:

• Jaundice (yellowing of the whites of the eyes).
• Easy bruising and bleeding.
• Light-colored poop and dark-colored pee.
• Swollen abdomen (due to ascites, enlarged liver or enlarged spleen).
• Itchy skin.
• Confusion, disorientation or drowsiness (hepatic encephalopathy).

When kidney failure becomes severe, you will notice low urine output.

How is hepatorenal syndrome diagnosed?

Hepatorenal syndrome is kidney failure that occurs with advanced liver disease and in the absence of other causes of kidney failure. So, healthcare providers diagnose it by first confirming liver disease and kidney failure, and then ruling out other possible causes of kidney failure. They will use a variety of imagining tests, blood tests and urine tests to evaluate your liver function and kidney function.

How is hepatorenal syndrome treated?

Kidney failure makes HRS urgent, but liver disease is the root of the problem. Hepatorenal syndrome is classified as “prerenal” acute kidney failure because it happens when your kidneys are otherwise healthy. In fact, if your kidneys were transplanted into someone else’s body, they would work just fine. By the same token, your kidneys are likely to regain their functionality if you regain liver functionality.

Some people with acute liver failure may recover their liver and kidney functionality. All others will need a liver transplant. They may have needed a transplant eventually, but HRS makes the need more urgent. However, not everyone qualifies for a liver transplant, and those who do may have to wait to get one.

In the meantime, your healthcare provider will work to preserve your kidney function as much as possible and alleviate symptoms and side effects of the condition. These steps may help to improve your overall condition and make you more fit for liver transplant surgery. They may also improve your outcome if you do have liver transplant surgery. But they aren’t curative. Therapies may include:

• IV fluids to treat electrolyte imbalances and support blood flow to your kidneys.
• Discontinuing certain medications, such as diuretics.
• Antibiotics to treat any related infections.
• Paracentesis to remove excess fluid from ascites.
• Vasoconstrictors, medicines that reduce your abnormally widened blood vessels and increase blood flow to your kidneys.
• Hemodialysis to support your stressed kidneys.

Can hepatorenal syndrome be prevented?

The best way to prevent hepatorenal syndrome is to manage liver disease before it progresses to cirrhosis. Chronic liver disease progresses slowly over many years. Those who are aware of it can often slow or reverse it by taking steps such as quitting alcohol use, losing weight and improving their diet. However, many people don’t have symptoms, and may not discover it without a routine checkup.

If you already have cirrhosis, there’s no way to predict or prevent the onset of HRS. But you may be able to prevent spontaneous bacterial peritonitis (SBP), which is the most common “trigger.” SBP in people with cirrhosis precipitates up to 25% of HRS cases. Taking antibiotics preventatively if your provider believes you are at particularly high risk for SBP can reduce the possibility of developing HRS by reducing this precipitating factor.

Can you survive hepatorenal syndrome?

Without a liver transplant, the outlook for most people is grim. The median survival rate for people with acute onset HRS and no transplant is two weeks. With more chronic HRS, the median survival rate without a transplant is three to six months. Those with more advanced liver failure will decline more rapidly. Rapid decline could also complicate your condition by making you too sick to safely undergo transplant surgery.

However, if you do have a liver transplant, your outlook is much better. The survival rate after liver transplant for people with HRS is 60% when measured three years later. This is only slightly lower than the three-year survival rate for liver transplant recipients in general (75%). Most people will also regain their kidney functionality over the following weeks. A small number (5%) may require ongoing dialysis.

A note from Cleveland Clinic

Whether you are in the slow decline of end-stage liver disease, or whether the onset of hepatorenal syndrome suddenly speeds up your timeline, the liver donor waiting list is not an enviable list to be on. There are far more people on the list than there will be donor livers available. But you can skip the list and improve your overall health outcomes if you are able to find a living liver donor.

Living donors are healthy volunteers, usually loved ones, with a compatible blood type and body size to yours. Just a piece of a liver from another living person can grow back into a full-sized liver in both you and your donor. Living livers also tend to be in better condition than deceased donor livers. Surgeons make every effort to make transplant surgery minimally invasive for their heroic living donors.