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Hepatorenal Syndrome

Hepatorenal Syndrome (HRS) is a life-threatening condition that affects kidney function in people with advanced liver disease. HRS is most common in people with advanced cirrhosis (or scarring of the liver) and ascites, an abnormal buildup of fluid in the abdomen that is often related to liver disease. But the syndrome can also occur in people with fulminant hepatic failure (acute liver failure) and other types of diseases of the liver.

There are two types of hepatorenal syndrome:

  • Type 1 (Acute) involves a rapid decline in kidney function and can quickly progress to life-threatening kidney failure. Your kidneys, which are part of your urinary tract, perform a number of vital functions, including filtering your blood to remove waste and extra fluid from your body. Signs of declining kidney function may include a significant reduction in urination; confusion; swelling caused by the buildup of fluid between tissues and organs (a condition known as edema) and abnormally high levels of nitrogen-rich, body-waste compounds in the blood (a condition known as azotemia).
  • Type II involves a more-gradual decrease in kidney function. Type II often leads to an abnormal buildup of fluid in the abdomen (ascites) that is resistant to treatment with diuretics. Sometimes referred to as water pills, diuretics can help rid your body of salt (sodium) and water and lower your blood pressure. People diagnosed with HRS Type II have a longer median survival time than those with Type I.

Although HRS can occur in people with advanced liver disease, its exact cause and rate of occurrence are still unknown.

The hallmark of the syndrome is significant narrowing (constriction) of the blood vessels that feed the kidneys. When blood flow to the kidneys is restricted, kidney function declines over time. The exact cause of constriction of the blood vessels feeding the kidneys remains unknown, but some researchers believe it may result from a combination of factors, including high pressure within the portal vein (portal hypertension), which carries blood from the digestive organs to the liver. The most-common cause of portal hypertension is cirrhosis of the liver.

There are various theories on the cause of HRS. The most common theory is that HRS is caused by a narrowing of the blood vessels that feed the kidneys, resulting in reduced blood flow to the kidneys and declining kidney function over time.

Researchers have also identified certain “triggers” that can make it more likely for people with liver disease to develop HRS. Spontaneous bacterial peritonitis (SBP) is the most common of these triggers. SBP is a complication of cirrhosis and ascites. It is an infection of the membrane lining the abdominal cavity. Another cause is too many diuretics (pills that promote urination).

If you have cirrhosis, the following will be important to prevent HRS:

  • Avoid nonsteroidal anti-inflammatory drugs (NSAIDs). These include aspirin, ibuprofen (Advil, Motrin, etc.), naproxen (e.g., Aleve), and many other generic and brand name drugs
  • Avoid contrast dyes used for certain medical tests such as MRIs and CT scans, and
  • Don’t drink  excessive amounts of alcohol

HRS has a variety of nonspecific symptoms, including:

  • Fatigue
  • Abdominal pain
  • A general feeling of illness (or malaise)

People with HRS may also have symptoms related to advanced liver disease, including:

  • A yellow tint to the skin or eyes caused by an excess of bilirubin in the blood (jaundice)
  • An abnormal buildup of fluid in the abdomen (ascites)
  • An enlarged spleen (splenomegaly)
  • A temporary worsening of brain function (confusion and/or memory loss) related to hepatic encephalopathy

There is no specific test for HRS. So, it is diagnosed in part by ruling out other causes of acute kidney impairment in patients with advanced liver disease.

Medical professionals conduct a thorough clinical evaluation; take a detailed patient history and order various tests. By doing so, they seek to determine whether certain conditions exist — including advanced liver failure with portal hypertension, and to rule out other causes of kidney impairment, such as:

  • Urinary or kidney disease
  • Bacterial infection
  • Shock (a sudden drop in blood flow through the body)
  • Recent treatment with certain drugs that affect kidney function, or so-called nephrotoxic drugs
  • Overuse of diuretics (also known as water pills)

One of the tests used to diagnose HRS is a common blood test known as a serum creatinine test. The test measures the level of creatinine in the blood, and the results reflect how well the kidneys are functioning. One of the signs of HRS is an abnormally high level of creatinine in the blood. Creatinine is a chemical waste product generated largely by the muscle-metabolism process.

The International Club of Ascites — an organization that encourages scientific research in the field of advanced liver cirrhosis and its complications — has developed its own criteria for the diagnosis of HRS.

Liver transplantation is the best treatment for HRS but may not be an option for people with HRS-1 who are too sick for the operation.  People who are either ineligible for a transplant or waiting for one may be given renal replacement therapy (hemodialysis) or medications to improve the flow of blood to the kidneys.

Those affected by HRS may also be advised by their medical team to avoid diuretics (which can worsen kidney function), promptly treat infection, and maintain their electrolyte balance. The major electrolytes in the body include sodium, potassium, calcium, magnesium, phosphate and chloride. Medical providers can determine electrolyte levels with a few tests and recommend how to best address an imbalance.

In some cases, people affected by HRS — particularly those needing dialysis or suffering from advanced kidney failure in the months leading up to a planned liver transplant — may need a kidney transplant as well as a  liver transplant.

Even after a successful liver transplant, kidney problems may persist, sometimes requiring dialysis. Dialysis is a treatment that removes waste, salt and extra water from the body and replicates other functions normally done by healthy kidneys.

Potential new treatments are being studied.  You can learn about privately and publicly funded clinical studies of treatments for HRS and other conditions at the National Institutes of Health’s clinical trials finder or by clicking here.

Other options for people who are unable to get a transplant or who are awaiting one include:

  • Vasoconstrictive agents to increase blood pressure that is too low
  • Albumin to improve renal function

The prognosis for people with liver failure is much worse if they develop HRS. Most patients die within weeks of the onset of renal (kidney) failure without therapy. In fact, 50% of people die within 2 weeks of diagnosis and 80% of people die within 3 months of diagnosis.

Early detection is critical. People affected by HRS have a higher chance of survival if the condition is diagnosed early; they receive prompt medical treatment for kidney impairment and liver transplant is feasible and available. A liver transplant improves the survival rate for individuals with either type of HRS.


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