What is the treatment for acute hepato-renal syndrome?

Treatment of Acute Hepato-Renal Syndrome

Terlipressin plus albumin is the first-line treatment for hepatorenal syndrome with acute kidney injury (HRS-AKI), with terlipressin administered at an initial dose of 1 mg intravenously every 4-6 hours along with albumin at 1 g/kg on day 1 followed by 20-40 g daily. 1

Diagnostic Criteria

• HRS-AKI is diagnosed in patients with cirrhosis with ascites who develop acute kidney injury stage 2 or 3 according to KDIGO criteria, with no response after 2 days of diuretic withdrawal and plasma volume expansion with albumin, absence of shock, no recent nephrotoxic drugs, and no macroscopic signs of structural kidney injury 2
• Serum creatinine is used to diagnose and stage AKI, though it has limitations in cirrhotic patients due to decreased muscle mass, increased distribution volume, and interference with measurement techniques related to elevated bilirubin 1

First-Line Treatment

Vasoconstrictors

• Terlipressin is the vasoactive drug of choice for HRS-AKI, counteracting splanchnic vasodilation to improve renal blood flow and glomerular filtration rate 1
• Initial dosing of terlipressin: 1 mg intravenously every 4-6 hours (total 4-6 mg/day) 1
• If serum creatinine doesn't decrease by at least 25% after 3 days, increase dose to 2 mg every 4-6 hours (maximum 8-12 mg/day) 1
• Alternative administration: continuous IV infusion at initial dose of 2 mg/day, which may reduce adverse effects while maintaining efficacy 1
• Treatment should continue until 24 hours after two consecutive serum creatinine values ≤1.5 mg/dL at least 2 hours apart, or for a maximum of 14 days 1
• FDA restrictions: terlipressin should not be used in patients with serum creatinine ≥5 mg/dL or oxygen saturation <90% 1, 3

Albumin Administration

• Administer albumin at 1 g/kg on day 1 followed by 20-40 g daily during vasoconstrictor therapy 1
• Albumin enhances the effect of vasoconstrictors by improving systemic hemodynamics and increasing cardiac output 1
• Monitor fluid status closely due to risk of pulmonary edema with excessive albumin use 1

Alternative Treatments

When Terlipressin is Unavailable

• Norepinephrine is a reliable alternative to terlipressin in patients with central venous access 2
• Administer norepinephrine as continuous IV infusion at starting dose of 0.5 mg/h, increasing every 4 hours by 0.5 mg/h to maximum 3 mg/h 1
• Target increase in mean arterial pressure by ≥10 mmHg and/or urine output >50 mL/h for at least 4 hours 1
• Midodrine plus octreotide plus albumin is less effective but can be used if terlipressin and norepinephrine are unavailable 1, 2
• Midodrine dosing: start at 7.5 mg and titrate to 12.5 mg orally three times daily 1
• Octreotide dosing: start at 100 μg and titrate to 200 μg subcutaneously three times daily 1

Renal Replacement Therapy

• Consider renal replacement therapy (RRT) for non-responders to vasoconstrictors 1
• Indications for RRT include severe/refractory electrolyte or acid-base imbalance, severe/refractory volume overload, or symptomatic azotemia 1
• Continuous renal replacement therapy (CRRT) is generally better tolerated than hemodialysis in cirrhotic patients, providing greater cardiovascular stability 1

Advanced Interventions

• Transjugular intrahepatic portosystemic shunt (TIPS) may improve renal function in select patients but is often contraindicated due to severe liver failure 1, 2
• Liver transplantation remains the definitive treatment for HRS-AKI 2, 4

Monitoring and Response Assessment

• Monitor serum creatinine, mean arterial pressure, urine output, and oxygen saturation using continuous pulse oximetry during treatment 1, 3
• Response is characterized by progressive reduction in serum creatinine, increase in arterial pressure, and increased urine volume 2
• Adverse effects of vasoconstrictors include ischemic events (cardiac, peripheral, or mesenteric), pulmonary edema, and distal necrosis 1, 3
• Discontinue terlipressin if SpO2 decreases below 90% due to risk of serious or fatal respiratory failure 3

Important Considerations and Pitfalls

• Early initiation of treatment is crucial as higher levels of creatinine are associated with lower response rates 1
• Patients with creatinine >5 mg/dL have low rates of response and are unlikely to benefit from vasoconstrictors 1, 3
• Recurrence of HRS-AKI after treatment cessation may require repeat course of therapy 1
• Always rule out other causes of AKI, particularly infections like spontaneous bacterial peritonitis, before diagnosing HRS-AKI 1, 2
• Avoid nephrotoxic drugs (especially NSAIDs) in patients with advanced cirrhosis 1, 2