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In Reply: Dr Waugh raises the potential role of citrulline supplementation as a mechanism to increase arginine levels. A carefully designed trial to compare the efficacy of oral arginine vs citrulline may be worthwhile, particularly in children. However, citrulline levels are generally higher in adult patients with pulmonary hypertension and correlate with rising creatinine levels,¹ suggesting impaired ability of kidneys to convert citrulline to arginine. Although we found that the ratio of arginine to ornithine was an excellent biomarker of arginase activity in this patient population and correlated with severity of pulmonary hypertension and mortality, including citrulline in the denominator of this ratio (arginine/[ornithine + citrulline]) identified a group of patients at even greater risk of early death. Therefore, patients with renal dysfunction and secondary accumulation of citrulline may require special consideration, as chronic end-organ damage to the kidney is common in patients with SCD and pulmonary hypertension and is associated with . . . [Full Text of this Article]

Claudia R. Morris, MD
claudiamorris@comcast.net
Department of Emergency Medicine

Elliott P. Vichinsky, MD
Department of Hematology-Oncology
Children’s Hospital and Research Center at Oakland
Oakland, Calif

Gregory J. Kato, MD; Mark T. Gladwin, MD
Vascular Therapeutics Section, Cardiovascular Branch
National Heart, Lung, and Blood Institute
Bethesda, Md

Stanley Hazen, MD, PhD
Center for Cardiovascular Diagnostics and Prevention
Cleveland Clinic Foundation
Cleveland, Ohio

Sidney M. Morris, Jr, PhD
Department of Molecular Genetics and Biochemistry
University of Pittsburgh School of Medicine
Pittsburgh, Pa

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