Blood Ammonia and Glutamine as Predictors of Hyperammonemic Crises in Urea Cycle Disorder Patients
نویسندگان
چکیده
Purpose—To examine predictors of ammonia exposure and hyperammonemic crises (HAC) in patients with urea cycle disorders (UCDs). Methods—The relationships between fasting ammonia, daily ammonia exposure, and HACs were analyzed in >100 UCD patients. Results—Fasting ammonia correlated strongly with daily ammonia exposure (r=0.764, p<0.001). For patients with fasting ammonia levels <0.5 ULN, 0.5 to <1.0 ULN, and ≥1.0 ULN, the probability of a normal average daily ammonia value was 87%, 60%, and 39%, respectively, and 10.3%, 14.1%, and 37.0% of these patients experienced ≥1 HAC over 12 months. Time to first HAC was shorter (p=0.008) and relative risk (4.5×; p=0.011) and rate (~5×, p=0.006) of HACs higher in patients with fasting ammonia ≥1.0 ULN vs. <0.5ULN; relative risk was even greater (20×; p=0.009) in patients ≥6 years. A 10 or 25 μmol/L increase in ammonia exposure increased the relative risk of a HAC by 50% and >200% (p<0.0001), respectively. The relationship between ammonia and HAC risk appeared independent of treatment, age, UCD subtype, dietary protein intake, or blood urea nitrogen. Fasting glutamine correlated weakly with AUC0-24 and was not a significant predictor of HACs. Conclusions—Fasting ammonia correlates strongly and positively with daily ammonia exposure and with the risk and rate of HACs, suggesting that UCD patients may benefit from tight ammonia control.
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