From the Guidelines
Elevated uric acid (hyperuricemia) and hyperammonemia are distinct metabolic abnormalities that require different management approaches. For hyperuricemia, treatment is recommended when levels exceed 7 mg/dL in men or 6 mg/dL in women, or when symptoms like gout or kidney stones occur, as stated in the 2012 American College of Rheumatology guidelines for management of gout 1. First-line medication is allopurinol, starting at 100 mg daily and titrating up to 300-600 mg daily based on uric acid levels and kidney function. Febuxostat (40-80 mg daily) is an alternative for those who cannot tolerate allopurinol. For hyperammonemia, immediate treatment is essential to prevent neurological damage, as emphasized in the consensus guidelines for management of hyperammonaemia in paediatric patients receiving continuous kidney replacement therapy 1. The regimen includes lactulose (20-30 g orally every 6 hours) to reduce intestinal ammonia absorption, rifaximin (550 mg twice daily) to decrease ammonia-producing gut bacteria, and L-ornithine L-aspartate (6-9 g daily) to enhance ammonia metabolism. Protein restriction to 0.6-0.8 g/kg/day is also recommended. In severe cases, hemodialysis may be necessary. These conditions require different approaches because hyperuricemia results from purine metabolism disorders or decreased renal excretion, while hyperammonemia typically stems from liver dysfunction or urea cycle disorders that impair ammonia conversion to urea. Key considerations in managing these conditions include:
- Monitoring uric acid and ammonia levels closely
- Adjusting medication dosages based on kidney function and disease severity
- Implementing dietary restrictions to manage protein intake and reduce ammonia production
- Considering hemodialysis in severe cases of hyperammonemia
- Prioritizing prompt treatment to prevent long-term neurological damage and other complications.
From the FDA Drug Label
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 Allopurinol is an inhibitor of xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine and of xanthine to uric acid, the end product of purine metabolism in man.
The FDA-approved drugs sodium phenylacetate 2 and allopurinol 3 can be used to treat hyperammonemia and elevated uric acid levels, respectively.
- Sodium phenylacetate works by providing an alternative pathway for nitrogen disposal in patients with urea cycle disorders, thereby reducing ammonia levels.
- Allopurinol inhibits xanthine oxidase, reducing uric acid production and lowering serum uric acid levels. However, there is no direct information in the provided drug labels about the combined use of these drugs for treating both conditions simultaneously.
From the Research
Elevated Uric Acid and Hyperammonemia
- Elevated uric acid, also known as hyperuricemia, is a common condition in patients with chronic kidney disease (CKD) 4
- Hyperammonemia, on the other hand, is a condition characterized by elevated levels of ammonia in the blood, which can be caused by various factors, including urea cycle disorders (UCDs) 5, 6, 7, 8
Treatment of Hyperammonemia
- L-carnitine (LC) is commonly used in the treatment of valproate-induced hyperammonemia (VIHA) 5
- Sodium benzoate (SB) and phenylacetate (PA) are also used to reduce hyperammonemia, with PA showing a better therapeutic effect in comparison with SB 5
- Intravenous sodium benzoate has been shown to be an effective and safe treatment for acute episodes of UCDs 6
- The use of combined sodium benzoate and sodium phenylacetate (SBSP) has been implemented in some pediatric intensive care units to treat acute hyperammonemia 7
Relationship between Uric Acid and Hyperammonemia
- There is no direct relationship between elevated uric acid and hyperammonemia, as they are two distinct conditions with different causes and treatments 4
- However, patients with CKD may be at risk of developing hyperammonemia due to impaired renal function, which can lead to the accumulation of ammonia in the blood 4