AKI & Hepatorenal Syndrome (HRS)

Jacob Lee

Pathophysiology

  • Hypothesis: portal hypertension causes increased production of vasodilators from splanchnic endothelium and defective response to vasoconstrictors which leads to vasodilation causing renal hypoperfusion and injury

Definitions

  • HRS-non-AKI 
    • HRS-AKD: cirrhosis with ascites + criteria for AKI not met; refers to eGFR < 60 mL/min for < 3 months 
    • HRS-CKD: above but ≥ 3 months 
  • HRS-AKI: what we refer to as hepatorenal syndrome (below)

Evaluation

  • Step 1: Exclude other obvious causes of renal injury 
    • Workup: BMP, UA with microscopy, urine electrolytes (urine sodium, creatinine AND urea), UPCR (urine protein-creatinine ratio), renal ultrasound 
    • Suggestive of HRS-AKI: FeNa <0.2, FeUrea <20 (most sensitive diagnostic measure). UNa <20 
  • Step 2: 
    • STOP all nephrotoxins (diuretics, non-selective beta blockers, NSAIDs, ACE/ARBs, antihypertensives, vasodilators) 
    • START volume expansion with albumin 1g/kg/day (up to a max of 100 g/day) x2 days (note, those with albumin >3.5 are at higher risk of pulmonary edema thus 2nd dose discussed as team on rounds)

HRS-AKI Diagnostic Criteria

  • HRS-AKI 
  • Cirrhosis with ascites 
  • Rise in Cr ≥0.3 within 48h or rise in Cr ≥50% within 7 days, OR UOP <0.5 mL/kg/hr for 6 hours 
  • No improvement in creatinine or UOP after volume expansion 
  • Absence of other causes of AKI 
  • Notably, absence of proteinuria (<500 mg/d), absence of hematuria (<50 RBCs per HPF) do not automatically disqualify HRS as a diagnosis per 2024 guidelines

Management

  • Vasoconstricting Agents: 
    • Terlipressin: Approved for use at VUMC in Transplant Candidates only. Start at 0.85mg q6h Increase dosage to maximum 1.7mgq6h at 24 hours if serum creatinine has not decreased by 25% 
    • Norepinephrine (+/- albumin 50 g/day). Can be administered on stepdown unit; Central access required if > 15 mcgs/min. Start NE gtt at 3mcg/min. If UOP is <200 or MAP <10mm Hg from baseline, increase by 3 mcg/min every 4 hours until achieving UOP or MAP goal 
    • Guidelines recommend 20-40g Albumin/day with vasoconstrictors, we typically give 25- 50g
  • When to discontinue vasoconstrictors: 
    • Serum creatinine within 0.3 of baseline, no improvement in serum creatinine after 48-72h with max tolerated doses, initiation of RRT, ≥14 days duration, liver transplant, adverse reaction 
  • Continue to hold diuretics/nephrotoxic agents 
  • LVP is still generally considered safe even in HRS if indicated by tense ascites. This can be attending specific and would confirm prior to performing 
  • RRT: Dialysis can be considered for those who fail to respond to pharmacologic therapy, 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
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