What is the cause of Acute Kidney Injury (AKI) in cirrhosis with hyperammonemia?

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Last updated: May 21, 2025View editorial policy

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From the Guidelines

Acute kidney injury (AKI) in cirrhosis with hyperammonemia is primarily caused by hepatorenal syndrome (HRS), a functional renal impairment that occurs due to severe circulatory dysfunction, as well as other factors such as prerenal azotemia, acute tubular necrosis, and infection-related kidney injury, as supported by the most recent evidence 1.

Causes of AKI in Cirrhosis with Hyperammonemia

The causes of AKI in these patients are multifactorial and include:

  • Hepatorenal syndrome (HRS), characterized by intense renal arteriolar vasoconstriction leading to reduced kidney blood flow and impaired function 1
  • Prerenal azotemia from volume depletion, often due to diuretic use, gastrointestinal bleeding, or lactulose-induced diarrhea
  • Acute tubular necrosis from nephrotoxic medications or contrast agents
  • Infection-related kidney injury, particularly spontaneous bacterial peritonitis
  • Hyperammonemia itself, which can contribute to AKI through direct tubular toxicity and by promoting systemic inflammation

Management of AKI in Cirrhosis with Hyperammonemia

Management should focus on:

  • Identifying and treating the underlying cause of AKI
  • Maintaining adequate volume status
  • Avoiding nephrotoxins
  • Treating infections promptly
  • Considering vasoconstrictors like terlipressin or norepinephrine with albumin for HRS, as recommended in the most recent guidelines 1 Early recognition and intervention are crucial as AKI significantly worsens prognosis in cirrhotic patients.

Key Recommendations

  • Discontinue diuretics and beta-blockers, and avoid nephrotoxic drugs, such as vasodilators or NSAIDs, as recommended by recent guidelines 1
  • Use volume replacement therapy, such as crystalloids or albumin, as needed, and consider therapeutic paracentesis with albumin infusion in patients with tense ascites 1
  • Consider vasoconstrictor therapy, such as terlipressin or norepinephrine, with albumin for patients with HRS, as supported by recent evidence 1

From the Research

Causes of AKI in Cirrhosis with Hyperammonia

  • The exact cause of Acute Kidney Injury (AKI) in cirrhosis with hyperammonia is not explicitly stated in the provided studies, but several factors can contribute to the development of AKI in cirrhotic patients 2.
  • Pre-renal AKI, hepatorenal syndrome type of AKI (HRS-AKI), and acute tubular necrosis are the most common causes of AKI in cirrhosis 2.
  • Hyperammonemia can lead to hepatic encephalopathy, a serious complication of liver cirrhosis, but its direct role in causing AKI is not clearly established in the provided studies 3, 4, 5.

Relationship between Hyperammonia and AKI

  • Elevated ammonia levels are associated with bad prognosis in cirrhosis, but the correlation between ammonemia and the severity of symptoms is individually poor 5.
  • Hyperammonemia can be a factor in the development of hepatic encephalopathy, which may indirectly contribute to the development of AKI in cirrhotic patients 3, 4, 5.
  • Zinc supplementation has been shown to decrease blood ammonia levels in patients with liver cirrhosis and hyperammonemia, which may have a positive effect on reducing the risk of AKI 6.

Diagnostic and Therapeutic Considerations

  • Measuring ammonemia in cirrhotic patients is not recommended systematically, even in the presence of neurological symptoms, due to its low sensitivity and specificity 5.
  • The diagnosis of AKI in cirrhosis requires careful consideration of the underlying causes, and treatment differs substantially depending on the type of AKI 2.
  • Early identification and management of hyperammonemia are crucial to prevent irreversible brain damage and potentially reduce the risk of AKI in cirrhotic patients 3, 4, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Pharmacotherapy for hyperammonemia.

Expert opinion on pharmacotherapy, 2014

Research

Why and when to measure ammonemia in cirrhosis?

Clinics and research in hepatology and gastroenterology, 2018

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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