Hyperammonemia in Urea Cycle Disorders: Role of the Nephrologist

Abstract

Severe hyperammoniemia denotes a clinical condition associated with high blood ammonia levels and uncertain prognosis. The presentation can vary with the age of the patient and the magnitude of the increase in blood ammonia levels. Persistent hyperammonemia, if not treated rapidly, may cause irreversible neuronal damage. The aim of therapy should be to normalize blood ammonia levels. Recent experience has provided treatment guidelines that include minimizing endogenous ammonia production and protein catabolism, restricting nitrogen intake, administering substrates of the urea cycle, administering compounds that facilitate the removal of ammonia through alternative pathways, and, in severe cases, dialysis therapy. Hemodialysis is the most effective treatment for rapidly reducing blood ammonia levels. Continuous hemofiltration and peritoneal dialysis are also effective modalities to reduce blood ammonia levels. An improved understanding of the metabolism of ammonia and clinical consequences of hyperammonemia will assist the nephrologist in providing optimal care for this high-risk patient population.