Low Arginine Bioavailability and Clinical Outcomes in Children with Sickle Cell Disease Hospitalized with Vaso-Occlusive Pain Episode

Introduction: Global arginine bioavailability ratio (GABR) (Arginine/[Citrulline+Ornithine]) is associated with clinical outcomes including pain, pulmonary hypertension, and mortality in patients with sickle cell disease (SCD). Arginine replacement therapy has demonstrated opioid-sparing effects, improved blood pressure and cardiovascular function, and shorten length of hospital stay. Arginine is a conditionally essential amino acid synthesized from citrulline in the kidneys. During a vaso-occlusive pain episode (VOE), hemolysis leads to the release of erythrocyte-arginase (arginine-metabolizing enzyme) that metabolizes arginine into ornithine. Arginine-to-ornithine ratio (arg/orn) is a biomarker of arginase activity and GABR incorporates the impact of kidney function on global arginine bioavailability. The association between arginine bioavailability and clinical outcomes has not been sufficiently explored in children with SCD-VOE.