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Hepatorenal Syndrome

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A complication of end-stage liver disease which occurs in patients who have chronic liver dysfunction with cirrhosis and ascites and also in acute liver failure. In hepatorenal syndrome (HRS) there is impaired renal function which occurs secondary to reduced peripheral vascular resistance and low arterial pressure leading to poor renal perfusion. HRS is often precipitated by events lowering blood pressure - e.g. bacterial infections, large volume paracentesis without volume expansion, or haemorrhage (hypovolaemia).1

Epidemiology

HRS is a common complication but there are no recent data on the prevalence or incidence.

Diagnostic criteria for HRS2
  • Intrarenal arteriolar vasoconstriction.
  • Systemic circulatory dysfunction caused by extra-renal vasodilatation. This varies according to the vascular bed for example, the splanchnic bed may be dilated where as the cerebral bed is vasoconstricted. This may enhance the development of encephalopathy. Cardiac output may be low, normal or high but is always less than the patients requirements.
  • Plasma volume expansion does not improve renal failure.
Types of HRS1,2

HRS has been divided into 2 types depending on rate of progression:

  • Type 1 - defined as a doubling of serum creatinine to >221 μmol/l in less than 2 weeks. These patients have a very low GFR (<20 mL/min) and very poor prognosis.
  • Type 2 - defined as a more gradual and more moderate renal failure with ascites being the most predominant feature.
Presentation

Patients with ascites and other signs of severe liver disease (jaundice, bleeding disorders, malnutrition, stigmata of chronic liver disease) develop renal failure (oligouria or just increasing serum creatinine levels). There is salt and water retention with increased ascites and peripheral oedema - although pulmonary oedema is uncommon. Hyponatraemia is almost universally present (dilutional hyponatraemia); hyperkalaemia is common (and should be aggressively treated).

Diagnosis

This is made after excluding other causes of renal failure in patients with liver failure:1

  • Pre-renal causes (e.g. a history of dehydration, over diuresis, gastrointestinal fluid loss)?
  • Any nephrotoxic drugs?
  • Any history of shock before renal failure (which would suggest acute tubular necrosis)?
  • Any proteinuria ±haematuria? - suggests a parenchymal renal disease (renal USS may be helpful) - particularly glomerulonephritis (associated with Hepatitis B/C or chronic alcoholism).
Management
  • Admit to hospital, restrict fluid and monitor electrolytes.
  • Treat any precipitating infections aggressively.
  • Start vasoconstrictors e.g. terlipressin and iv albumin.
  • Terlipressin leads to an increased blood pressure and glomerular filtration rate.
  • Transjugular intrahepatic portosystemic shunt (TIPS) are used to reduce ascites in patients with portal hypertension in those who do not respond to vasoconstrictors (but is contraindicated in severe liver failure). It may not be associated with increased survival in type 2 HRS.3
  • Best chance of long term survival would seem to be liver transplantation.
  • Renal replacement therapy may be necessary e.g. pulmonary oedema, severe hypokalaemia or metabolic acidosis not responding to other treatment.
  • Type 2 HRS can be treated as an outpatient with sodium restriction and diuretics (e.g. spironolactone - monitor for hyperkalaemia). The role of vasoconstrictors has not been confirmed. Repeated paracentesis may be necessary to control gross ascites and TIPS can be used in refractory cases.2
Complications

Life threatening bacterial infections (septicaemia, spontaneous bacterial peritonitis, pneumonia).

Prognosis

HRS is associated with a low survival - less than 10% for type 1 HRS. Type 2 HRS has a comparatively longer median survival but this is about 6 months.1

Prevention

It may be possible to reduce the incidence of HRS in patients by administering iv albumin (especially in patients with bacterial peritonitis).2,4


Document references
  1. Gines P, Guevara M, Arroyo V, et al; Hepatorenal syndrome. Lancet. 2003 Nov 29;362(9398):1819-27. [abstract]
  2. Salerno F, Gerbes A, Gines P, et al; Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007 Sep;56(9):1310-8. Epub 2007 Mar 27.
  3. Gines P, Uriz J, Calahorra B, et al; Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis. Gastroenterology. 2002 Dec;123(6):1839-47. [abstract]
  4. Sort P, Navasa M, Arroyo V, et al; Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med. 1999 Aug 5;341(6):403-9. [abstract]
Acknowledgements EMIS is grateful to Dr Gurvinder Rull for writing this article and to Dr Huw Thomas for earlier versions. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2009.
DocID: 2254
Document Version: 21
DocRef: bgp24831
Last Updated: 20 Nov 2008
Review Date: 20 Nov 2010

The authors and editors of this article are employed to create accurate and up to date content reflecting reliable research evidence, guidance and best clinical practice. They are free from any commercial conflicts of interest. Find out more about updating.

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