A patient with chronic liver disease now presents with acute kidney injury; what are the initial assessment and management steps?

Management of Acute Kidney Injury in Chronic Liver Disease

Immediately discontinue all diuretics, nephrotoxic drugs, NSAIDs, and vasodilators, then administer intravenous albumin 1 g/kg/day (maximum 100 g) for two consecutive days while aggressively searching for and treating infections. 1, 2

Initial Diagnostic Assessment

Define AKI Stage Using ICA-AKI Criteria

• Stage 1: Serum creatinine (sCr) increase ≥0.3 mg/dL within 48 hours OR ≥1.5-1.9 times baseline OR urine output <0.5 mL/kg/h for 6 hours 1
• Stage 2: sCr increase 2.0-2.9 times baseline OR urine output <0.5 mL/kg/h for ≥12 hours 1
• Stage 3: sCr increase ≥3.0 times baseline OR sCr ≥4.0 mg/dL with acute increase ≥0.3 mg/dL OR initiation of renal replacement therapy OR urine output <0.3 mL/kg/h for ≥24 hours 1

Establish Baseline Creatinine

• Use the most recent sCr value within the last 3 months before admission as baseline 1
• If no prior sCr available and admission sCr ≥1.5 mg/dL, use clinical judgment: assume AKI if there is a clearly identifiable precipitating event, or use admission sCr as baseline and monitor for progression 1
• Critical pitfall: Do NOT use MDRD formula to calculate baseline sCr in cirrhotic patients—it is highly inaccurate, particularly in those with ascites 1

Identify AKI Etiology

Perform these investigations immediately:

• Urinalysis and microscopy: Look for hematuria, proteinuria, casts, or pyuria to differentiate functional (prerenal, HRS-AKI) from structural causes (acute tubular necrosis, glomerulonephritis, acute interstitial nephritis) 1, 3
• Diagnostic paracentesis: Mandatory to rule out spontaneous bacterial peritonitis—obtain cell count, culture, and albumin 2
• Blood cultures, urine cultures, chest radiography: Infection is a common precipitant and must be identified early 2
• Review medication list: Identify and stop all nephrotoxic agents, including aminoglycosides, contrast agents, NSAIDs, ACE inhibitors, and diuretics 1, 2

Key distinction: Approximately 50% of AKI in cirrhosis is prerenal, 35% is acute tubular necrosis, and the remainder is HRS-AKI; postrenal causes are uncommon 1

Stage-Specific Management Algorithm

Stage 1 AKI Management

Implement these measures immediately:

1. Medication review: Withdraw ALL diuretics (even if mild fluid overload exists), nephrotoxic drugs, vasodilators, and NSAIDs 1
2. Volume assessment and expansion:
   • If hypovolemia suspected (gastrointestinal bleeding, diarrhea, excessive diuresis): Give albumin, crystalloids, or blood products based on clinical context 1
   • For GI bleeding with AKI: Albumin is preferred over crystalloids 1
3. Infection management: Start broad-spectrum antibiotics immediately if infection is diagnosed or strongly suspected 1

Monitor response within 48 hours:

• If sCr returns to within 0.3 mg/dL of baseline: Continue close monitoring (sCr every 2-4 days during hospitalization, then every 2-4 weeks for 6 months post-discharge) 1
• If AKI progresses to Stage 2 or 3: Escalate to Stage 2/3 management protocol 1

Stage 2 and Stage 3 AKI Management

Escalate treatment immediately:

1. Withdraw diuretics if not already done 1

2. Albumin infusion: 1 g/kg body weight (maximum 100 g) for two consecutive days 1, 2

3. Reassess after 48 hours of albumin therapy:

   • If no response (sCr remains >2 times baseline or continues rising): Proceed to HRS-AKI diagnostic criteria evaluation 1
   • If partial response: Continue supportive care and monitor closely 1

Hepatorenal Syndrome-AKI (HRS-AKI) Diagnosis and Treatment

HRS-AKI diagnostic criteria (must meet ALL): 1

• Cirrhosis with ascites
• Stage 2 or Stage 3 AKI
• No response after 2 consecutive days of diuretic withdrawal and albumin 1 g/kg (max 100 g/day)
• Absence of shock
• No current or recent nephrotoxic drugs
• Absence of structural kidney disease (no proteinuria >500 mg/day, no hematuria >50 RBCs/hpf, normal renal ultrasound)

If HRS-AKI criteria met:

• Start vasoconstrictors: Terlipressin is first-line (not available in US; use norepinephrine or midodrine plus octreotide as alternatives) 2, 4
• Continue albumin: 20-40 g/day in addition to vasoconstrictors 2
• Monitor mean arterial pressure: Early increase in MAP predicts response to terlipressin 4
• Predictors of poor response: High serum bilirubin and lack of early MAP increase 4

If HRS-AKI criteria NOT met (structural kidney disease):

• Manage as acute tubular necrosis or other intrinsic renal disease with supportive care 1, 3
• Consider nephrology consultation for potential kidney biopsy if diagnosis unclear 3

Special Considerations

Spontaneous Bacterial Peritonitis with AKI

• Albumin protocol: 1.5 g/kg within 6 hours of SBP diagnosis, followed by 1 g/kg on day 3 2
• This regimen reduces risk of HRS-AKI and mortality in SBP 2

Renal Replacement Therapy Indications

Consider RRT for: 1, 5

• Severe/refractory hyperkalemia or metabolic acidosis
• Symptomatic uremia (encephalopathy, pericarditis)
• Refractory volume overload despite therapeutic paracentesis
• Stage 3 AKI with sCr >10 mg/dL and oliguria

Prefer continuous renal replacement therapy (CRRT) over intermittent hemodialysis in hemodynamically unstable cirrhotic patients 5

Managing Fluid Overload WITHOUT Diuretics

• Large-volume paracentesis: Remove ascites with albumin replacement (8-10 g per liter removed if >5L) 5, 2
• Do NOT restart diuretics until AKI fully resolves (sCr returns to within 0.3 mg/dL of baseline) 5, 2
• Crystalloids preferentially accumulate in ascites/edema rather than improving renal perfusion—albumin is superior 2

Critical Pitfalls to Avoid

• Never use crystalloids as first-line volume expansion in cirrhotic AKI: They worsen ascites without improving renal perfusion; albumin is the volume expander of choice 2
• Never continue diuretics during AKI, even with significant fluid overload: Manage congestion mechanically with paracentesis 5, 2
• Never miss occult infection: Sepsis is a leading cause of AKI in cirrhosis and requires immediate broad-spectrum antibiotics 2
• Never use hypertonic saline (3%) except for severe symptomatic hyponatremia: It worsens volume overload 2
• Never rely on calculated GFR formulas (MDRD, CKD-EPI) in cirrhotic patients: They grossly overestimate renal function 1

Prognostic Markers

• sCr ≥1.5 mg/dL is the strongest predictor of AKI progression and short-term mortality 1, 2
• Progression through AKI stages (Stage 1→2 or 2→3) strongly correlates with increased mortality 1
• Stage 1A (peak sCr <1.5 mg/dL) has mortality similar to no AKI; Stage 1B (peak sCr ≥1.5 mg/dL) has significantly worse outcomes 1

Liver Transplant Considerations

• Expedite transplant evaluation for all patients with HRS-AKI: Liver transplantation is the definitive treatment 5
• Consider simultaneous liver-kidney transplantation if renal dysfunction persists despite vasoconstrictor therapy or if on RRT for >4-6 weeks 5