• Disease Overview
  • Synonyms
  • Subdivisions
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • Resources
  • References
  • Programs & Resources
  • Complete Report

Hepatorenal Syndrome


Last updated: May 15, 2015
Years published: 1989, 1990, 1999, 2007, 2008, 2012, 2015


NORD gratefully acknowledges Thomas A. Gonwa, MD, Professor of Medicine, Mayo Clinic College of Medicine, Chairman, Department of Transplantation, Mayo Clinic, Florida, for assistance in the preparation of this report.

Disease Overview

Hepatorenal syndrome (HRS) is a form of impaired kidney function that occurs in individuals with advanced liver disease. Individuals with hepatorenal syndrome do not have any identifiable cause of kidney dysfunction and the kidneys themselves are not structural damaged. Therefore, hepatorenal syndrome may be referred as a “functional” form of kidney impairment. In fact, if the kidney of an individual with hepatorenal syndrome were to be transplanted into an otherwise healthy individual, it would function normally. Hepatorenal syndrome is classified into to two distinct types. Type I is a rapidly progressive condition that leads to renal failure; type II does not have a rapid course and progresses slowly over weeks to months.

Although the hepatorenal syndrome occurs in individuals with liver disease, the exact cause of the condition is unknown. Researchers have noted that blood circulation is abnormal in individuals with hepatorenal syndrome. The arteries that circulate oxygenated blood from the lungs to the rest of the body (systemic circulation) widen in contrast to the arteries of the kidney, which narrow causing a decrease in the blood flow through the kidney. Many affected individuals also have high blood pressure of the branches of the portal vein (portal hypertension), the main vein that carries blood from the intestines to the liver.

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  • hepato-renal syndrome
  • HRS
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  • No subdivisions found
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Signs & Symptoms

Individuals with hepatorenal syndrome will have a variety of nonspecific symptoms including fatigue, abdominal pain, and a general feeling of ill health (malaise). Affected individuals also have symptoms related to advanced liver disease including the accumulation of fluid in the abdomen (ascites), yellowing of the skin and the whites of the eyes (jaundice), an enlarged spleen (splenomegaly) and an enlarged, extremely tender liver (hepatomegaly).

Hepatorenal syndrome type I is characterized by a rapid decrease in kidney function. The kidneys act as a filtration system removing unwanted substances and excess fluid from the body. Symptoms of decreasing renal function include the accumulation of excess watery fluid in the spaces between the tissues and organs causing swelling of these areas (edema), dramatically decreased urination, and the presence of increased nitrogenous waste products such as creatinine and BUN in the blood (azotemia). Hepatorenal syndrome type I can progress to life-threatening renal failure within days.

Individuals with hepatorenal syndrome type I are more likely to suffer from hepatic encephalopathy, a condition that occurs when the liver fails to breakdown (metabolize) certain substances in the body. These substances travel through the bloodstream to the brain with toxic effects. Hepatic encephalopathy may cause confusion, drowsiness, recognizable changes in judgment and other intellectual processes, and other psychological alterations. It also is more likely to occur with acute liver failure due to any cause.

Hepatorenal syndrome type II causes renal dysfunction that generally progresses much slower than it does in type I. Affected individuals are less likely to develop jaundice and usually do not develop hepatic encephalopathy. Individuals with hepatorenal syndrome type II often develop accumulation of fluid in the abdomen (ascites) does not respond to treatment with diuretics, which are drugs that help remove excess fluid from the body. This finding is referred to as diuretic-resistant ascites. It can occur over weeks to months with a slow rise of BUN and Creatinine.

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The exact cause of hepatorenal syndrome is unknown. It occurs in individuals with advanced liver disease, especially individuals who have scarring and dysfunction of the liver (cirrhosis). The characteristic finding in individuals with hepatorenal syndrome is narrowing (constriction) of the blood vessels that feed the kidneys (renal vasoconstriction), which results in decreased blood flow to the kidneys, eventually impairing kidney function.

The reason that renal vasoconstriction occurs is unknown. Researchers believe that the complex interaction of several different factors is involved including high blood pressure of the main blood vessels of the liver (portal hypertension), abnormalities in the physical factors that govern blood flow (systemic hemodynamics), the activation of substances that cause blood vessels to narrow (vasoconstrictors) and suppression of substances that cause blood vessels to widen (vasodilators).

Researchers have also determined that cirrhotic cardiomyopathy may also contribute to the development of hepatorenal syndrome in some individuals. Cirrhotic cardiomyopathy refers to the abnormal functioning of the heart in individuals with scarring of the liver (cirrhosis). Cirrhotic cardiomyopathy results in decreased cardiac outflow (heart failure) and abnormal widening of certain arteries in the body.

In some individuals with hepatorenal syndrome, certain ‘triggers’ can be identified that make it more likely for individuals with liver disease to developed impaired kidney function (hepatorenal syndrome). There triggers are called precipitating factors. The most common precipitating factor is spontaneous bacterial peritonitis (SBP), an infection of the thin membrane (peritoneum) that lines the abdominal cavity. SBP is a known complication in individuals with ascites and cirrhosis. Other common triggers are acute blood loss from the gastrointestinal tract (GI bleeding), low blood pressure and infection from any cause.

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Affected populations

Hepatorenal syndrome affects males and females in equal numbers. The exact incidence of hepatorenal syndrome is unknown. It is estimated to occur in approximately 8-10 percent of individuals with the accumulation of fluid in the abdomen (ascites) and cirrhosis. Although it is most common in individuals with advanced cirrhosis and ascites, hepatorenal syndrome has also occurs in individuals with other forms of liver disease including fulminant hepatic failure.

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A diagnosis of hepatorenal syndrome is made based upon a thorough clinical evaluation, a detailed patient history, and a variety of specialized tests. The International Ascites Club, an organization dedicated to encouraging scientific research into advanced cirrhosis, has established criteria for a diagnosis of hepatorenal syndrome.

The major criteria are: the presence advanced liver failure with portal hypertension; high levels of creatine (an organic acid); the absence of other causes of renal failure such as bacterial infection, shock, and the use of drugs that are toxic to the kidneys; no improvement in renal function with the withdrawal of diuretics and expansion of plasma with albumin (a protein made in the liver which is low in patients with liver disease); and low levels of protein in the urine with no evidence of a disease of the urinary disease (uropathy) or parenchymal renal disease.

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Standard Therapies


The only curative therapy for individuals with hepatorenal syndrome is a liver transplant, which corrects both liver disease and associated impaired renal function. Even after successful liver transplantation, patients who had hepatorenal syndrome beforehand may not fully recover their kidney function. A small percentage may go on to permanent damage requiring dialysis. Much research is ongoing to determine which patients will recover and which may not. Those who may not recover may need a kidney transplant with their liver transplant. However, due to a limited number of donors and long waiting lists, a liver transplant is not always feasible. For patients who develop hepatorenal syndrome with acute liver failure and not cirrhosis, recovery from hepatorenal syndrome can occur if the liver recovers. However, individuals with hepatorenal syndrome requiring dialysis or suffering from advanced kidney failure for 6-8 weeks before receiving a liver transplant, may require a kidney transplant with their liver transplant, as kidney function may not recover.

Individuals with liver disease and the hepatorenal syndrome who receive a liver transplant have a lower success rate than in individuals with liver disease and normal kidney function who receive a liver transplant. Therefore, many of the therapies used to treat hepatorenal syndrome are done to improve kidney function in individuals eligible for a liver transplant.

For individuals awaiting a transplant, several therapies to maintain kidney function may be used. Paracentesis is a surgical procedure that removes the excess fluid from the abdomen (ascites). Under carefully controlled conditions, this procedure may benefit some affected individuals. In addition, avoiding diuretics (which can worsen kidney function), maintaining electrolyte balance, and promptly treating infection may also be necessary.

In 2022, terlipressin (Terlivaz) was approved by the U.S. Food and Drug Administration (FDA) as a treatment option to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney failure. Terlipressin is in the class of drugs known as systemic vasoconstrictors (drugs that cause the blood vessels to narrow).

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Clinical Trials and Studies

Several therapies for hepatorenal syndrome have been explored in recent years including drug therapy, a transjugular intrahepatic portosystemic shunt (TIPS), and renal replacement therapy.

Other systemic vasoconstrictors have been studied to treat individuals with hepatorenal syndrome including ornipressin, midodrine, octreotide, and norepinephrine.

A non-surgical procedure known as transhepatic portosystemic shunts or TIPS has been used to treat several individuals with hepatorenal syndrome. During this procedure, a small metal device called a stent is placed into the liver to improve blood flow. The procedure has been successful in reversing kidney dysfunction in individuals with hepatorenal syndrome. TIPS can lower elevated blood pressure within the portal veins (portal hypertension) – a finding that researchers believe plays a key role in the development of kidney dysfunction in individuals with liver disease. More research including proper clinical study is necessary to determine the long-term safety and effectiveness of TIPS for the treatment of individuals with hepatorenal syndrome.

Hemodialysis and continuous renal replacement therapy have also been reported as potential treatment options for individuals with hepatorenal syndrome. However, these therapies are only supportive and not curative. More research is necessary to determine the safety, effectiveness and feasibility of these potential therapies for individuals with hepatorenal syndrome.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]

For information about clinical trials sponsored by private sources, contact:

For information about clinical trials conducted in Europe, contact:

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Hepatorenal Syndrome Resources

Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder.

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Gonwa TA. Hepatorenal Syndrome and Liver Transplantation. In Ascites, Hyponatremia and Hepatorenal Syndrome: Progress in Treatment. Frontiers of Gastrointestinal Research. Vol. 28. Basel: Karger; 2011:198-207.

Hiang HK, Marquez M, Wong F, Renner EL. Pretransplant Type 2 hepatorenal syndrome is associated with persistently impaired renal function after liver transplantation. Transplantation  2015 epub.

Wong F, Leung W, Al Beshir M, et al. Outcomes of patients with cirrhosis and hepatorenal syndrome Type I treated with liver transplantation. Liver Transplantation 2015; 21: 300-307.

Gonwa TA, Wadei HM. Kidney disease in the setting of liver failure: core curriculum 2013. Am J Kidney Dis. 2013 Dec; 62(6):1198-212.

Angeli P, Gines P. Hepatorenal syndrome, MELD score and liver transplantation: an evolving issue with relevant implications for clinical practice. Journal of Hepatology 2012;57:1135-1140.

Davenport A, Ahmad J, Al-Khafaji A, et al Medical management of hepatorenal syndrome. Nephrol Dial Transp 2012; 27: 34-41.

Gonwa TA, Wadei HM. The challenges of providing renal replacement therapy in decompensated cirrhosis. Blood Purification. 2012;33:144-148.

Wong F. Recent advances in our understanding of hepatorenal syndrome. Nat. Rev Gastroenterol. Hepatol. 2012; 9:382-391.

Wadei HM, Gonwa TA. Hepatorenal syndrome in the Intensive Care Unit. J Inten Care Med.2013;28:79-82.

Sanyal AJ, Boyer T, Garcia-Tsao G, et al. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology. 2008;134:1360-1368.

Turban S, Thuluvath PJ, Atta MG. Hepatorenal syndrome. World J Gastroenterol. 2007;13:4046-4055.

Ruiz-del-Arbol L, Monescillo A, Arocena C, et al. Circulatory function and hepatorenal syndrome in cirrhosis. Hepatology. 2005;42:439-447.

Bhimma R. Pediatric Hepatorenal Syndrome. Medscape. http://emedicine.medscape.com/article/907429-overview  Updated: Mar 19, 2015. Accessed May 12, 2015.

Devuni D. Hepatorenal Syndrome.Medscape. http://emedicine.medscape.com/article/178208-overview Updated: Dec 14, 2014. Accessed May 12, 2015.

Nadim MK, Kellum JA, Davenport A, et al. Hepatorenal syndrome: the 8th international consensus conference of the Acute Dialysis Quality Initiative (ADQI) group. Critical care 2012, 16:R23 http://ccforum.com/content/16/1/R23 Accessed May 12, 2015.

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