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GI & hepatology

Hepatorenal syndrome

HRS-AKI: cirrhosis + ascites + KDIGO AKI after 48 h off diuretics + albumin 1 g/kg/day, no shock, no nephrotoxins, no structural kidney disease (bland urine, normal US).

Andie Gong5 min6 questions2 trials

HRS-AKI is a diagnosis of exclusion

Portal hypertension → splanchnic vasodilation (NO, prostaglandins) → low effective arterial blood volume → RAAS / ADH / SNS → renal vasoconstriction (; ; ; ). Not every rising creatinine in cirrhosis is HRS — ATN, hypovolemia, and obstruction are more common.

HRS-AKI criteria
  1. 1

    Cirrhosis with ascites

    Advanced hepatic failure and portal hypertension. Classic type 1 was Cr >2× baseline and >2.5 mg/dL in <2 weeks; type 2 was slower (1.5–2.5) with diuretic-resistant ascites. Modern language is HRS-AKI vs HRS-CKD.

  2. 2

    KDIGO AKI

    Cr up ≥0.3 mg/dL in 48 h, or ≥1.5× baseline in 7 days, or UOP <0.5 mL/kg/h for 6 h.

  3. 3

    No structural kidney disease

    Proteinuria <500 mg/day, <50 RBC/HPF, normal renal US. Muddy-brown casts do not automatically exclude HRS-AKI. FENa <0.1% and FEUrea <21% support the physiology but FENa is also low in prerenal azotemia.

  4. 4

    Albumin challenge, no shock, no nephrotoxins

    Hold diuretics. Albumin 1 g/kg/day (max 100 g) × 48 h. No , no ongoing nephrotoxins, alternative AKI treated or excluded. Failure to improve is the last piece of the definition.

Precipitants: SBP > other infection, GI bleed, post-LVP fluid shifts, alcohol-associated hepatitis. Prevention: albumin in SBP; primary SBP prophylaxis when indicated.

  • Stop diuretics, NSBBs, ACE inhibitors/ARBs, vasodilators, NSAIDs, and other nephrotoxins. Tap for SBP. Urine sediment, FENa, FEUrea, renal ultrasound.
  • Differential: (bleed, sepsis, pancreatitis), dehydration, ATN (contrast, bile-cast nephropathy), AIN (antibiotics, NSAIDs, PPI), obstruction, GN (IgA, MPGN, cryoglobulin).

Albumin, then a vasoconstrictor

Response = Cr within 0.3 mg/dL of baseline, or Cr <1.5 if no baseline. If volume overload is already the problem and prerenal physiology is unlikely, you may skip the full albumin challenge and start a vasoconstrictor — extra volume can preclude terlipressin.

Terlipressin first-line (CONFIRM)

  • Only FDA-approved HRS-AKI agent. V1a agonist.
  • Start 0.85 mg IV q6 h via peripheral IV with continuous O2 monitoring (needs GI/renal approval in many hospitals).
  • MAP up 10–15 mmHg or UOP up 50% is a good sign. Adjunct albumin 25 g/day if volume allows.
  • Day 4: Cr down ≥30% → continue; <30% → 1.7 mg IV q6 h.
  • Reversal: two Cr values ≥2 h apart within 0.3 of baseline (or <1.5). Stop vasoactives 24 h after the second qualifying Cr.
  • No reversal by day 14: stop, talk transplant / RRT / palliation.

When terlipressin is the wrong drug

  • (): better HRS reversal, more respiratory failure — boxed warning.
  • Contraindications: Cr >5, SpO2 <90%, pregnancy, already on HD, decompensated HF/ACS, mesenteric or limb ischemia, actively listed for transplant in some pathways, ACLF grade 3 (three severe organ failures).
  • Stop immediately if SpO2 <90%. Abdominal pain, nausea, diarrhea, ischemia.
  • ICU alternative: norepinephrine 0.5–3 mcg/min (max ~10), titrate to MAP +10 mmHg, usually central access.
  • If neither available: midodrine + octreotide + albumin remains the historical floor cocktail — several algorithms have dropped it.

Bridge to a liver — not a new kidney

  • Liver transplant is the only cure. Vasoconstrictors are a . Discuss TIPS in selected patients who reverse or who have refractory ascites without severe HE.
  • RRT is supportive in transplant candidates or selected reversible insults — not a destination therapy for HRS.
  • Hold NSBBs during hypotensive HRS; restart later if MAP recovers and variceal prophylaxis is still needed.