Updated: 1/29/2019

Hepatorenal Syndrome

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Snapshot
  • A 55-year-old man is admitted to the hospital due to fatigue, malaise, and weakness in the setting of poorly controlled cirrhosis. His symptoms began approximately one week prior to presentation, where he began to increase his alcohol intake after receiving news of the passing of his brother. Medical history is significant for cirrhosis due to chronic alcohol use disorder and hepatitis C infection. On hospital day 7, he was found to have a creatinine of 3.7 mg/dL (his creatinine was 1.2 mg/dL upon admission) and has significantly decreased urine output. He was not started on any nephrotoxic medications and post-renal obstruction has been ruled out. On physical exam, he is confused, has ascites, palmar erythema, jaundice, and gynecomastia. He is admitted into the intensive care unit to receive intravenous epinephrine and albumin.
Introduction
  • Clinical definition
    • kidney failure in the setting of liver disease
      • 2 types of hepatorenal syndrome (HPS)
        • type 1 HPS
          • severe form that has a rapid rise in serum creatinine (2-fold increase in < 2 weeks)
        • type 2 HPS
          • a less severe form that classically presents with ascites that is unresponsive to diuretics
  • Epidemiology
    • risk factors
      • acute or chronic liver disease
      • low mean arterial blood pressure
      • dilutional hyponatremia
      • urinary sodium retention (severe)
  • Etiology
    • can occur spontaneously
    • can be precipitated by spontaneous bacterial peritonitis (SBP)
  • Pathogenesis
    • portal hypertension triggers splanchnic arterial vasodilatation
      • this in turn decreases systemic vascular resistance which decreases renal perfusion
        • decreased renal perfusion leads to a decline in glomerular filtration rate (GFR) and sodium excretion
  • Associated conditions
    • portal hypertension secondary to
      • cirrhosis
      • severe alcoholic hepatitis
    • fulminant hepatic failure
  • Prognosis
    • depends on the type of hepatorenal syndrome
      • however, prognosis is typically poor without treatment
Presentation
  • Symptoms
    • fatigue
    • malaise
    • dysgeusia
  • Physical exam
    • stigmata of chronic liver disease such as
      • palmar erythema
      • spider nevi
      • scleral icterus
      • gynecomastia
      • hepatosplenomegaly
      • ascites
      • caput medusae
      • atrophic testes
    • oliguria may be seen
Studies
  • Labs - abnormalities secondary to pre-renal pathology  
    • progressive rise in serum creatinine
      • type 1 hepatorenal syndrome
        • a rapid rise in serum creatinine (2-fold increase in < 2 weeks)
      • type 2 hepatorenal syndrome
        • less severe
    • low sodium excretion rate
  • Making the diagnosis
    • a diagnosis of exclusion
Differential
  • Glomerulonephritis
  • Vasculitis
  • Diabetic nephropathy
  • Drug-induced nephrotoxicity
    • e.g., from aminoglycosides, diuretics, and contrast agents
Treatment
  • Medical
    • norepinephrine with albumin
      • indication
        • in critically ill patients with hepatorenal syndrome (HPS)
    • terlipressin with albumin or midodrine with octreotide and albumin
      • indication
        • in non-critically ill patients with HPS
        • the midodrine, octreotide, and albumin combination is typically given when terlipressin is not available
  • Operative
    • dialysis
      • indication
        • typically performed in patients who are waiting for liver transplantation
    • liver transplantation
      • indication
        • definitive treatment
Complications
  • Worsening liver failure that can result in
    • hepatic encephalopathy
    • jaundice
    • coagulopathy
 

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Questions (3)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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