From the Guidelines
Arginine supplementation is crucial in pediatric patients with urea cycle disorders, and the recommended dose is 200 mg/kg in patients with ornithine transcarbamylase and carbamoyl phosphate synthase I deficiencies, and 600 mg/kg in patients with argininosuccinate synthase and argininosuccinate lyase deficiencies, as stated in the 2020 consensus guidelines for management of hyperammonaemia in pediatric patients receiving continuous kidney replacement therapy 1.
Key Considerations
- The dose of arginine supplementation varies based on the specific urea cycle disorder and the patient's weight.
- Arginine plays a critical role in the urea cycle, helping to remove ammonia from the body.
- It is also a precursor for nitric oxide, which improves blood flow, and is involved in protein synthesis and growth hormone secretion.
Administration and Monitoring
- Arginine supplementation should be administered intravenously over 90 minutes as a bolus, followed by maintenance over 24 hours.
- The patient's ammonia levels and clinical status should be closely monitored during treatment.
- In cases of severe encephalopathy and/or seizure, treatment with ammonia-scavenging agents, including arginine, should be initiated promptly.
Additional Recommendations
- The 2018 ESPGHAN/ESPE/ESPR/CSPEN guidelines on pediatric parenteral nutrition recommend that arginine supplementation may be used for prevention of necrotizing enterocolitis in preterm infants 1.
- The 2014 practice guideline by the American Association for the Study of Liver Diseases, American Society of Transplantation, and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition notes that children receiving a liver transplant for arginosuccinic aciduria may still require arginine supplementation during periods of physiological stress or fasting due to persistent deficiency in extrahepatic tissues 1.
From the Research
Arginine in Paediatrics
- Arginine is a conditionally essential amino acid that plays a critical role in ammonia detoxification, and nitric oxide and creatine production 2.
- Arginine supplementation has been proposed and trialled in several disorders, including vascular diseases and asthma, mitochondrial encephalopathy lactic acidosis and stroke-like episodes (MELAS), glutaric aciduria type I and disorders of creatine metabolism, both production and transportation into the central nervous system 2.
- L-citrulline, a natural precursor of L-arginine, is more bioavailable than L-arginine and has a longer circulation time, making it a potential therapeutic option for improving endogenous nitric oxide regulation in cardiovascular diseases associated with endothelial dysfunction 3.
Therapeutic Potential of Arginine in Children
- Arginine/citrulline has immense therapeutic potential in some life-threatening diseases in children, but the optimal clinical development of arginine or citrulline in children requires more information about pharmacokinetics and exposure-response relationships at appropriate ages and under relevant disease states 3.
- Oral arginine supplementation has been shown to improve cardiopulmonary hemodynamics during sickle cell disease vasoocclusive pain and acute chest syndrome (ACS) in children 4.
- Polymorphisms in urea cycle enzyme genes, such as carbamoyl phosphate synthase 1 gene (CPS1), have been associated with persistent pulmonary hypertension of the newborn (PPHN), suggesting a potential link between arginine metabolism and PPHN 5.
Urea Cycle Disorders and Arginine
- The urea cycle is a metabolic pathway for the disposal of excess nitrogen, and congenital defects of the enzymes or transporters of the urea cycle can cause urea cycle disorders (UCDs) 6.
- Arginine supplementation is an essential component for the treatment of UCDs, but the optimal dosing and treatment strategies are still being researched 2, 6.