hepatorenal syndrome; acute kidney injury in cirrhosis

Etiology

• liver failure
  • terminal hepatic cirrhosis
  • alcoholic hepatitis
  • acute Wilson's disease
• pre-renal hypoperfusion
  • diuretics
  • gastrointestinal bleeding
  • paracentesis
• toxic agents that damage both the liver & kidney
  • carbon tetrachloride
  • leptospirosis
  • amyloidosis
  • methoxyflurane
• vasculitis

Epidemiology

• occurs in 40-50% of patients with terminal cirrhosis
• generally develops in a hospital setting
• some degree of functional renal impairment occurs in 1/2 of patients with cirrhosis & ascites

Pathology

• liver failure resulting in renal hypoperfusion
• endothelin levels are 10 X normal
• leukotriene abnormalities suggested
• activated sympathetic nervous system
• activated renin-angiotensin axis
• splanchnic vasodilation & a decrease in systemic vascular resistance results in effective circulating volume depletion, renal vasoconstriction & hypoperfusion
• shunting of renal plasma flow from cortical to medullary segments
• transition to acute tubular necrosis is possible
• recovery occurs in about 10% of patients
• histology does NOT suggest primary renal disease

Clinical manifestations

• ascites
• portal hypertension
• jaundice
• progressive azotemia & oliguria
• hypotension/low blood pressure
• esophageal varices may be present

Diagnostic criteria

• major criteria*
  • acute or chronic liver disease with advanced hepatic failure & portal hypertension
    • cirrhosis with ascites
  • low glomerular filtration rate
    • serum creatinine > 1.5 mg/dL
    • creatinine clearance < 40 mL/min
    • diagnosis of acute kidney injury
      • increase in serum creatinine of >0.3 mg/dL within 48 hours
      • increase in serum creatinine of >50% within 7 days
  • absence of
    • treatment with nephrotoxic agents
    • shock
    • infection
    • significant recent fluid lo
  • no sustained improvement of renal function after discontinuation of diuretics &
    • administration of 1.5 L of normal saline
    • administration of albumin (1 g/kg body weight daily)
  • proteinuria < 500 mg/dL, urine RBC < 50 cells/HPF, & no ultrasonographic evidence of obstruction or renal parenchymal disease
• minor criteria**
  • urine volume < 500 mL/day
  • urine Na+ < 10 meq/L
  • urine osmolality > plasma osmolality
  • urine RBC < 50/hpf
  • serum [Na+] < 130 meq/L

* must be present for diagnosis ** based on criteria of low GFR & avid Na+ retention

Laboratory

(in addition to above)

• low serum sodium: hyponatremia
• high serum potassium: hyperkalemia
• low serum albumin: hypoalbuminemia
• high urine sodium in the absence of diuretics suggests another diagnosis
• increased serum creatinine (>1.5 mg/dL)
  • diminished GFR (<50 mL/min)
• increased serum urea (>30 mg/dL)
• urine creatinine, fractional excretion of Na+ (FENA) < 1%
• high plasma renin activity
• low plasma osmolality, high urine osmolality

Diagnostic procedures

• diagnostic paracentesis if ascites

Complications

• mortality is high (59%)

Differential diagnosis

• prerenal azotemia

Management

• supportive measures
  • discontinue diuretics & other potentially offending agents
  • optimized central & renal hemodynamics
  • volume expansion with IV albumin
    • assess component of prerenal azotemia (first line)
    • IV albumin useful for anti-inflammatory effects
  • sodium restriction, restrict free water if hyponatremia
  • vasocontriction
    • terlipressin + epinephrine first line
      • terlipressin may be given through a peripheral line
    • norepinephrine may delay mortality (1st line agent in U.S.)
    • terlipressin facilitates reversal of hepatorenal syndrome & may improve mortality, but increases risk of serious events
    • combination of octreotide + midodrine + vasopressin
      • conflicting evidence regarding efficacy
    • dobutamine (NEJM)
    • if no benefit of maximum dose of vasopressor in 4 days, further benefit unlikely
  • low dose (renal) dopamine
  • high doses of spironolactone (Aldactone)
• hemodialysis
  • if patient does not respond to octreotide + midodrine or norepinephrine
  • hyperkalemia
  • metabolic acidosis
  • pulmonary edema refractory to medical therapy
  • symptoms of uremia
  • drug intoxication
• surgery
  • LeVeen shunt
  • liver transplantation is treatment of choice
• prognosis: 3-6 month survival is ~ 20-40%
• prevention:
  • IV albumin in patients with cirrhosis & spontaneous bacterial peritonitis reduces incidence of hepatorenal syndrome
  • predisolone + pentoxifylline may reduce incidence of hepatorenal syndrome in patients with alcoholic hepatitis

More general terms

• liver disease
• acute renal failure (ARF)
• syndrome

Additional terms

• peritoneal venous shunt; LeVeen shunt