22: Hepatorenal Syndrome



Overall Bottom Line


  • HRS is a potentially reversible functional renal insufficiency in patients with cirrhosis, advanced liver failure and portal hypertension.
  • There is no specific diagnostic test for HRS. The diagnosis is based on monitoring and interpreting renal function in a patient with liver insufficiency.
  • Type 1 HRS is defined by doubling of the initial serum creatinine level to >2.5 mg/dL or 50% reduction of the initial 24-hour creatinine clearance to <20 mL/minute in less than 2 weeks.
  • Type 2 HRS is characterized by impairment in renal function leading to serum creatinine level >1.5 mg/dL that does not meet the criteria for type 1 HRS.
  • Without appropriate therapy the prognosis is extremely poor with a median survival time from the time of diagnosis of approximately 2 weeks for patients with type 1 HRS and 6 months for patients with type 2 HRS.
  • Drug therapy is based on systemic arterial vasoconstrictors combined with volume expansion.
  • Liver transplantation is the best treatment option with a 3-year survival rate of approximately 70%.






Section 1: Background



Definition of disease



  • HRS is a potentially reversible functional renal insufficiency in patients with cirrhosis, advanced liver failure and portal hypertension in the absence of shock or an intrinsic parenchymal kidney disease.


Epidemiology



  • Eighteen percent of patients with decompensated cirrhosis develop HRS within 1 year of decompensation and 39% within 5 years.
  • The incidence of HRS in patients with liver cirrhosis who are admitted to the hospital because of ascites formation is 7–15%.
  • In acute hepatic failure due to alcoholic hepatitis HRS occurs in approximately 27% of patients.


Etiology



  • HRS most often occurs in patients with advanced cirrhosis, but may also complicate acute liver failure.
  • Most cases of type 1 HRS are elicited by precipitating factors, such as:

    • Infections (SBP is the most common infection precipitating HRS).
    • Viral, alcoholic, toxic or ischemic hepatitis superimposed on cirrhosis.
    • Major surgical procedures.
    • Gastrointestinal bleeding, intensive treatment with diuretics and diarrheal disease may elicit HRS, but more often cause prerenal insufficiency.


Pathogenesis



  • Changes in endogenous vasoactive systems with marked renal vasoconstriction while at the same time extrarenal arteriolar vasodilatation, decreased systemic resistance and arterial hypotension predominate (Algorithm 22.1).
  • The most important pathophysiologic change in HRS is a marked intrarenal arterial vasoconstriction with reduced renal perfusion and reduced glomerular filtration rate.

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Algorithm 22.1 Pathogenesis of hepatorenal syndrome


c22-fig-5001

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Predictive factors



  • Predictive factors for the development of HRS in non-azotemic patients with liver cirrhosis and ascites:

    • Previous episodes of ascites.
    • Absence of hepatomegaly.
    • Poor nutritional status.
    • Moderately reduced glomerular filtration rate (>50 mL/minute).
    • Moderately increased BUN (<30 mg/dL).
    • Moderately increased serum creatinine (≤1.5 mg/dL).
    • Low serum Na+.
    • High serum K+.
    • Low urinary Na+-excretion.
    • Low plasma osmolality.
    • High urine osmolality.
    • High plasma renin activity.
    • Low arterial pressure.
    • Reduced free water clearance following a water load.
    • Increased plasma norepinephrine.
    • Esophageal varices.


Section 2: Prevention



Screening



  • Every patient with liver cirrhosis admitted to the hospital should have serial determinations of serum creatinine levels and/or creatinine clearance.


Prevention



  • Avoid and/or eliminate precipitating factors (see “Etiology” in Section 1).
  • Patients with spontaneous bacterial peritonitis should be treated with albumin IV since this has been shown to decrease the incidence of HRS and improve survival.
  • Pentoxifylline (400 mg PO three times a day for 28 days) has been shown to reduce the incidence of HRS in patients with severe (Maddrey Score >32) alcoholic hepatitis (only one randomized trial).


Section 3: Diagnosis






Clinical Pearls


  • There are no specific laboratory tests or imaging methods for the diagnosis of HRS.
  • Diagnostic criteria for HRS have been developed by the International Ascites Club (see “Diagnostic criteria (International Ascites Club)”.
  • The diagnosis is based on interpreting serial serum creatinine levels and/or creatinine clearance in patients with severe hepatic insufficiency.
  • HRS that does not meet the criteria of type 1 HRS is classified as type 2 HRS.





Differential diagnosis



  • Most cases of renal dysfunction in cirrhosis are functional in nature. The differential diagnosis encompasses functional circulatory disturbances, obstructive lesions and pre-existing structural changes in the kidneys (acute-on-chronic kidney disease).

    • Pre-renal failure:

      • volume deficiency (e.g. vomiting, diarrhea, excessive administration of diuretics).

    • Acute tubular necrosis:

      • circulatory shock, severe bacterial infections, nephrotoxic drugs (NSAIDS, aminoglycosides).

    • Post-renal failure

      • urinary tract obstruction (e.g. stones, tumors).

  • Monitoring renal function after withdrawal of diuretic treatment with subsequent intravenous volume expansion allows for important diagnostic conclusions. In pre-renal failure, renal function rapidly improves, while in HRS this measure remains without effect.





Differential diagnostic criteria for kidney dysfunction in cirrhosis
















Diagnosis Definition
Acute kidney injury Rise in serum creatinine of >50% from baseline or a rise in serum creatinine by ≥26.4 μmol/L (≥0.3 mg/dL) in less than 48 hours
HRS type 1 is a specific form of acute kidney injury
Chronic renal disease Estimated glomerular filtration rate of <60 mL/minutes for more than 3 months calculated using the Modification of Diet in Renal Disease 6 (MDRD6) formula
HRS type 2 is a specific form of chronic kidney disease
Acute-on-chronic kidney disease Rise in serum creatinine of >50% from baseline or a rise in serum creatinine by ≥26.4 μmol/L (≥0.3 mg/dL) in less than 48 hours in a patient with cirrhosis whose glomerular filtration rate is <60 mL/minute for more than 3 months calculated using the MDRD6 formula








Differential diagnostic parameters in patients with cirrhosis, ascites and renal insufficiency (serum creatinine >3 mg%)*


w9781118517345c22-1.jpg

* The parameters traditionally used to differentiate acute tubular necrosis from functional renal failure (urinary sodium excretion and urine: plasma osmolality ratio) are of very limited value in patients with cirrhosis and ascites. Possibly, urinary levels of β2-microglobulin are markers of tubular damage in cirrhosis.





Typical presentation



  • The presentation is that of a patient with advanced liver cirrhosis (see Chapter 19).
  • Most patients have:

    • Diuretic resistant ascites.
    • Circulation which is hyperdynamic with high cardiac output and reduced total vascular resistance.

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Aug 12, 2016 | Posted by in GASTROENTEROLOGY | Comments Off on 22: Hepatorenal Syndrome

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