Hepatorenal syndrome

1. HEPATORENAL SYNDROME
POSTGRADUATE SEMINAR
DEPARTMENT OF INTERNAL MEDICINE
LAUTECH TEACHING HOSPITAL
BY
DR OYEWUSI D.O.

2. OUTLINES
• INTRODUCTION
• EPIDEMIOLOGY
• HISTORY
• DEFINITION
• CLASSIFICATION
• PATHOPHYSIOLOGY
• DIAGNOSIS
• MANAGEMENT
• PREVENTION
• CONCLUSION

3. INTRODUCTION
• Advance liver cirrhosis from diverse causes is a common condition
presenting in both outpatient and emergency units.it is associated
with many complications among which is renal dysfunction.
• Renal dysfunction is one of the most severe complications of liver
cirrhosis cause of which is multifactorial, occurring in up to 50% of
hospitalized patients.

4. INTRODUCTION
• Within the spectrum of renal dysfunction in patients with liver
cirrhosis, hepatorenal syndrome carries the most ominous prognosis
because it usually denotes a background of severe portal
hypertension and circulatory dysfunction

5. EPIDEMIOLOGY
• AKI occurs in 25% to 50% of cirrhotic patients admitted to the hospital after
an episode of acute decompensation. Prerenal causes include hypovolemia
and HRS-AKI, and together they account for 60% to 70% of all causes of
AKI, with HRS accounting for 11% to 20% of all causes of AKI. Intrinsic renal
causes account for approximately 30% of all causes of AKI in cirrhotic
patients, and include ischeamic inury and acute tubular necrosis, acute
glomerulonephritis and acute interstitial nephritis, where as postrenal
(obstructive) causes are relatively uncommon(<1%)

6. • 2% to 31% of hospitalized cirrhotic patients with AKI do not survive
their admission .One and 12-month mortality rates reported united
states are 58% and 63% respectively.

7. HISTORY
• Frerichs the founder of modern liver pathology reported the presence of oliguria
in patients with ascites in 1877
• Flint noted that in most cases of renal failure in cirrhosis, there were no
significant changes in the kidneys at autopsy.
• In 1956, hecker and Sherlock described renal failure in nine patients with liver
disease characterized by progressive oliguria, very low urinary sodium excretion
hyponatremia but no proteinuria

8. • It was later established that the renal failure was functional since the
kidneys of these patients could be successfully transplanted to other
patients with chronic renal failure and the renal failure was reversible
after liver transplantation.
• In 1967 the hallmark of HRS was found to be severe renal
vasoconstriction.

9. • The term hepatorenal syndrome was first used in 1939 to describe the
occurrence of renal failure after biliary surgery or hepatic trauma. It was
later extended to other types of acute renal failure in liver disease
• In 1996 the international ascites club proposed a new definition and
diagnostic criteria for HRS
• Since then this term as been generally accepted for the functional renal
failure that develops in patients with advance cirrhosis of the liver.

10. DEFINITION AND CLASSIFICATION
Hepatorenal syndrome is defined as a severe complication of end stage
cirrhosis that occurs as a result of reduced renal perfusion, due to
hemodynamic alterations in arterial circulation, as well as overactivity
of the endogenous vasoactive systems.
Hepatorenal syndrome was historically classified into 2 types:

11. • HRS Type 1(Acute): which was defined as rapid deterioration in kidney function over the
course of two weeks. It usually develops following a precipitating event but can occur
spontaneously. Patients are usually very ill with severe jaundice , coagulopathy and liver
failure. This has been renamed as HRS AKI.
• HRS Type 2(chronic): which was characterized by progressive slower course of moderate
renal failure(evolves slowly over weeks to months) and serum creatinine concentration
between 1.5 and 2.5mg/dl.patients with type 2 are usually less ill than those with type
1HRS with a milder degree of jaundice and coagulopathy. Most commonly associated
with refractory ascites. Renamed as HRS CKD.

12. • The main problem with this classification is that it relied on serum creatinine
concentration as the sole factor to classify HRS into type 1 and type 2,
irrespective of the underlying pathology and etiology. As well as the use of an
absolute creatinine value of 2.5mg/dl in diagnosis of AKI.
• This is because serum creatinine is not an accurate measurement in patients with
liver cirrhosis due to low protein intake, loss of muscle mass, diminished hepatic
synthesis of creatinine and an enlarged volume of distribution. All these lower
the level of serum creatinine irrespective of kidney function.

14. PATHOPHYSIOLOGY
• There has been several pathophysiological explanations proposed as
to why HRS AKI occurs in patients with advance cirrhosis and portal
hypertention.
• Splanchnic vasodilation
• Abnormal renal autoregulation
• Abnormal cardiac function in cirrhosis
• Systemic inflammation

16. diagram

17. FACTORS PRECIPITATING HRS
Any condition that causes a further reduction in the effective arterial blood volume can precipitate HRS.
These include:
1. Over diuresis
2. Large volume paracentesis > 5Litres without intravascular colloid replacement in patients with refractory ascitis
3. Gastrointestinal bleeding
Other triggers are conditions that worsen the arterial vasodilation such as
4. Sepsis (especially SBP)
5. Jaundice due to the vasodilatory effect of bile acids

18. CLINICAL FEAUTURES
• Signs and symptoms of background aetiology – liver diseases
• Signs and symptoms of renal disease- HRS
-Reduction in urine output
-Ureamic symptoms
• Signs and symptoms of precipitating factor
Fever, abdominal pain (SBP/ SEPSIS)
Low blood pressure(SHOCK)
Tachycardia
Cold extremities

19. DIAGNOSIS/DIAGNOSTIC CRITERIA
• The diagnostic criteria for HRS were updated by the IAC in 2015 following
the adaptation of uniform nomenclature and diagnostic criteria for AKI
• A trial of diuretic withdrawal, together with intravascular volume
replacement should be done, as this can replenish the effective arterial
blood volume. The intravascular volume replacement can be with blood for
patients that are anaemic or albumin at the dose of 1g/kg of body weight
up to a maximum of 100g/day.

20. DIAGNOSTIC CRITERIA FOR HRS-AKI
1. Cirrhosis and ascites
2. Diagnosis of AKI according to the IAC-AKI criteria
3. No reduction in serum creatinine after at least 48hrs of diuretic
withdrawal and volume expansion with albumin
4. Absence of shock
5. No current or recent treatment with nephrotoxic drugs
6. No evidence of structural kidney injury defined as
• Absence of proteinuria(> 500mg/day)
• Absence of hematuria (>50 rbc/hpf)
• Normal kidney ultrasonography

22. INVESTIGATIONS
Important investigations to be done are :
1. Abdominopelvic scan
2. Renal function test
3. Urinalysis
4. Urine electrolyte
5. Full blood count
6. Blood culture
7. Ascitic fluid m/c/s
Other are investigation to determine the etiology of the liver disease

23. TREATMENT
Treatment of HRS is based on correcting the different aspect of the
pathophysiology, including :
1. Improving the effective blood volume- volume expanders
2. Reducing arterial vasodilation – vasoconstrictors
3. Eliminating portal hypertension - TIPS
4. Correcting liver dysfunction and portal hypertension- liver
transplantation

25. VOLUME EXPANDERS
• Volume expansion done by the use of albumin at a dose of 1g/kg on
the first day and then 20g to 40g/day.
• This is due to the fact that hypoalbuminemia is a common in cirrhosis
secondary to :
• Reduced synthesis
• Dilution from plasma volume expansion
• Intracapillary escape into extra vascular space

26. • Albumin infusion in AKI-HRS suppress sympathetic activity.
Specifically it causes a decrease in plasma norepinephrine reversing
the primary abnormalities in the pathophysiology of liver cirrhosis.
• It has however been shown to be more effective in lowering serum
creatinine when combined with vasoconstrictors in management of
HRS-AKI

27. • Albumin dose should be titrated according to the level of central
venous pressure of up to 10cm of water
• Albumin should be reduced or stopped in the presence of
intravascular volume overload and/or pulmonary oedema

28. VASOCONSTICTORS
• Vasoconstrictors are the mainstay of treatment for patients with AKI-
HRS while awaiting liver transplantation.
Terlipressin
Terlipressin is a vasopressin analogue which causes vasoconstriction of
the splanchnic vessels, fundamental in the pathophysiology of HRS.
This improves the central circulation and reduces renal vasoconstriction

29. • A continous infusion is better tolerated and more effective at lower
doses than IV doses.
• In a three randomized controlled trial done in accessing the effect of
telipressin , reversal of AKI-HRS was observed in 24%-44% without
overall survival benefit.

30. NOREPINEPHRINE AND MIDODRINE:
Systemic vasoconstrictors that raise systemic arterial blood pressure and
improves renal perfusion pressure. This leads to reduced renal
vasoconstriction and improve GFR.
OCTREOTIDE: This an analogue of somatostatin, a hormone involved in
regulation of blood vessel tone in the gastrointestinal tract. Also inhibits
splanchnic vasodilation. Used in combination with midodrine

32. TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC STENT
• TIPS is a prosthesis that can effectively reduce portal pressure.
• TIPS returns a significant part of the splanchnic vascular volume into the
the systemic circulation decreasing the activity of various vasoconstrictor
systems.
• The use of TIPS in the management of AKI-HRS has been shown to lead to
an improvement, but not normalization, of GFR. Efficiency is improved
when used with a vasoconstrictor.

33. LIVER TRANSPLANTATION
• Liver transplantation is the definitive treatment of both AKI-HRS and
chronic type 2 HRS.
• It corrects liver dysfunction and eliminates portal hypertention
• A return to normal kidney function in patients with pre transplant AKI-HRS
of about 50% to 75% is expected.
• The use of living donor liver transplant appears to provide similar results to
cadaveric liver transplant.

34. ROLE OF RENAL REPLACEMENT THERAPY
• Dialysis is frequently indicated to deal with the electrolyte
abnormalities and volume overload prior to liver transplantation.
• Many studies have however shown that the longer a patient is on
dialysis prior to liver transplant the less likely they are to have a
reversal of kidney function.

35. PROGNOSIS
• HRS is associated with a poor prognosis , studies have shown a 2week
mortality of up to 80% in untreated AKI-HRS. In chronic type 2
HRS,the kidney function decline is more gradual but it is also
associated with a poor prognosis with a median survival of 3 to 6
months.

36. PREVENTION
• Primary prevention- health education of patients on prevention of
liver diseases, cessation of alcohol, hepatitis b vaccination
• Secondary prevention-early diagnosis and treatment of liver
diseases
• Tertiary prevention- limitation of complications by preventing
precipitating factors to development of HRS

37. DIFFERENTIALS
1. Prerenal azotemia is the most common cause of renal dysfunction
in hospitalized patient with cirrhosis.
2. Intrinsic kidney diseases occur in approximately one third of
patients with liver disease, most commonly is acute tubular
necrosis.
3. Post renal failure occurs only in <1% of patients with cirrhosis

38. CONCLUSION
• HRS is a form of functional acute kidney injury (AKI) which occurs in patients with end stage liver
cirrhosis and circulatory dysfunction.
• Any condition that causes a further reduction of the effective arterial volume can potentially
precipitate HRS
• In hospitalized patients with cirrhosis , prerenal azotemia is the most common cause of acute
kidney injury. HRS can be considered as form of prerenal azotemia which is not volume
responsive and is seen exclusively in patients with severe liver disease
• Pharmacologic treatment increases survival, but the only definitive treatment is liver
transplantation

39. REFERENCES
1. Management of hepatorenal syndrome Journal of hepatology vol
71,issue 4
2. Hepatoranal syndrome, American society of nephrology
3. EASL Clinical practice guidelines on the management of ascites, SBP
and hepatorenal syndrome in liver failure
4. Nephrology secrets 4th edition