Hepatorenal syndrome

Overview

Hepatorenal syndrome (HRS) is a serious and potentially life-threatening complication of advanced liver disease, particularly cirrhosis. It is characterized by the rapid deterioration of kidney function in individuals with severe liver dysfunction, in the absence of any underlying kidney disease. HRS is a form of functional renal failure caused by alterations in blood flow and vascular resistance, and not due to structural damage of the kidneys. Prompt diagnosis and treatment are critical, as HRS is associated with a poor prognosis if left untreated.

Causes

Hepatorenal syndrome occurs in patients with advanced liver disease, especially those with cirrhosis and ascites. The condition is driven by severe liver dysfunction that leads to:

• Splanchnic vasodilation: Excessive widening of blood vessels in the abdomen due to nitric oxide and other vasodilators

• Reduced effective blood volume: Despite fluid retention, less blood reaches the kidneys

• Activation of vasoconstrictor systems: Such as the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system, leading to renal vasoconstriction

These hemodynamic changes reduce renal blood flow and glomerular filtration rate, resulting in kidney failure. HRS can be triggered by infections (especially spontaneous bacterial peritonitis), gastrointestinal bleeding, or overuse of diuretics.

Symptoms

Symptoms of hepatorenal syndrome are often nonspecific and may overlap with those of liver failure. Common signs and symptoms include:

• Decreased urine output (oliguria)

• Dark or concentrated urine

• Fatigue and weakness

• Confusion or altered mental status (hepatic encephalopathy)

• Swelling in the abdomen (ascites) and legs (edema)

• Low blood pressure

Symptoms of the underlying liver disease — such as jaundice, easy bruising, and gastrointestinal bleeding — are typically present as well.

Diagnosis

HRS is a diagnosis of exclusion, meaning it is diagnosed after ruling out other causes of acute kidney injury in liver disease. Key diagnostic criteria and evaluations include:

• History and physical exam: Presence of advanced cirrhosis with ascites

• Laboratory tests: Elevated serum creatinine and low urine sodium concentration

• Urinalysis: Typically shows low protein and few abnormalities (indicating functional, not structural damage)

• No improvement with volume expansion: Lack of kidney function improvement after albumin and fluid resuscitation

• Exclusion of other causes: No evidence of shock, nephrotoxic drugs, or intrinsic kidney disease

There are two types of HRS:

• Type 1 HRS: Rapid and progressive renal failure

• Type 2 HRS: More gradual decline, often associated with refractory ascites

Treatment

Treatment of hepatorenal syndrome aims to restore kidney function and address the underlying liver disease. Options include:

• Vasoconstrictor therapy: Medications such as terlipressin (where available), norepinephrine, or midodrine (often combined with octreotide) to improve blood flow to the kidneys

• Albumin infusion: Helps expand blood volume and support kidney perfusion

• Discontinuation of nephrotoxic drugs: Such as NSAIDs or aminoglycosides

• Treatment of precipitating factors: For example, managing infections or gastrointestinal bleeding

• Dialysis: May be used as a temporary measure in critically ill patients

• Liver transplantation: The only definitive cure for HRS; patients should be evaluated urgently for transplant eligibility

Prognosis

The prognosis for hepatorenal syndrome is poor without treatment, particularly for type 1 HRS, which has a median survival of less than two weeks. With medical therapy, kidney function may improve temporarily, but recurrence is common unless liver function is addressed. Liver transplantation offers the best long-term outcome, with many patients experiencing complete reversal of kidney dysfunction post-transplant. Early recognition, supportive care, and referral to a transplant center are essential to improving survival in patients with HRS.