What are other Names for this Condition? (Also known as/Synonyms)

• HRS (Hepatorenal Syndrome)

What is Hepatorenal Syndrome? (Definition/Background Information)

• Hepatorenal Syndrome (HRS) is a serious complication of liver disease that adversely affects the functioning of the kidneys. It is a medical emergency requiring immediate treatment
• There are two types of Hepatorenal Syndrome:
  • Type 1 Hepatorenal Syndrome involves quickly progressive renal (kidney) failure; individuals with this type usually experience an extremely shortened lifespan after diagnosis. They are not typically known to live long enough to receive a liver transplant
  • Type 2 Hepatorenal Syndrome affected individuals experience a much slower kidney function deterioration and are known to survive long enough to receive a liver transplant
• The exact cause of Hepatorenal Syndrome is presently unknown but there are common factors associated with its development, including liver cirrhosis and disruptions of normal blood flow to the liver and kidneys
• The signs and symptoms of Hepatorenal Syndrome vary from one individual to another based on the specific state of liver infection and other preexisting health issues. It also depends on the subtype of HRS
• A diagnosis of Hepatorenal Syndrome includes a number of specialized tests to determine the reason for acute kidney failure. However, if kidney failure is observed in a patient with severe liver disease it is likely due to Hepatorenal Syndrome
• Hepatorenal Syndrome usually results in the eventual imminent failure of other organs as well as complications associated with the initial liver disease. Therefore, the prognosis for individuals with Hepatorenal Syndrome is typically poor unless a liver transplant is available in a timely manner
• Since the risk factors for Hepatorenal Syndrome are related to liver damage, and therefore preventing the syndrome involves treating liver disease early on, rather than managing the complications of the liver disease that lead to development of the syndrome

Who gets Hepatorenal Syndrome? (Age and Sex Distribution)

• Hepatorenal Syndrome affects about 10% of individuals with severe liver disease worldwide 
• It affects both males and females in about equal numbers
• Worldwide, individuals of all races, ethnicities, and geographic locations may be affected

What are the Risk Factors for Hepatorenal Syndrome? (Predisposing Factors)

The risk factors for Hepatorenal Syndrome may include:

• Blood pressure that falls when an individual stands up or suddenly changes his/her position, a condition termed orthostatic hypotension
• Gastrointestinal bleeding
• Use of diuretics (water pills)
• Recent abdominal fluid tap 
• Certain infections

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Hepatorenal Syndrome? (Etiology)

The exact cause of Hepatorenal Syndrome (HRS) is not well understood, but it occurs in individuals with late stage liver disease. Other factors associated with Hepatorenal Syndrome include:

• Individuals with scarring or dysfunction of the liver, called cirrhosis 
• Renal vasoconstriction - narrowing of the blood vessels that feed the kidney: The cause of this is unknown, but a few factors are believed to contribute, such as high blood pressure of the main blood vessel of the liver, physical abnormalities that disrupt normal blood flow, activation of factors that cause the blood vessels to narrow, and deactivation of factors that allow the blood vessels to widen
• In some individuals with Hepatorenal Syndrome, a few factors have been identified that act as triggers for individuals with liver disease in developing HRS. These include an infection of the thin membrane that lines the abdomen (a known complication in individuals with cirrhosis and the accumulation of fluid in the peritoneal cavity which causes abdominal swelling)

What are the Signs and Symptoms of Hepatorenal Syndrome?

Individuals with Hepatorenal Syndrome (HRS) may present a variety of signs and symptoms that can vary from one individual to another. The common signs and symptoms observed are:

• Fatigue
• Abdominal pain
• Malaise, an overall feeling of bad health
• Mental confusion
• Dark colored urine

Signs and symptoms related to severe liver disease that are observed include:

• Accumulation of fluid in the abdomen
• Yellowing of the skin and whites of the eyes (jaundice)
• Enlargement of the spleen
• Enlarged and tender liver

The signs and symptoms of Hepatorenal Syndrome also differ based on whether an individual has type 1 or type 2 HRS.

Type 1 Hepatorenal Syndrome: Individuals with this type have a condition that results from the inability of the liver to breakdown certain substances called hepatic encephalopathy. This results in mental health associated sign and symptoms such as:

• Confusion
• Drowsiness
• Noticeable changes in judgement and other intellectual processes

Type 2 Hepatorenal Syndrome: It causes kidney failure that occurs much slower than type 1 and does not usually result in hepatic encephalopathy as with type 1. Individuals with type 2 Hepatorenal Syndrome usually experience an accumulation of fluid in the abdomen that cannot be normally removed by diuretics.

How is Hepatorenal Syndrome Diagnosed?

A diagnosis for Hepatorenal Syndrome (HRS) is made following a physical examination and a careful examination of an individual’s medical history. The condition is typically diagnosed after ruling out other potential causes of kidney failure. In order to make an accurate diagnosis, certain criteria have been created that need to be met to make a diagnosis for HRS. 

Specialized tests need to be carried out and the following conclusions are often necessary to diagnose the condition:

• Advanced liver failure with portal hypertension
• High levels of creatinine
• Absence of other causes of kidney failure such as bacterial infection
• No improvement of kidney function with the removal of diuretics and expansion of plasma with albumin (a protein made in liver which is low in cases of liver disease)
• Low levels of protein in the urine with no evidence of urinary disease or parenchymal kidney disease

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Hepatorenal Syndrome?

The possible complications that can result from Hepatorenal Syndrome include:

• Secondary infections
• Bleeding 
• Damage or failure of several organs
• End-stage kidney disease
• Fluid excess with congestive heart failure or pulmonary edema 
• Hepatic coma

How is Hepatorenal Syndrome Treated?

The only way to successfully treat Hepatorenal Syndrome is by performing a liver transplant. Liver transplants are often difficult because the wait times for a liver can often be long. Also, individuals with type 1 Hepatorenal Syndrome tend to need a transplant immediately; the survival rate is low if the wait times are long.

Other treatments to help improve liver function and blood flow include:

• Stopping certain medications, such as ibuprofen and other nonsteroidal anti-inflammatory drug (NSAIDs), as well as certain antibiotics and diuretics, following appropriate consultation with the healthcare provider
• Urinary dialysis
• Taking medications that improve blood pressure and kidney function such as octreotide, albumin, dopamine, and norepinephrine
• Implanting a non-surgical shunt 
• Surgery to remove excess fluid from the abdomen (such as paracentesis)
• Surgical implantation of a shunt from the abdomen to the jugular vein to relieve some symptoms of kidney failure

Some symptoms of Hepatorenal Syndrome can be treated for a certain period of time, but without a liver transplant, the condition is often fatal.

How can Hepatorenal Syndrome be Prevented?

Prevention of Hepatorenal Syndrome is often difficult as it occurs because of preexisting liver damage. Therefore, preventative measures need to be taken to avoid liver disease which can include:

• Limiting alcohol use or drinking in moderation
• Avoiding use of drugs and maintain cleanliness with needles and materials used for body piercings and tattoos
• Getting any necessary or recommended vaccines
• Using medications wisely as directed by a medical professional
• Avoiding contact with blood and bodily fluids of other individuals
• Protecting skin when using pesticides or toxic chemicals
• Maintaining a healthy weight

Once liver disease has become apparent, there are fewer measures that can be taken to avoid Hepatorenal Syndrome, and these may include:

• Administering albumin to individuals who have spontaneous bacterial infections of the abdominal wall
• In individuals with liver damage due to alcohol consumption, treatment with pentoxifylline can improve blood flow and decrease the risk of Hepatorenal Syndrome
• Avoiding the use of diuretics if no benefit is being observed from their use 
• Use of medications to treat low blood pressure can be helpful in some patients. But depending on the state of the liver, certain medications can be detrimental if the liver cannot function well enough to break them down

What is the Prognosis for Hepatorenal Syndrome? (Outcomes/Resolutions)

• The prognosis of Hepatorenal Syndrome (HRS) is often poor, and deaths typically occur before a liver transplant is generally available
• Most cases of Hepatorenal Syndrome occur when liver disease is in a very late/advanced stage. Thus, in many, by the time there is onset of HRS, and a liver transplant is ordered (and is available), individuals do not have enough time and health to cope with the condition/transplant procedure
• The prognosis for type 1 Hepatorenal Syndrome is poorer than that of type 2 Hepatorenal syndrome in most cases. This is because deterioration of the liver occurs much faster in individuals with type 1 HRS than with type 2 disease

Additional and Relevant Useful Information for Hepatorenal Syndrome:

• In cases of individuals who have died due to complications of Hepatorenal Syndrome and liver disease, no histological differences are observed in the kidneys. This supports the evidence that is observed when an individual with Hepatorenal Syndrome receives a liver transplant
• When individuals receive a liver transplant, symptoms of kidney failure typically diminish, and kidney function is able to return to normalcy in some cases