What is the role of spironolactone (Aldactone) in patients with Acute-on-Chronic Liver Failure (ACLF) and Hepatorenal Syndrome (HRS)?

Spironolactone in ACLF with Hepatorenal Syndrome

Spironolactone is not recommended for patients with Acute-on-Chronic Liver Failure (ACLF) and Hepatorenal Syndrome (HRS) due to the risk of worsening renal function and electrolyte abnormalities. 1

Pathophysiology and Management of HRS in ACLF

HRS is a serious form of renal dysfunction in patients with cirrhosis and ascites, and is an important component of ACLF syndrome. The condition is characterized by:

• Functional renal impairment without structural kidney disease 2
• Hemodynamic alterations and inflammatory changes 2
• High short-term mortality in ACLF patients 3

First-Line Treatment Approach for HRS in ACLF

Current guidelines recommend the following management strategy:

• Initial management: After withdrawing diuretics and treating precipitating factors, administer IV albumin at 1g/kg (maximum 100g/day) for 48 hours 1
• Vasoconstrictors with albumin: For patients with Stage 2 or greater HRS-AKI without contraindications 1
• Terlipressin: First-line vasoconstrictor (0.5-2.0 mg IV q6h or continuous infusion) for hospitalized patients with Stage 2 or greater HRS-AKI without ACLF-3 or major cardiopulmonary disease 1
• Norepinephrine: Alternative to terlipressin, preferred in patients with shock 1

Why Spironolactone Should Be Avoided in HRS-AKI

Spironolactone should be avoided in HRS-AKI for several reasons:

• Worsening renal function: Spironolactone can further compromise already impaired renal function in HRS 1
• Electrolyte disturbances: Risk of hyperkalemia is significant in patients with renal dysfunction 1
• Ineffective in HRS: Spironolactone acts on the distal tubule and is ineffective in the hemodynamic alterations of HRS 1
• Current guidelines: AASLD practice guidance specifically recommends withdrawing diuretics (including spironolactone) as the first step in managing AKI in cirrhosis 1

Evidence from Heart Failure Studies (Cautionary Parallel)

While not directly studying HRS, evidence from heart failure studies with kidney dysfunction provides important cautionary information:

• Patients with reduced ejection fraction and advanced CKD (eGFR <45 ml/min) had higher risk of 30-day and 1-year readmissions when treated with spironolactone 4
• Risk was particularly high in patients with eGFR <15 ml/min 4
• Careful monitoring is required when using aldosterone antagonists due to risk of hyperkalemia and worsening renal function 1

Definitive Treatment for HRS in ACLF

• Liver transplantation: The definitive treatment for HRS-AKI in cirrhosis 1
• Renal replacement therapy: For patients who fail pharmacotherapy and are awaiting liver transplantation 1
• Palliative care: For non-responders to pharmacotherapy who are not liver transplant candidates 1

Monitoring and Special Considerations

• Patients with HRS-AKI require close monitoring of renal function and electrolytes 1
• Serum sodium <125 mmol/L is an indication to stop diuretics including spironolactone 1
• Patients with ACLF and HRS should be considered for ICU admission, especially with sepsis and liver or coagulation failures 1

In conclusion, while spironolactone is a valuable diuretic in managing ascites in stable cirrhotic patients, it should be discontinued in patients who develop HRS-AKI in the setting of ACLF, as it may worsen renal function and lead to dangerous electrolyte abnormalities.