How to manage non-oliguric acute kidney injury (AKI) in patients with cirrhosis?

Management of Non-Oliguric AKI in Cirrhotic Patients

Immediately discontinue all diuretics, beta-blockers, and nephrotoxic medications while administering albumin 1 g/kg/day (maximum 100g) for two consecutive days, regardless of whether the patient meets hepatorenal syndrome criteria, as this approach achieves 80% treatment response rates and allows differentiation of AKI phenotypes. 1, 2

Immediate Initial Management (First 48 Hours)

Medication Review and Withdrawal

• Stop ALL diuretics immediately, even in non-oliguric patients, as urine output in cirrhosis does not reliably reflect GFR due to avid sodium retention 1
• Discontinue beta-blockers (not just diuretics alone), as EASL guidelines specifically recommend stopping both drug classes 1, 3
• Withdraw all nephrotoxic agents including NSAIDs, ACE inhibitors, ARBs, aminoglycosides, and vasodilators 1, 3

Infection Screening (Mandatory and Urgent)

• Obtain blood cultures, urine cultures, and chest radiography immediately, as infection is present in 25-40% of hospitalized cirrhotic patients with AKI 4, 5, 6
• Perform diagnostic paracentesis if any ascites is present to exclude spontaneous bacterial peritonitis, which is a critical precipitant of HRS-AKI 1, 4
• Initiate empirical antibiotics before culture results if infection is strongly suspected, as bacterial infections drive inflammatory cascades that directly worsen kidney injury 4, 6

Volume Assessment and Albumin Administration

• Administer 20% albumin solution at 1 g/kg body weight (maximum 100g) on Day 1, followed by 20-40 g/day on Day 2 for all patients with AKI Stage ≥1B (creatinine ≥1.5 mg/dL) 1
• This 2-day albumin challenge serves dual purposes: treating prerenal AKI and differentiating HRS-AKI from other phenotypes 1, 2
• Monitor closely for pulmonary edema during albumin administration using continuous pulse oximetry, as fluid overload occurred in 8.5% of patients in clinical trials 1, 7

Staging-Based Management Algorithm

AKI Stage 1A (Creatinine increase ≥0.3 mg/dL but <1.5 mg/dL)

• Close monitoring with serum creatinine measurement every 2-4 days during hospitalization 1, 3
• Continue risk factor management (medication withdrawal, infection treatment) 1
• Do NOT initiate vasoconstrictors at this stage, as most experts have concerns about early terlipressin use when creatinine <1.5 mg/dL 1
• Volume expansion with crystalloids if clinical hypovolemia is suspected (diarrhea, excessive prior diuresis) 1

AKI Stage 1B-3 (Creatinine ≥1.5 mg/dL or ≥2x baseline)

• Implement the 2-day albumin challenge as described above 1, 2
• Reassess after 48 hours of albumin therapy to determine response 1, 2
• If creatinine returns to within 0.3 mg/dL of baseline: continue close monitoring and follow-up every 2-4 weeks for 6 months post-discharge 1, 3
• If creatinine remains elevated after 2 days: proceed to phenotype differentiation 1, 2

Phenotype Differentiation After Albumin Challenge

Patients Meeting HRS-AKI Criteria

HRS-AKI diagnosis requires: creatinine ≥1.5 mg/dL, no response to 2-day albumin challenge, absence of shock, no nephrotoxic drugs, no structural kidney disease on ultrasound, and proteinuria <500 mg/day 1

Initiate terlipressin 0.85 mg IV every 6 hours plus continued albumin therapy 1, 7

• Starting dose: 0.85 mg every 6 hours as slow IV bolus over 2 minutes for Days 1-3 7
• On Day 4: increase to 1.7 mg every 6 hours if creatinine decreased <30% from baseline; discontinue if creatinine is at or above baseline 7
• Median time to terlipressin initiation should be approximately 2.5 days from AKI diagnosis when following this algorithm 2
• Response rate to terlipressin is 61-76% when initiated early 1, 7, 2

Patients NOT Meeting HRS-AKI Criteria (Most Common: 74%)

The majority of patients not responding to albumin will have acute tubular necrosis (ATN) or other intrinsic AKI phenotypes, not HRS-AKI 2

• Continue supportive care without vasoconstrictors, as 70% of non-HRS patients respond to supportive measures alone 2
• Urinary NGAL >220 μg/g creatinine suggests ATN rather than HRS (AUROC 0.78) 1, 2
• Consider therapeutic paracentesis with albumin if tense ascites is present, as this improves renal function by reducing intra-abdominal pressure 1, 5

Critical Monitoring During Treatment

Respiratory Monitoring (Highest Priority)

• Obtain baseline oxygen saturation before initiating terlipressin and monitor continuously with pulse oximetry 7
• Serious or fatal respiratory failure occurred in 14% of terlipressin-treated patients vs 5% on placebo 7
• Discontinue terlipressin immediately if hypoxia or worsening respiratory symptoms develop 7
• Avoid terlipressin entirely in patients with ACLF Grade 3, as they are at significantly increased risk of respiratory failure 7

Volume Status Monitoring

• Manage fluid overload by reducing or discontinuing albumin and judicious use of diuretics once renal perfusion is restored 7
• Patients with fluid overload are at increased risk of respiratory failure during terlipressin therapy 7

Ischemic Event Monitoring

• Discontinue terlipressin if signs of cardiac, cerebrovascular, peripheral, or mesenteric ischemia develop (occurred in 4.5% of patients) 7
• Avoid terlipressin in patients with history of severe cardiovascular or cerebrovascular disease 7

Special Considerations and Pitfalls

Common Pitfalls to Avoid

• Do not rely on urine output to diagnose or stage AKI in cirrhosis, as oliguria can result from avid sodium retention with preserved GFR, and polyuria can occur from diuretic use 1
• However, recognize that urine output <0.5 mL/kg for >6 hours is associated with higher mortality when it does occur 1
• Never use eGFR equations (MDRD, CKD-EPI) in acute settings, as they require steady-state creatinine and are inaccurate in AKI 3
• Do not delay albumin challenge waiting for diagnostic certainty—the 2-day trial itself is both therapeutic and diagnostic 1, 2

Transplant Considerations

• For patients with MELD ≥35 or high transplant priority, carefully weigh risks of terlipressin-related complications (respiratory failure, ischemia) that may make them ineligible for transplantation 7
• Patients with serum creatinine >5 mg/dL are unlikely to benefit from terlipressin 7
• Ninety-day transplant-free survival is negatively associated with MELD-Na, ATN phenotype, HRS-AKI, and elevated urinary NGAL 2

Renal Replacement Therapy

• Consider RRT on an individualized basis for refractory hyperkalemia, severe acidosis, or fluid overload unresponsive to medical management 1, 3
• Only 8% of patients required RRT when the EASL algorithm was properly implemented 2
• Prefer continuous or prolonged intermittent RRT over conventional intermittent hemodialysis in hemodynamically unstable patients 4

Prevention Strategies

• Administer albumin with large-volume paracentesis (>5L removed) 1
• Provide antibiotic prophylaxis for spontaneous bacterial peritonitis in high-risk patients 1
• Give antibiotics with gastrointestinal bleeding episodes 1
• Monitor serum creatinine and electrolytes regularly in outpatients on diuretics 1