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Hepatorenal Syndrome
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 is often precipitated by events lowering blood pressure. [1]
A number of factors can precipitate hepatorenal syndrome, including infections, alcoholic hepatitis and
bleeding. [2]
Epidemiology [3]
HRS is a common complication of end-stage liver disease. The incidence of HRS is unknown. However, it is
estimated that 35-40% of patients with end-stage liver disease and ascites eventually develop HRS.
Diagnostic criteria for hepatorenal syndrome [4]
HRS is essentially a diagnosis of exclusion - ie there is an absence of other identifiable causes of renal
failure. The diagnostic criteria have been defined as follows:
Criteria for diagnosis of hepatorenal syndrome in cirrhosis
Cirrhosis with ascites.
Serum creatinine >1.5 mg/dL (133 μmol/L).
Absence of shock.
Absence of hypovolaemia as defined by no sustained improvement of renal function (creatinine
decreasing to <133 μmol/L) following at least two days of diuretic withdrawal (if on diuretics), and
volume expansion with albumin at 1 g/kg/day up to a maximum of 100 g/day.
No current or recent treatment with nephrotoxic drugs.
Absence of parenchymal renal disease as defined by proteinuria <0.5 g/day, no micro-haematuria
(<50 red cells/high-powered field), and normal renal ultrasonography.
Reprinted from: Journal of Hepatology vol. 53, No authors listed, EASL clinical practice guidelines on the
management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis, pp397-417,
Epub 2010 Jun 1, ©2010, with permission from Elsevier.
HRS is probably the result of a combination of the following: splanchnic vasodilatation leading to systemic
circulatory dysfunction, activation of the sympathetic nervous system and renin-angiotensin-aldosterone system,
and changes in cardiac output (usually low but is always less than the patient's requirements). In addition there is
enhanced release of vasoactive mediators - eg, thromboxane A2 and endothelin-1. The end result is intrarenal
arteriolar vasoconstriction. [5]
Types of hepatorenal syndrome [1, 4, 5]
HRS has been divided into two types depending on rate of progression:
Type 1 - defined as a doubling of serum creatinine to >221 μmol/L in less than two weeks, ie rapidly
progressing. These patients have a very low glomerular filtration rate (GFR) (<20 ml/minute) and very
poor prognosis. This is usually associated with a precipitating event - eg, variceal bleed, spontaneous
bacterial peritonitis.
Type 2 - defined as a more gradual decline in renal function, associated with sodium retention and
refractory ascites.
Patients with type 2 HRS can go on to develop type 1 HRS following a precipitating event.
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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).
Risk factors
Spontaneous bacterial peritonitis - 30% will develop HRS. [4]
Gastrointestinal (GI) tract bleed.
Superimposed infections - eg, pneumonia.
Diagnosis
This is made after excluding other causes of renal failure in patients with liver failure: [1]
Pre-renal causes (eg, whether there is history of dehydration, over-diuresis, GI fluid loss).
Any history of nephrotoxic drugs.
Whether there is history of shock before renal failure (which would suggest acute tubular necrosis).
Whether there is any proteinuria ± haematuria, suggesting a parenchymal renal disease (renal
ultrasound scan may be helpful) - particularly, glomerulonephritis (associated with hepatitis B/hepatitis
C or chronic alcoholism).
Management [4]
Type 1 HRS
General measures
Admit to hospital - ideally to the high-dependency unit.
Monitor fluid status closely - eg, urine output and CVP monitoring which will help guide fluid
replacement.
Restrict fluids if necessary.
Treat any precipitating infections aggressively. If there is no clear focus of infection, patients should still
be started on broad-spectrum antibiotics - and a full course completed. [4]
Avoid nephrotoxic drugs and stop diuretics.
Splanchnic vasoconstrictors
Start splanchnic vasoconstrictors - eg, terlipressin in combination with albumin replacement.
Terlipressin leads to an increased blood pressure and GFR, through constriction of splanchnic blood
vessels.
Monitor closely for: ischaemic heart disease, arrhythmias, fluid overload and digital ischaemia.
Alternatives include noradrenaline (norepinephrine) or midodrine (unlicensed in the UK) and octreotide,
although at present there is little experience of using these drugs.
Transjugular intrahepatic portosystemic shunt (TIPS)
TIPS is used to reduce ascites in patients with portal hypertension, in those who do not respond to
medical treatment. [6]
It is contra-indicated in severe liver failure, which has limited its use.
Studies have not reported TIPS to be associated with increased survival in type 2 HRS. [7]
Other methods
The best chance of long-term survival would seem to be liver transplantation.
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Renal replacement therapy (RRT) may be necessary - eg, pulmonary oedema, severe hyperkalaemia
or metabolic acidosis not responding to other treatment. Yet there are no data suggesting
improvements in survival in HRS with RRT.
Type 2 HRS
Patients who develop type 2 HRS may need to be admitted and treated as type 1 HRS.
Some patients with type 2 HRS can be treated on an outpatient basis with sodium restriction and
diuretics (eg, spironolactone - monitor for hyperkalaemia).
Elective admissions with repeated paracentesis may be necessary to control gross ascites.
TIPS can be used in refractory cases and may be more feasible than in type 1 HRS. [5]
Liver transplantation [4]
Liver transplantation is the best option for both types 1 and 2 HRS (whether or not they respond to
vasoconstrictors).
Combined kidney and liver transplant may be needed in patients with HRS who require prolonged renal
support (ie >3 months).
Complications
Life-threatening bacterial infections (septicaemia, spontaneous bacterial peritonitis, pneumonia).
Prognosis [4]
HRS is associated with low survival, with an average median survival rate of only three months for type 1 HRS
and six months for type 2 HRS. [1] Liver transplantation in both type 1 and type 2 HRS improves survival, with
rates of 65% in type 1 HRS reported.
Prevention
It may be possible to reduce the incidence of HRS in patients by early administration of albumin
(especially in patients with bacterial peritonitis). [5]
Pentoxifylline and norfloxacin may decrease the incidence of HRS in selected patients but further
studies are needed. [4]
Further reading & references
1. Gines P, Guevara M, Arroyo V, et al; Hepatorenal syndrome. Lancet. 2003 Nov 29;362(9398):1819-27.
2. Egerod Israelsen M, Gluud LL, Krag A; Acute kidney injury and hepatorenal syndrome in cirrhosis. J Gastroenterol Hepatol.
2015 Feb;30(2):236-43. doi: 10.1111/jgh.12709.
3. Al-Khafaji A, Nadim MK, Kellum JA; Hepatorenal Disorders. Chest. 2015 Mar 26. doi: 10.1378/chest.14-1925.
4. Management of Ascites Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome in Cirrhosis ; European Association
for the Study of the Liver (2010)
5. 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.
6. Dundar HZ, Yilmazlar T; Management of hepatorenal syndrome. World J Nephrol. 2015 May 6;4(2):277-86. doi:
10.5527/wjn.v4.i2.277.
7. 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.
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical
conditions. EMIS has used all reasonable care in compiling the information but makes no warranty as to its
accuracy. Consult a doctor or other healthcare professional for diagnosis and treatment of medical conditions.
For details see our conditions.
Original Author:
Dr Huw Thomas
Current Version:
Dr Colin Tidy
Peer Reviewer:
Dr Adrian Bonsall
Document ID:
2254 (v23)
Last Checked:
17/08/2015
Next Review:
15/08/2020
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