From the FDA Drug Label
Urea cycle disorders can result from decreased activity of any of the following enzymes: N-acetylglutamate synthetase (NAGS), carbamyl phosphate synthetase (CPS), argininosuccinate synthetase (ASS), ornithine transcarbamylase (OTC), argininosuccinate lyase (ASL), or arginase (ARG) The causes of hyperammonemia in End-Stage Renal Disease (ESRD) are not directly addressed in the provided drug label. However, the label does mention that urea cycle disorders can result from decreased activity of certain enzymes, which can lead to hyperammonemia.
- Key enzymes involved in urea cycle disorders include:
- N-acetylglutamate synthetase (NAGS)
- Carbamyl phosphate synthetase (CPS)
- Argininosuccinate synthetase (ASS)
- Ornithine transcarbamylase (OTC)
- Argininosuccinate lyase (ASL)
- Arginase (ARG) In patients with hyperammonemia due to deficiencies in enzymes of the urea cycle, Sodium Phenylacetate and Sodium Benzoate Injection has been shown to decrease elevated plasma ammonia levels 1.
From the Research
Hyperammonemia in end-stage renal disease (ESRD) is primarily caused by impaired kidney function leading to decreased ammonia excretion, and management includes limiting dietary protein intake, optimizing dialysis regimens, and administering lactulose or rifaximin as needed. In ESRD patients, several mechanisms contribute to elevated ammonia levels, including reduced renal clearance, uremia-induced alterations in gut microbiota, metabolic acidosis, protein catabolism during dialysis, and certain medications like valproic acid 2. The prevalence of asymptomatic hyperammonemia is higher than symptomatic hyperammonemia, and various risk factors have been identified, including concomitant medications, liver injury, and defects in carnitine metabolism 2.
Some key points to consider in the management of hyperammonemia in ESRD patients include:
- Limiting dietary protein intake to 0.6-0.8 g/kg/day to reduce ammonia production
- Optimizing dialysis regimens to improve ammonia removal
- Treating underlying infections that may increase protein catabolism
- Administering lactulose (15-30 ml orally 2-4 times daily) to reduce intestinal ammonia absorption
- Considering rifaximin (550 mg twice daily) to decrease ammonia-producing gut bacteria
- Monitoring ammonia levels, especially in patients taking valproic acid or with a history of liver disease or urea cycle disorders 3
It is essential to recognize and treat hyperammonemia promptly, as it can lead to neurological complications, including encephalopathy, which presents as confusion, lethargy, and potentially coma in severe cases. In some cases, carnitine supplementation may be useful for reversal of hyperammonemia, allowing patients to continue valproic acid for seizure control 4. However, the decision to initiate treatment should be made on a case-by-case basis, considering the individual patient's risk factors and medical history.