Overview
Etiology
Hepatorenal syndrome is associated with portal hypertension due to:
- Cirrhosis
- Severe alcoholic hepatitis
- Metastatic tumors
- Any cause of fulminant liver failure
Classification
There are 2 types of hepatorenal syndrome:
- Type 1: progressive impairment in renal function and a significant reduction in creatinine clearance within 1–2 weeks
- Type 2
- Renal impairment that is less severe than seen in type 1 HRS
- Associated with a better outcome and ascites that is resistant to diuretics
Pathophysiology
- Portal hypertension triggers arterial vasodilation in the splanchnic circulation.
- This causes: ascites → arterial hypovolemia → activation of renin-angiotensin-aldosterone system (RAAS)
- Activation of RAAS causes: renal vasoconstriction → hypoperfusion of the kidneys → oliguria → anuria → progressive kidney failure
Trigger factors are any interventions or conditions that cause arterial hypovolemia:
- Drainage of ascites
- Bacterial infection
- Gastrointestinal bleeding
- Excessive use of diuretics
Clinical Presentation and Diagnosis
Clinical presentation
- New-onset signs of renal failure with no other identifiable cause:
- Oliguria → anuria → acute kidney failure
- In the early phase of HRS, urine output is often normal.
- Signs of water retention:
- Edema
- Ascites
- Pleural effusion
- Signs and symptoms of cirrhosis:
- Jaundice
- Gynecomastia
- Asterixis
Lower extremity edema due to fluid retention in a patient with hepatorenal syndrome
Image: “Itraconazole associated quadriparesis and edema” by National Aspergillosis Centre, Education and Research Centre, University Hospital of South Manchester (Wythenshawe Hospital), Southmoor Road, Manchester M23 9LT, UK. License: CC BY 2.0Diagnosis
- HRS is a diagnosis of exclusion.
- Investigate for other potential causes of renal failure (sepsis, shock, nephrotoxic agents).
- Laboratory evaluation shows renal injury with prerenal azotemia.
- ↑ Serum creatinine > 1,5 mg/dL (> 133 μmol/L)
- ↑ BUN (blood urea nitrogen):creatinine (Cr) ratio (> 20:1)
- No or minimal proteinuria
- Very low urine sodium (< 10–15 mEq/dL)
- Fractional excretion of sodium (FENa) < 1%
Management
The goal of therapy is improvement in liver function.
- Liver transplant is the only curative treatment.
- Treat any acute causes of liver failure.
- Transjugular intrahepatic portosystemic shunt (TIPS) may be used as bridging therapy.
- Pharmacotherapy:
- Terlipressin (vasoconstriction in splanchnic region → reduces portal pressure)
- Midodrine
- Octreotide
- Albumin
- Around 40% of patients with HRS and acute kidney failure do not respond to treatment.
Differential Diagnosis
Pre-renal failure: presents with similar laboratory findings (↑ serum creatinine and ↑BUN:Cr ratio) and similar urine findings (low sodium excretion in urine). Hepatorenal syndrome can be differentiated from pre-renal failure through an IV fluid challenge. Giving fluids improves pre-renal failure but not HRS.
References
- Amin, A. A., Alabsawy, E. I., Jalan, R., & Davenport, A. (2019). Epidemiology, pathophysiology, and management of hepatorenal syndrome. Seminars in nephrology, 39(1), 17–30.
- Mukhtar, A., & Dabbous, H. (2016). Modulation of splanchnic circulation: Role in perioperative management of liver transplant patients. World journal of gastroenterology, 22(4), 1582–1592. https://doi.org/10.3748/wjg.v22.i4.1582