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Hepatorenal: Meaning, Syndrome and Treatment

Hepatorenal refers to the relationship between the liver and kidneys. Hepatorenal syndrome is a severe kidney disorder occurring as a complication of advanced liver disease.

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Things worth knowing about "Hepatorenal"

Hepatorenal refers to the relationship between the liver and kidneys. Hepatorenal syndrome is a severe kidney disorder occurring as a complication of advanced liver disease.

What Does Hepatorenal Mean?

The term hepatorenal is derived from the Latin words hepar (liver) and renalis (relating to the kidneys). It describes the functional and anatomical relationship between the liver and the kidneys. In clinical medicine, the term is most commonly used in the context of hepatorenal syndrome (HRS) – a life-threatening complication of severe liver disease in which acute kidney failure develops without any primary kidney disease being present.

Causes

Hepatorenal syndrome typically occurs in patients with advanced liver cirrhosis, acute liver failure, or alcoholic hepatitis. The underlying mechanisms include:

Severely impaired liver function leading to dysregulated blood circulation
Pronounced dilation of blood vessels in the abdominal area (splanchnic vasodilation)
Reduction in effective blood volume reaching the kidneys
Activation of the renin-angiotensin-aldosterone system (RAAS) as a compensatory response
Intense constriction of the renal blood vessels, drastically reducing kidney perfusion

Common triggers include bacterial infections (e.g., spontaneous bacterial peritonitis), large-volume paracentesis (drainage of abdominal fluid) without adequate volume replacement, and gastrointestinal bleeding.

Types of Hepatorenal Syndrome

HRS Type 1 (HRS-AKI)

Type 1 is the acute, rapidly progressive form, characterized by a rise in serum creatinine of more than 50% within just a few days. Without treatment, this form carries a very poor prognosis and requires immediate intensive care management.

HRS Type 2 (HRS-NAKI)

Type 2 progresses more slowly and is frequently associated with refractory ascites (fluid accumulation in the abdomen that does not respond to diuretics). Kidney function is impaired but more stable than in Type 1.

Symptoms

The symptoms of hepatorenal syndrome are wide-ranging and reflect both the underlying liver disease and the developing kidney failure:

Significantly reduced urine output (oliguria to anuria)
Fluid accumulation in the abdomen (ascites) and legs (edema)
Yellowing of the skin and eyes (jaundice)
Confusion and altered consciousness (hepatic encephalopathy)
Nausea, vomiting, and general weakness
Elevated kidney markers in the blood (creatinine, urea)

Diagnosis

Hepatorenal syndrome is diagnosed by exclusion, meaning other causes of kidney failure must first be ruled out. Typical diagnostic steps include:

Laboratory tests: serum creatinine, electrolytes, liver function tests, full blood count
Urinalysis to exclude intrinsic kidney disease
Ultrasound of the kidneys and liver (sonography)
Exclusion of hypovolemia through a volume challenge test (intravenous albumin infusion)
Exclusion of nephrotoxic substances (e.g., NSAIDs, contrast agents)

According to current criteria from the International Ascites Club (IAC), HRS is confirmed when serum creatinine does not sufficiently decrease after two days of albumin infusion and no alternative cause of kidney failure can be identified.

Treatment

Treatment of hepatorenal syndrome aims to stabilize kidney function and address the underlying liver disease. Key therapeutic measures include:

Vasoconstrictive medications: Terlipressin in combination with albumin is the standard therapy and leads to improvement in kidney function in a proportion of patients.
Albumin infusions: To stabilize circulation and improve effective kidney perfusion.
Renal replacement therapy: In cases of severe kidney failure, dialysis may be required as a bridging measure.
Transjugular intrahepatic portosystemic shunt (TIPS): Can reduce portal pressure and improve kidney function in selected cases.
Liver transplantation: The only potentially curative treatment. Following a successful transplant, kidney function recovers in many cases.

Prognosis

Hepatorenal syndrome, particularly Type 1, is associated with high mortality. Without treatment, median survival for Type 1 is less than two weeks. With modern drug therapy and especially after liver transplantation, survival rates can be significantly improved. Early diagnosis and prompt initiation of treatment are critical to patient outcomes.

References

European Association for the Study of the Liver (EASL): Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. Journal of Hepatology, 2018.
Angeli P. et al.: Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. Journal of Hepatology, 2015.
Nadim M.K. et al.: Hepatorenal syndrome. The Lancet, 2012; 379(9819): 1612-1619.

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