Skip to content

Hepatorenal Syndrome

Garren Montgomery


  • Portal HTN causes shear stress on portal vessels -> endothelium release of vasodilators -> splanchnic vasodilation and reduced effective blood volume (decreased MAP) -> RAAS activation -> sodium and water retention and severe renal vasoconstriction

  • Bacterial translocation (as seen in SBP) -> increased circulating pro-inflammatory cytokines -> splanchnic vasodilation

  • Definitions:

    • HRS-AKI (formerly type I HRS): Rise in Cr ≥0.3 within 48h, rise in Cr ≥50% within 7 days, OR UOP <0.5 mL/kg/hr for 6 hours
    • HRS-NAKI (“non-AKI”) (formerly type II HRS):
      • HRS-AKD: eGFR<60 for <3 months in absence of other structural causes OR % rise in Cr ≤50% using last available Cr over last 3 months as baseline
      • HRS-CKD: eGFR<60 for ≥3 months in absence of other structural causes
  • Diagnostic Criteria

    • Diagnosis of AKI (see above) without other cause (see below
    • No response or inadequate response at 48 hrs after volume expansion with albumin and withdrawal of diuretics
    • Absence of proteinuria (<500 mg/d), absence of hematuria (<50 RBCs per HPF), normal renal ultrasound (exclude if patient has known CKD
    • Suggestion of renal vasoconstriction with FeNa <0.2, FeUrea <20 (most sensitive diagnostic measure). UNa <20 is suggestive but not diagnostic given baseline sodium avidity in cirrhosis and inability to calculate FeNa
    • Cut off for ATN in cirrhosis is a FeNa >0.5, rather than 1 in the general population


  • Step 1: Exclude other obvious causes of renal injury such as hypovolemia or ATN

    • Common precipitants of AKI: infection, overdiuresis, GI bleeding, recent LVP without subsequent volume expansion, nephrotoxic drugs/NSAIDs
    • Workup: BMP, UA with microscopy, urine electrolytes (FeNa, FeUrea), urine protein/Cr ratio, renal ultrasound (to assess for chronicity), diagnostic para to rule out SBP
  • Step 2: Diuretic cessation/albumin challenge

    • STOP all diuretics, beta blockers, NSAIDs, ACE/ARBs, anti-hypertensives, vasodilators, nephrotoxins
    • START volume expansion with albumin 1g/kg/day (up to a max of 100 g/day) x2 days
  • Step 3: Diagnosis of HRS

    • If no other clear cause of AKI is identified and SCr has not improved after 48 hours of diuretic cessation and volume expansion, proceed promptly to vasopressor treatment


  • Pharmacologic therapies (in order of preference):

    • Terlipressin (± albumin 50g/day, unless there is evidence of volume overload). Most effective medication based on randomized clinical trials, NOW FDA APPROVED and approved for use at VUMC in Transplant Candidates only. Titration is done based on creatinine response.
    • Alternatively, consider Norepinephrine (± albumin 50 g/day)
      • Requires central access (PICC vs triple lumen) but can be administered on stepdown unit
      • Guidelines recommend NE to be dosed at 0.5-3 mg/hr. Would ask fellow, attending or pharmacist for baseline. VUMC protocol for ICU and stepdown:
      • Start NE gtt at 3mcg/min. If UOP is <200 or MAP <10mm Hg from baseline, increase by 3 mcg/min every 4 hours
  • Continue to hold diuretics. LVP is still generally considered safe even in HRS if indicated by tense ascites (account for albumin repletion from LVP and HRS protocol). This can be attending specific and would confirm prior to performing

  • Therapy is generally continued until HRS is reversed or the hepatology attending deems it refractory to medical treatment. (Per guidelines, protocol normally discontinued if Cr remains at pretreatment level or above >4 days)

  • Patients with HRS-NAKI (formerly type II HRS) may respond to the above therapies, but recurrence of renal dysfunction after withdrawal of vasoconstrictors is the norm and thus current guidelines do not recommend them for this scenario

  • RRT: Dialysis can be considered for those who fail to respond to pharmacologic therapy, particularly ONLY as a bridge to liver transplant. Decision to initiate should be individualized

  • Liver transplant: The best and most definitive treatment regardless of response to pharmacologic therapy

Simultaneous liver-kidney transplant:

  • HRS often resolves with LT alone. Indications for kidney transplant are usually for patients with severe chronic renal dysfunction or on RRT. Must consult transplant nephrology.

  • Criteria for SLKT:

    • eGFR <60 for >30 days AND latest eGFR <30
    • eGFR <25 for >6 consecutive weeks with a documented eGFR q7 days
    • Metabolic syndromes and polycystic disease
  • Can qualify for safety net kidney transplant after liver transplant if eGFR <20 2-12 months post-operatively (would be at higher priority than the rest of the kidney transplant list)