What is hepatorenal syndrome?

Hepatorenal Syndrome Definition

Hepatorenal syndrome (HRS) is a functional renal failure that occurs in patients with advanced cirrhosis and ascites, characterized by renal vasoconstriction in the absence of structural kidney damage, with diagnostic criteria including serum creatinine >1.5 mg/dL, no improvement after albumin administration, absence of shock, no nephrotoxic drug exposure, and no evidence of parenchymal kidney disease. 1, 2

Pathophysiology

• Splanchnic arterial vasodilation is the primary event leading to reduced effective arterial blood volume and decreased mean arterial pressure, creating a hyperdynamic circulatory state 3
• Arterial underfilling triggers activation of the sympathetic nervous system and renin-angiotensin-aldosterone system (RAAS), causing renal vasoconstriction 1, 3
• Impaired cardiac function due to cirrhotic cardiomyopathy contributes to inadequate cardiac output to compensate for vasodilation 3
• Increased synthesis of vasoactive mediators affects renal blood flow and glomerular microcirculation 1, 3
• Systemic inflammation and bacterial translocation aggravate the circulatory and hemodynamic alterations 4

Diagnostic Criteria

• Required criteria for HRS diagnosis:
  • Cirrhosis with ascites 1
  • Serum creatinine >1.5 mg/dL 2
  • No improvement of serum creatinine after 2 consecutive days of diuretic withdrawal and plasma volume expansion with albumin (1 g/kg body weight) 1, 2
  • Absence of shock 1, 2
  • No current or recent use of nephrotoxic drugs (e.g., NSAIDs, aminoglycosides, iodinated contrast media) 1, 2
  • Absence of parenchymal kidney disease as indicated by:
    • No proteinuria (>500 mg/day) 1
    • No microhematuria (>50 red blood cells per high power field) 1
    • Normal findings on renal ultrasonography 1

Classification

• HRS-AKI (formerly Type 1 HRS):

  • Characterized by rapid, progressive renal impairment 1, 2
  • Serum creatinine increasing ≥100% to >2.5 mg/dL in less than 2 weeks 2
  • Poor prognosis with median survival of approximately 1 month if untreated 2
  • Often triggered by bacterial infections, particularly spontaneous bacterial peritonitis 1

• HRS-CKD (formerly Type 2 HRS):

  • Features stable or less progressive impairment in renal function 1, 2
  • More chronic course with better survival compared to HRS-AKI 2

AKI Staging in HRS Diagnosis

• Stage 1: Increase of creatinine ≥0.3 mg/dL up to 2-fold of baseline 1
• Stage 2: Increase in creatinine between 2-fold and 3-fold of baseline 1
• Stage 3: Increase in creatinine >3-fold of baseline or creatinine >4 mg/dL with an acute increase ≥0.3 mg/dL or initiation of renal replacement therapy 1

Differential Diagnosis

• HRS accounts for 15-43% of AKI cases in cirrhotic patients 1
• Other common causes include:
  • Hypovolemia (27-50% of cases) 1
  • Acute tubular necrosis (14-35% of cases) 1
• Biomarkers such as urinary neutrophil gelatinase-associated lipocalin (NGAL) may help differentiate HRS from acute tubular necrosis 1

Clinical Implications and Management

• Early diagnosis is critical as HRS carries high mortality 1
• First-line treatment for HRS-AKI is terlipressin plus albumin 2
• Alternative treatments include midodrine plus octreotide plus albumin, or norepinephrine plus albumin 2
• Liver transplantation is the definitive treatment for both forms of HRS 1, 2
• Prevention strategies include:
  • Albumin infusion with antibiotics when treating spontaneous bacterial peritonitis 1, 2
  • Norfloxacin (400 mg/day) to reduce HRS incidence in advanced cirrhosis 2
  • Avoiding nephrotoxic drugs in patients with advanced cirrhosis 2

Prognosis

• Untreated HRS-AKI has a median survival of approximately 1 month 1, 2
• High MELD scores and HRS-AKI are associated with very poor prognosis 1
• Response to vasoconstrictors with reduction in serum creatinine is associated with improved survival 5