Hepatorenal Syndrome

Aka: Hepatorenal Syndrome, Urohepatic Syndrome, Renal Failure Secondary to Liver Disease, Hepatorenal Failure

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II. Definitions

  1. Hepatorenal Syndrome
    1. Renal Failure due to Hepatic Cirrhosis
    2. Serum Creatinine rises >0.3 mg/dl (or >50% over baseline)
    3. Intrinsic renal disease absent or stable

III. Epidemiology

  1. Less common in Primary Biliary Cirrhosis
  2. Incidence in Cirrhosis with Ascites
    1. One year 18%
    2. Five years: 39%

IV. Pathophysiology

  1. Arterial vasodilation of splanchnic circulation
    1. Results in underfilling of arterial circulation
  2. Renin-Angiotensin System Activation
    1. Results in decreased renal perfusion due to renal vasconstriction

V. Types

  1. Type I Hepatorenal Syndrome
    1. Associated with Spontaneous Bacterial Peritonitis
      1. Occurs in 25% of patients with SBP
    2. Rapid deterioration of Renal Function
      1. Serum Creatinine doubles to >2.5 mg/dl or
      2. Creatinine Clearance <20 ml/minute
    3. Survival
      1. Without treatment: <2 weeks (median)
      2. With Treatment: 10 weeks
  2. Type II Hepatorenal Syndrome
    1. Associated with Diuretic-resistant Ascites
    2. Renal Function declines moderately
      1. Serum Creatinine >1.5 mg/dl
    3. Survival: 3-6 months (median)

VI. Differential Diagnosis

  1. Acute Kidney Injury Causes
  2. Hypovolemia
  3. Shock
  4. Nephrotoxin

VII. Diagnosis

  1. Major Criteria
    1. Liver failure with Portal Hypertension
    2. Decreased Glomerular Filtration Rate (GFR)
      1. Serum Creatinine >1.5 mg/dl or
      2. Creatinine Clearance < 40 ml/min
    3. No alternative causes of Acute Renal Failure
      1. No Nephrotoxins
      2. No shock, Sepsis or Hypovolemia due to excessive diuresis
      3. Urine Protein <500 mg/dl
      4. No parenchymal renal disease by renal Ultrasound
      5. No ureteral obstruction by renal Ultrasound
    4. Renal Failure refractory to measures
      1. Diuretics withdrawn
      2. Volume expansion: 1.5 Liters Normal Saline
  2. Minor Criteria
    1. Urine Volume <500 ml/day
    2. Urine Sodium <10 meq/Liter
    3. Urine Osmolality increased over plasma osmolality
    4. Urine Red Blood Cells <50 per hpf
    5. Serum Sodium <130 mEq/L

VIII. Labs

  1. Pan-culture for Sepsis
    1. Blood Culture
    2. Urine Culture
    3. Ascitic fluid culture (see Paracentesis)
  2. Urinalysis
    1. Evaluate for Hematuria and Proteinuria

IX. Imaging

  1. Renal Ultrasound
    1. Exclude renovascular disease
    2. Exclude Hydronephrosis

X. Management

  1. Consider Intensive Care admission for close monitoring
    1. Monitor and manage fluids, Electrolytes and hemodynamic status
  2. Avoid Nephrotoxins and stop contributing factors
    1. Stop Diuretics
    2. Stop Beta Blockers
    3. Stop NSAIDs
    4. Stop Angiotensin Converting Enzyme Inhibitors (ACE Inhibitors)
    5. Stop Angiotensin Receptor Blockers
    6. Stop vasodilators
  3. Albumin replacement
    1. Administer 1 g/kg/day (maximum dose of 100 g/day) for up to 3 days
    2. May continue albumin at 20 to 40 g/day as needed for Hypotension requiring Vasopressors
  4. Midodrine and Octreotide
    1. Octreotide 100 mcg SQ three times daily AND
    2. Midodrine 5 to 10 mg orally three times daily
    3. Less effective than Norepinephrine in stabilization of Blood Pressure (but may be used in combination)
  5. Hyperkalemia
    1. See Hyperkalemia Management
    2. Sodium Zirconium Cyclosilicate (Lokelma) 10 mg orally three times daily for 48 hours
  6. Vasopressors
    1. Targets
      1. Increase Mean Arterial Pressure >10-15mmHg
      2. Increase Urine Output >200 ml per 4 hours
    2. Preparations: First-Line (preferred)
      1. Norepinephrine
    3. Preparations: Alternatives
      1. Terlipressin
        1. Vasopressor similar to Vasopressin (with longer duration, selective) and FDA approved in 2022
        2. Similar efficacy to Norepinephrine (but does not require a Central Line)
        3. Higher risk of Respiratory Failure and Pulmonary Edema (avoid in hypoxic patients)
        4. Very expensive ($4000/day in 2023)
        5. Dosed IV every 6 hours
    4. References
      1. (2023) Presc Lett 30(1)
      2. Pitre (2022) Crit Care Med 50(10): 1419-29 [PubMed]
      3. Wong (2021) N Engl J Med 384(9): 818-28 [PubMed]
  7. Other management
    1. Consider Hemodialysis
    2. Consider Transjugular Intrahepatic Portosystemic Shunt (TIPS)
    3. Consult for Liver Transplant (consider transfer)

XI. Prognosis

  1. Associated with high short-term mortality

XII. References

  1. Swencki (2015) Crit Dec Emerg Med 29(11):2-10
  2. Swencki (2023) Crit Dec Emerg Med 37(8):4-12
  3. Keating (2022) Am Fam Physician 105(4): 412-20 [PubMed]

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