What Is Hepatorenal Syndrome?

Overview

Hepatorenal syndrome is a condition involving both your liver (hepatic) and kidneys (renal). By a mechanism that is not fully understood, hepatorenal syndrome causes your kidneys to stop working properly. The hallmark of disease is that, despite the absence of a defect in your kidneys, there is an obvious loss of function.¹ 

Hepatorenal syndrome can either be explosive, causing a rapid decline in your kidney function (type 1), or it may be more gradual, leading to the progressive damage of your kidneys (type 2).¹ There are several treatment options depending on the severity of the disease, but overall, it is difficult to treat.²

Causes of hepatorenal syndrome

Although the cause of hepatorenal syndrome is not completely clear, it is believed that this disease is onset as a result of liver damage and results in consequent changes in blood flow to organs.¹ This damage can be caused by numerous different mechanisms, such as:^1,2

• Non-alcoholic fatty liver disease
• Alcohol-induced cirrhosis (scarring of the liver due to alcohol)
• Drug-induced damage (like paracetamol overdose) 
• Infections such as Hepatitis B, Hepatitis C or spontaneous bacterial peritonitis (infection of the abdominal fluid surrounding the liver and other organs)

Ultimately, these mechanisms allow for changes in liver functioning and, in particular, the blood flow to your liver and its surrounding organs (often termed splanchnic). Due to this liver disease, the blood pressure of the vein supplying the liver is often raised, which causes other vessels to constrict. Your body then produces chemicals such as nitric oxide, which causes your blood vessels to relax to try and relieve this pressure.1 In doing so, there is a ‘pooling’ of blood within the organs surrounding the liver, which leads to reduced blood flow to the rest of the body.3 This then causes additional compensatory mechanisms aiming to restore blood flow to other organs, which causes constriction of blood vessels supplying the kidneys, which can lead to kidney damage when sustained.² 

Signs and symptoms of hepatorenal syndrome

The hepatorenal syndrome may appear as several non-specific symptoms in combination with those that you would expect from severe liver disease:¹

• Stomach pain
• Tiredness
• Decreased frequency of urination
• Build up of fluid around the stomach
• Swelling or tenderness of the liver or spleen
• Yellowing of your skin or whites of your eyes (jaundice)
• Feeling confused or changes in your mental state (encephalopathy)

Diagnosis

The diagnosis of hepatorenal syndrome does not involve one singular test. It is normally identified by observing a reduction in how well your kidneys work in tandem with the presence of advanced liver disease. The most important element of diagnosis is ensuring the exclusion of any other potential cause of kidney damage, such as structural disease, acute infection or damage due to medication toxicity.²

The specific observations or tests that support a diagnosis of hepatorenal syndrome may include:²

• Identified advanced liver disease such as cirrhosis (can be either acute or chronic) with high pressure within the vein supplying blood to the liver (portal hypertension)
• Blood tests to determine your kidney function by measuring how much creatinine is in your blood or calculation of either your glomerular filtration rate (GFR) or creatinine clearance (indicates how well your kidneys can filter blood)
• The rate of kidney function decline can also help differentiate between type 1 and type 2 hepatorenal syndrome.
• Dramatic reduction in urine production 
• Limited improvement in kidney function despite stopping diuretic medications and increasing plasma volume 

Management and treatment 

Management is mostly supportive and involves treating the underlying precipitating factor (commonly infection in type 1 cases), in combination with trying to minimise the adverse effects of the lack of kidney function. Management in the first instance may involve your medical team being proactive in stopping any (nephrotoxic) medications that may contribute to the further damage of your kidneys, such as:⁴

• NSAIDs (non-steroidal anti-inflammatories) –such as ibuprofen or naproxen
• Diuretic treatments (‘water tablets’ such as furosemide)

Your medical team may also give you medications that change how your blood flows to different organs, as well as offering you a ‘top-up’ of important components that make up your blood (i.e. albumin) to increase the volume of blood reaching the kidney and reduce any damage caused.⁴ 

Although several options of medications have been proposed to help manage hepatorenal syndrome, the medication with the greatest evidence is Terlipressin in alleviating symptoms.  Terlipressin acts to mimic (an ‘analogue’ of) the action of the hormone vasopressin. Terlipressin works by constricting blood flow to some of the ‘splanchnic’ organs to prevent blood pooling.⁴ This then reduces the compensatory mechanisms described above and frees up blood to reach the kidney, which in turn slows the decline in its function. Inserting a transjugular intrahepatic portosystemic shunt (TIPS) by a small surgical procedure may also free up blood from this splanchnic area to the rest of the body.²

Although the above options may provide relief, these are often only short-lived, with the only permanent option for treatment being a liver transplant.⁴ A liver transplant may not be a suitable option for many people, so your risks and background must be heavily weighed up by your medical team before this would be considered. 

Liver transplantation works to cure hepatorenal syndrome by replacing the faulty liver with a healthy one. As liver damage and the linked consequences play a major role in causing dysfunction to the kidneys, replacement of the liver acts to correct these blood flow issues and kidney damage.⁴ It must be noted that a liver transplant does present itself with some risks.

Complications

Hepatorenal syndrome can cause major lasting disability, and if not treated effectively, it can cause death. However, even if managed promptly and effectively, some of the complications of the disease may have profound effects long after the condition has been treated.^1,2

The most significant complication of the disease is kidney damage. The damage caused by your kidneys being starved of blood has the potential to be permanent and in some cases only partially reversible.² In the acute stages, the main concerns caused by kidney damage will be the buildup of toxins within the blood and the difficulty in regulating your body’s electrolytes.⁵ Electrolytes such as potassium may rise to dangerous levels where in excess they can cause fatal changes in your heart rate and rhythm.⁶ In the longer term (even following a liver transplant), irreversible damage to your kidneys may lead to issues such as chronic kidney disease or kidney failure, which may lead to a whole host of problems including:⁶ 

1. Bone disease 
2. Difficulty maintaining the correct levels of electrolytes in your blood 
3. Trouble regulating your blood’s pH (how acidic it is); 
4. Anaemia 
5. The need for dialysis or kidney transplant in severe cases.

Complications associated with treatment may be related to either:

1. Liver transplant – complications may result during the procedure itself, such as concerning changes in blood pressure, excessive bleeding or the formation of blood clots.⁷
2. Medications, such as terlipressin, may cause adverse effects such as changes to your heart rhythm, increased risk of sepsis, or problems with your lungs.⁸ 

Each treatment option will carry its risks, which your medical team will closely evaluate, monitor and mitigate where possible. You should consult your medical team for any specific advice regarding treatment options and potential risks that may be associated.  

Summary

Hepatorenal syndrome is kidney damage linked to liver disease, with many of its symptoms overlapping. Symptoms could be non-specific or related to liver and kidney damage. Being aware of the symptoms of this condition and seeking medical attention promptly, when appropriate, is the best way to ensure effective treatment. 

Diagnosis involves multiple investigations, including blood tests and radiological investigations. It is important to rule out other causes of kidney damage. Treatment includes medications for supportive management. A liver transplant has the potential to be curative in the disease compared to other management options that focus on improving symptoms.