Hepatorenal Syndrome: Causes, Symptoms, and Treatment Options

What is hepatorenal syndrome?

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Hepatorenal syndrome (HRS) is a serious and potentially fatal complication that occurs in the context of advanced liver diseases, especially decompensated cirrhosis. It is characterized by acute kidney failure of functional origin, in the absence of structural damage to the kidneys. In other words, although the kidneys are morphologically intact, they suddenly lose their filtering capacity due to circulatory imbalances induced by severe liver damage.

The mechanism of onset involves intense renal vasoconstriction – that is, a significant narrowing of the blood vessels that supply the kidneys – associated with systemic arterial vasodilation, especially in the splanchnic circulation (abdominal area). These changes are supported by the activation of endogenous vasoactive systems, such as the renin-angiotensin-aldosterone system and the sympathetic nervous system, which directly affect blood pressure and renal blood flow.

Types of hepatorenal syndrome:

• HRS type 1 (acute): develops rapidly, within days, with sudden deterioration of kidney function.
• HRS type 2 (chronic): progresses slowly, over weeks or months, and is usually associated with refractory ascites.

Although hepatorenal syndrome has a poor prognosis, rapid therapeutic intervention is essential. The only curative treatment remains liver transplantation. Until the time of transplantation, drug treatments such as systemic vasoconstrictors (e.g., terlipressin) associated with albumin administration can temporarily stabilize kidney function.

As a general observation for supporting liver health, long-term care and maintaining a balanced lifestyle are important. In fact, some dietary supplements specially formulated for liver protection can be integrated into the support regimen. For example, formulas like Premium Hepato-Care, developed locally, can support liver function through natural ingredients tailored to the needs of patients with chronic liver conditions – of course, always upon the recommendation of the treating physician.

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Causes and risk factors associated with hepatorenal syndrome

Hepatorenal syndrome (HRS) is a severe and potentially lethal complication that frequently occurs in the advanced stages of liver cirrhosis. Cirrhosis is a chronic liver disease characterized by progressive fibrosis and impaired normal liver function. HRS does not reflect a primary kidney disease but rather a functional dysfunction of the kidneys, triggered by systemic changes induced by severe liver damage.

The main risk factors for developing HRS are:

• Decompensated liver cirrhosis: This is the most important risk factor. In this stage, the liver can no longer meet the body’s demands, and complications such as ascites and hepatic encephalopathy are frequent. Also, portal hypertension – increased pressure in the portal vein – significantly contributes to the onset of HRS.
• Refractory ascites: Refers to the chronic accumulation of fluid in the peritoneal cavity, resistant to diuretic treatments, favoring circulatory imbalances that can lead to kidney failure.
• Spontaneous bacterial peritonitis (SBP): Is a serious infection of the ascites fluid, which can trigger or worsen HRS.
• Upper gastrointestinal bleeding: Significant blood loss can reduce renal perfusion and trigger the onset of HRS.
• Excessive use of diuretics: Although essential in the treatment of ascites, their administration in high doses can lead to hypovolemia and reduced renal blood flow.
• Large volume paracentesis without albumin replacement: Involves massive evacuation of ascites fluid without albumin supplementation, which can cause circulatory imbalances and accelerate the onset of HRS.
• Severe alcoholic hepatitis: In patients with chronic alcohol consumption and liver damage, acute liver inflammation can precipitate the onset of HRS.

Other predisposing factors:

• Advanced age;
• High Child-Pugh score (classifies cirrhosis severity);
• Hyponatremia (low blood sodium concentration);
• Hyperbilirubinemia (elevated bilirubin levels in the blood);
• Low mean arterial pressure.

Patients with HRS often present with general and non-specific symptoms, such as:

• Severe fatigue;
• Nausea;
• Diffuse abdominal discomfort;
• Metallic or unpleasant taste in the mouth.

Other manifestations

In most cases, these manifestations overlap with the existing symptoms of cirrhosis and liver failure:

• Jaundice (yellowing of the skin and eyes);
• Frequent bleeding or bruising;
• Pale stools and dark urine;
• Ascites (enlarged abdomen due to fluid accumulation);
• Hepatomegaly and splenomegaly (enlarged liver and spleen);
• Cutaneous pruritus (persistent itching);
• Signs of hepatic encephalopathy (confusion, cognitive impairments).

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Diagnosis of hepatorenal syndrome

The diagnosis of hepatorenal syndrome (HRS) is complex and is based on the exclusion of other causes of acute kidney failure in patients with advanced liver disease. To establish the diagnosis, doctors start with essential clinical criteria, followed by detailed paraclinical and imaging tests:

• Presence of decompensated liver cirrhosis and ascites – key elements defining the clinical context.
• Increase in serum creatinine level by ≥0.3 mg/dL within 48 hours or ≥50% from the initial value within 7 days.
• Absence of a significant response to volume expansion with intravenous albumin (1g/kg body weight/day for 2 days).
• No recent episodes of shock or major hemodynamic instability.
• No use of nephrotoxic medications (such as NSAIDs or certain antibiotics) recently.
• No signs of structural kidney damage, such as proteinuria, hematuria, or significant renal ultrasound changes.

In contrast, paraclinical investigations used for confirmation include:

• Serial creatinine and urea tests – for monitoring kidney function.
• Complete urinalysis, to exclude the presence of proteins or blood – suggestive of other kidney diseases.
• Abdominal ultrasound, to check the appearance of the kidneys and the amount of ascites fluid.
• Liver function tests, such as transaminases, bilirubin, INR.
• Determination of urinary sodium, which is often <10 mEq/L in HRS – an indication of renal sodium retention.

It is important to rule out other causes of acute kidney failure, such as:

• Hypovolemia, caused by gastrointestinal bleeding, vomiting, diarrhea, or excessive use of diuretics.
• Septic shock, a major cause of multiple organ failure, including renal.
• Drug nephrotoxicity, common in patients with comorbidities and multiple treatments.
• Primary kidney diseases, such as glomerulonephritis or obstructive nephropathy (e.g., stones, tumor compression).

Treatment of hepatorenal syndrome

Once kidney failure has occurred, hepatorenal syndrome becomes a major medical emergency. The underlying cause remains advanced liver disease, and treatment must primarily aim at restoring liver function.

Kidney dysfunction in HRS is of a “pre-renal” type, meaning that the kidneys are not structurally affected, but their function is compromised by a severe decrease in blood perfusion. If these kidneys were transplanted into a healthy body, they would function normally. Therefore, restoring liver function is essential for renal recovery.

Liver transplantation is often the only definitive therapeutic option, as liver disease has reached an irreversible stage. Unfortunately, not all patients are eligible for transplantation, and resources (available organs) are limited. Access to this procedure is through the national transplant program and involves complex evaluation based on strict criteria.

During the waiting period for transplantation, treatments are applied to maintain kidney function and alleviate symptoms, without being able to cure the disease.

Supportive therapeutic measures are based on:

• Intravenous hydration, to support circulating volume and correct electrolyte imbalances.
• Discontinuation of nephrotoxic medications, especially diuretics or other treatments that may worsen kidney failure.
• Antibiotics, if infection is suspected (e.g., spontaneous bacterial peritonitis).
• Paracentesis, for the evacuation of excess ascites fluid (accompanied by albumin administration to prevent complications).
• Systemic vasoconstrictors (such as terlipressin), which help redirect blood flow to the kidneys.
• Hemodialysis, used in severe cases to temporarily replace kidney function until transplantation.

It is important to understand that these measures have symptomatic and supportive roles, without being able to correct the underlying cause – severe liver dysfunction. However, they can improve the patient’s general condition, contributing to increased survival chances and a more favorable post-transplant outcome.

Prevention and control of hepatorenal syndrome

The most effective method of preventing hepatorenal syndrome is the early and correct control of the underlying liver disease before it progresses to cirrhosis.

Liver damage typically has a slow progression that spans years. Therefore, initiating treatment in the early stages can significantly slow down the progression of chronic hepatitis and fibrosis, thus reducing the risk of severe complications, such as HRS.

Simple lifestyle changes can have a major impact:

• Quitting alcohol consumption;
• Weight loss in cases of obesity or fatty liver disease;
• Adopting a balanced diet and maintaining an active lifestyle.

If a diagnosis of cirrhosis has already been established, preventing HRS becomes more difficult, and its appearance is unpredictable. However, measures can be taken to reduce the risk, particularly by preventing bacterial infections, which are the main triggers of the syndrome:

• Administration of prophylactic antibiotics to high-risk patients (e.g., those with severe ascites);
• Strict adherence to personal and medical hygiene rules, including careful care of catheters and avoidance of unnecessary invasive procedures.

Therefore, HRS prevention is based on two major directions: active and responsible treatment of liver disease from an early stage and avoidance of complications, especially infections, in the advanced stages of cirrhosis.

Prognosis and quality of life for patients diagnosed with hepatorenal syndrome

In the absence of liver transplantation, the prognosis for patients with hepatorenal syndrome is extremely poor. In the acute form, the average survival rate is about 2 weeks from onset. In the chronic form, survival can extend up to 6 months.

The more severe the liver failure, the more unfavorable the prognosis.

For patients who undergo liver transplantation, the prognosis improves considerably. The survival rate is approximately 60% at 3 years after transplantation, and kidney function recovers in most cases within the first few weeks postoperatively.

In conclusion, although the prognosis of HRS remains poor, a prompt and comprehensive therapeutic approach, including medical treatment, management of complications, and psychological support, can improve both survival and quality of life for patients affected by this severe complication of liver cirrhosis. At the same time, it is imperative that patients with HRS are cared for by an experienced medical team and receive the support of family and friends.

This article is for informational purposes only and does not replace professional medical advice. For a correct diagnosis and an appropriate treatment plan, always consult your treating physician!

References:

1. https://www.ncbi.nlm.nih.gov/books/NBK430856/;
2. https://my.clevelandclinic.org/health/diseases/23399-hepatorenal-syndrome;
3. https://www.elsevier.es/en-revista-annals-hepatology-16-articulo-hepatorenal-syndrome-S1665268119321544;
4. https://rarediseases.org/rare-diseases/hepatorenal-syndrome/.