Makindo Medical Notes

About

• Hepatorenal Syndrome (HRS): A severe form of acute kidney failure occurring in patients with advanced liver disease and ascites. It is a life-threatening complication commonly associated with cirrhosis, alcoholic hepatitis, or fulminant liver failure.
• HRS is now classified using the **International Club of Ascites (ICA)** system, aligning with the Acute Kidney Injury (AKI) framework for a more nuanced understanding of renal dysfunction in liver disease.

Classification

The new ICA classification integrates traditional Type 1 and Type 2 HRS into a more detailed system based on the severity and progression of kidney dysfunction, facilitating earlier detection and tailored management.

• HRS-AKI (Hepatorenal Syndrome - Acute Kidney Injury):
  • Characterized by a rapid increase in serum creatinine, following AKI criteria.
  • Subdivided into:
    • Stage 1: Increase in serum creatinine ≥0.3 mg/dL within 48 hours or ≥1.5 times baseline within 7 days.
    • Stage 2: Further elevation of serum creatinine by ≥2 times baseline.
    • Stage 3: Serum creatinine >4.0 mg/dL or initiation of renal replacement therapy.
• HRS-CKD (Hepatorenal Syndrome - Chronic Kidney Disease):
  • Represents stable, long-term impairment of renal function.
  • Associated with diuretic-resistant ascites and persistent renal dysfunction.

Aetiology

• Nitric Oxide (NO): Excessive production leads to splanchnic vasodilation, reducing systemic vascular resistance and effective arterial blood volume.
• Splanchnic Vasodilation: Decreases effective blood volume, triggering compensatory renal vasoconstriction to maintain blood pressure.
• Renal Vasoconstriction: Reduces renal blood flow, causing oliguria and acute kidney injury without structural kidney damage.
• Systemic Inflammation: Elevated inflammatory cytokines contribute to vasodilation and renal dysfunction.

Clinical Features

• Oliguria: Significant reduction in urine output, often less than 500 mL per day.
• Hypotension: Persistently low blood pressure due to decreased systemic vascular resistance.
• Signs of Chronic Liver Disease: Jaundice, ascites, hepatic encephalopathy, and other manifestations alongside renal symptoms.
• Electrolyte Imbalances: Hyponatremia and hyperkalemia may be present.

Comparing Classifications

The table below contrasts the traditional classification (Type 1 and Type 2) with the new ICA classification (HRS-AKI and HRS-CKD).

Investigations

• Laboratory Tests:
  • Rising Urea and Creatinine: Indicative of renal failure without significant structural kidney damage.
  • No Proteinuria: Helps differentiate HRS from intrinsic renal diseases.
  • Low Urinary Sodium: Typically <10 mmol/L, reflecting sodium conservation by the kidneys.
  • Urine/Plasma Osmolarity: Ratio usually >1.5, indicating concentrated urine despite impaired function.
• Imaging Studies:
  • Ultrasonography: To rule out other causes of renal dysfunction such as obstruction.
  • Renal Doppler Studies: May show reduced renal blood flow.
• Exclusion of Other Causes: Essential to confirm HRS by ruling out intrinsic renal diseases.

Management

• Albumin Infusions: Expand plasma volume and improve renal perfusion. Typical dosing: 1 g/kg on the first day, followed by 20-40 g/day as needed.
• Terlipressin: A vasopressor counteracting splanchnic vasodilation to improve renal blood flow. Standard dosing: 2 mg every 4-6 hours, titrated based on response.
• Nitric Oxide Inhibitors: Agents like midodrine may be combined with other vasoconstrictors to enhance efficacy.
• Diuretics: Often discontinued to prevent further intravascular volume depletion.
• Haemodialysis: Generally not indicated unless severe electrolyte imbalances or volume overload are present.
• Liver Transplantation: The definitive treatment offering the best chance for renal recovery and overall survival.
• Vasoconstrictor Therapy: Combination of vasopressors (e.g., terlipressin) and albumin is first-line therapy for HRS-AKI.
• Transjugular Intrahepatic Portosystemic Shunt (TIPS): May be considered in select cases to reduce portal hypertension, though its role in HRS is limited.

Type II Hepatorenal Syndrome (HRS)

• Characterized by less severe but more chronic renal dysfunction compared to Type I.
• Primary features include diuretic-resistant ascites, where standard diuretic therapy fails, leading to persistent fluid accumulation.
• Renal dysfunction progresses more slowly, allowing for potential stabilization with appropriate medical management.
• Despite a gradual course, Type II HRS carries significant morbidity and a poor prognosis without liver transplantation.
• Treatment strategies include vasoconstrictors, albumin infusions, and consideration of liver transplantation for eligible patients.

References

• Hepatorenal Syndrome: Pathophysiology, Diagnosis, and Management - NCBI
• Hepatorenal Syndrome - American Liver Foundation
• Diagnosis and Management of Hepatorenal Syndrome - Gastroenterology Journal
• New Classification of Hepatorenal Syndrome: The International Club of Ascites Recommendations - AASLD