Epidemiology & Risk Factors
- Advanced cirrhosis w/ portal HTN and ascites (most common).
- Acute liver failure.
- Precipitants: SBP, GI bleeding, excessive diuresis, LVP without albumin replacement, nephrotoxic agents (NSAIDs).
- Pathogenesis: Portal HTN -> nitric oxide release -> splanchnic vasodilation -> ↓ effective arterial blood volume -> compensatory activation of RAAS/SNS/ADH -> severe renal vasoconstriction -> ↓ GFR.
Clinical Features
- Signs of portal HTN/cirrhosis: Ascites, jaundice, splenomegaly, caput medusae, spider angiomata.
- Signs of renal dysfunction: Oliguria or anuria, progressive fluid retention.
- Hepatic encephalopathy (asterixis, altered mental status).
- Hypotension (low systemic vascular resistance).
Diagnosis
- Initial Evaluation: Check serum Cr, electrolytes, urinalysis, and renal US (to rule out structural causes).
- Key Diagnostic Criteria:
- Diagnosis of exclusion.
- Cirrhosis with ascites.
- AKI (doubling of Cr or Cr > 1.5 mg/dL over < 2 weeks).
- No improvement after ≥ 48 hours of fluid withdrawal (diuretics held) and albumin challenge (1 g/kg/day). c
- Unlike crystalloids (which easily leak into the peritoneal space, worsening ascites), albumin remains in the intravascular compartment
- For HRS, the splanchnic vasodilation and localized renal vasoconstriction are too severe to be overcome by volume expansion alone
- Absence of shock, nephrotoxic drugs, or parenchymal kidney disease (proteinuria < 500 mg/day, no microhematuria, normal renal US).
- Key Labs:
- Urine Na < 10 mEq/L (indicates intense renal sodium retention). c
- FeNa < 1% (simulates prerenal state).
- Urine osmolality > serum osmolality.
Differential Diagnostics
- Prerenal Azotemia: Differentiated by rapid improvement in renal function following volume expansion with IV fluids/albumin.
- Acute Tubular Necrosis (ATN): Differentiated by urine Na > 40 mEq/L, FeNa > 2%, muddy brown granular casts, and lack of response to albumin.
- Glomerulonephritis: Differentiated by significant hematuria (> 5 RBCs/hpf), RBC casts, and proteinuria > 500 mg/day.
Management
- Immediate/First-Line:
- Discontinue diuretics (Furosemide, Spironolactone) and nephrotoxic drugs.
- Initiate Albumin infusion (1 g/kg on day 1, then 20-40 g/day) + vasoconstrictor therapy.
- Terlipressin (preferred systemic vasoconstrictor; analogue of vasopressin).
- Norepinephrine (alternative if pt in ICU).
- Midodrine (alpha-1 agonist) + Octreotide (somatostatin analogue) (used if Terlipressin is unavailable).
- Refractory/Second-Line:
- TIPS: Reduces portal pressure; used in selected pts as a bridge to transplant.
- Renal replacement therapy (hemodialysis) if pt meets urgent indications (AEIOU) and is a transplant candidate.
- Definitive Therapy:
- Orthotopic liver transplantation (OLT) (only curative treatment).
Complications
- Refractory ascites.
- Severe electrolyte derangements (hyponatremia, hyperkalemia).
- Multi-organ dysfunction syndrome (MODS).
- High short-term mortality (especially HRS-AKI without treatment).