Clinical Study to Evaluate the Possible Efficacy and Safety of -Arginine in Children with Sickle Cell Disease and Increased Tricuspid Regurgitant Jet Velocity: a Randomized Controlled Trial

Quinn CT. Minireview: Clinical severity in sickle cell disease: the challenges of definition and prognostication. Exp Biol Med. 2016;241:679–88.

Article  CAS  Google Scholar 

Hassan T, Badr M, Hanna D, Arafa M, Elhewala A, Dabour S, et al. Retinopathy in Egyptian patients with sickle cell disease: a cross-sectional study. Med (United States). 2021;100(51): e28355.

CAS  Google Scholar 

Al Kahf S, Roche A, Baron A, Chantalat-Auger C, Savale L. Pulmonary hypertension in sickle cell disease. Press Medicale. 2023;52(4): 104209.

Article  Google Scholar 

Mehari A, Alam S, Tian X, Cuttica MJ, Barnett CF, Miles G, et al. Hemodynamic predictors of mortality in adults with sickle cell disease. Am J Respir Crit Care Med. 2013;187:840–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gladwin MT, Sachdev V, Jison ML, Shizukuda Y, Plehn JF, Minter K, et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004;350:886–95.

Article  CAS  PubMed  Google Scholar 

Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62:D34-41.

Article  PubMed  Google Scholar 

Shilo NR, Morris CR. Pathways to pulmonary hypertension in sickle cell disease: the search for prevention and early intervention. Expert Rev Hematol. 2017;10:875–90.

Article  CAS  PubMed  Google Scholar 

Machado RF, Anthi A, Steinberg MH, Bonds D, Sachdev V, Kato GJ, et al. N-terminal pro-brain natriuretic peptide levels and risk of death in sickle cell disease. JAMA. 2006;296:310–8.

Article  CAS  PubMed  Google Scholar 

Potoka KP, Gladwin MT. Vasculopathy and pulmonary hypertension in sickle cell disease. Am J Physiol Lung Cell Mol Physiol. 2015;308:L314–24.

Article  CAS  PubMed  Google Scholar 

Morris CR. Mechanisms of vasculopathy in sickle cell disease and thalassemia. Hematol Am Soc Hematol Educ Progr. 2008;2008(1):177–85.

Tousoulis D, Georgakis MK, Oikonomou E, Papageorgiou N, Zaromitidou M, Latsios G, et al. Asymmetric dimethylarginine: clinical significance and novel therapeutic approaches. Curr Med Chem. 2015;22:2871–901.

Kato GJ, Wang Z, MacHado RF, Blackwelder WC, Taylor VIJG, Hazen SL. Endogenous nitric oxide synthase inhibitors in sickle cell disease: abnormal levels and correlations with pulmonary hypertension, desaturation, haemolysis, organ dysfunction and death. Br J Haematol. 2009;145:506–13.

Article  CAS  PubMed  Google Scholar 

Arigliani M, Gupta A. Management of chronic respiratory complications in children and adolescents with sickle cell disease. Eur Respir Rev. 2020;29:1–9.

Article  Google Scholar 

Wu G, Meininger CJ, McNeal CJ, Bazer FW, Rhoads JM. Role of L-arginine in nitric oxide synthesis and health in humans. Adv Exp Med Biol. 2021;1332:167–87.

Rh B. The pharmacodynamics of L-arginine. Altern Ther Health Med. 2014;20:48–54.

Google Scholar 

Jaja SI, Ogungbemi SO, Kehinde MO, Anigbogu CN. Supplementation with L-arginine stabilizes plasma arginine and nitric oxide metabolites, suppresses elevated liver enzymes and peroxidation in sickle cell anaemia. Pathophysiology. 2016;23:81–5.

Article  CAS  PubMed  Google Scholar 

King DE, Mainous AG, Geesey ME. Variation in L-arginine intake follow demographics and lifestyle factors that may impact cardiovascular disease risk. Nutr Res. 2008;28:21–4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Picard MH, Adams D, Bierig SM, Dent JM, Douglas PS, Gillam LD, et al. American Society of Echocardiography recommendations for quality echocardiography laboratory operations. J Am Soc Echocardiogr. 2011;24:1–10.

Article  PubMed  Google Scholar 

Lai WW, Geva T, Shirali GS, Frommelt PC, Humes RA, Brook MM, et al. Guidelines and standards for performance of a pediatric echocardiogram: a report from the Task Force of the Pediatric Council of the American Society of Echocardiography. 2006;19(12):1413–30.

Google Scholar 

Little JA, Hauser KP, Martyr SE, Harris A, Maric I, Morris CR, et al. Hematologic, biochemical, and cardiopulmonary effects of L-arginine supplementation or phosphodiesterase 5 inhibition in patients with sickle cell disease who are on hydroxyurea therapy. Eur J Haematol. 2009;82(4):315–21.

Article  CAS  PubMed  Google Scholar 

Pavan AR, Terroni B, Dos Santos JL. Endothelial dysfunction in Sickle Cell Disease: strategies for the treatment. Nitric Oxide - Biol Chem. 2024;149:7–17.

Article  CAS  Google Scholar 

Gladwin MT, Barst RJ, Gibbs JSR, Hildesheim M, Sachdev V, Nouraie M, et al. Risk factors for death in 632 patients with sickle cell disease in the United States and United Kingdom. PLoS ONE. 2014;9(7): e99489.

Article  PubMed  PubMed Central  Google Scholar 

Mehari A, Gladwin MT, Tian X, Machado RF, Kato GJ. Mortality in adults with sickle cell disease and pulmonary hypertension. JAMA. 2012;307:1254–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Morris CR, Morris SM, Hagar W, Van Warmerdam J, Claster S, Kepka-Lenhart D, et al. Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease? Am J Respir Crit Care Med. 2003;168:63–9.

Article  PubMed  Google Scholar 

Onalo R, Cilliers A, Cooper P, Morris CR. Arginine therapy and cardiopulmonary hemodynamics in hospitalized children with sickle cell anemia: a prospective, double-blinded, randomized placebo-controlled clinical trial. Am J Respir Crit Care Med. 2022;206:70–80.

Article  CAS  PubMed  PubMed Central  Google Scholar 

El-Khateeb E, El-Haggar SM, El-Razaky O, El-Shanshory MR, Mostafa TM. Randomized clinical and biochemical study comparing the effect of L-arginine and sildenafil in beta thalassemia major children with high tricuspid regurgitant jet velocity. J Cardiovasc Pharmacol Ther. 2022;27:10742484221132672.

Article  CAS  PubMed  Google Scholar 

Ten Kate CA, Tibboel D, Kraemer US. B-type natriuretic peptide as a parameter for pulmonary hypertension in children. A systematic review Eur J Pediatr. 2015;174:1267–75.

Article  PubMed  Google Scholar 

Voskaridou E, Tsetsos G, Tsoutsias A, Spyropoulou E, Christoulas D, Terpos E. Pulmonary hypertension in patients with sickle cell/beta thalassemia: incidence and correlation with serum N-terminal pro-brain natriuretic peptide concentrations. Haematologica. 2007;92:738–43.

Article  CAS  PubMed  Google Scholar 

Nouraie M, Barst RJ, Rosenzweig EB, Sachdev V, Machado RF, Hassell K, et al. NT-Probnp as a marker of cardiopulmonary compromise and exercise limitation in adults with sickle cell anemia in the Walk-PHaSST study. Blood. 2010;116:1639.

Article  Google Scholar 

Machado RF, Hildesheim M, Mendelsohn L, Remaley AT, Kato GJ, Gladwin MT. NT-pro brain natriuretic peptide levels and the risk of death in the cooperative study of sickle cell disease. Br J Haematol. 2011;154:512–20.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Morris CR. Alterations of the arginine metabolome in sickle cell disease: a growing rationale for arginine therapy. Hematol Oncol Clin North Am. 2014;28:301–21.

Article  PubMed  Google Scholar 

Morris CR, Kato GJ, Poljakovic M, Wang X, Blackwelder WC, Sachdev V, et al. Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease. JAMA. 2005;294:81–90.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Marealle AI, Siervo M, Wassel S, Bluck L, Prentice AM, Minzi O, et al. A pilot study of a non-invasive oral nitrate stable isotopic method suggests that arginine and citrulline supplementation increases whole-body NO production in Tanzanian children with sickle cell disease. Nitric oxide Biol Chem. 2018;74:19–22.

Article  CAS  Google Scholar 

Walford G, Loscalzo J. Nitric oxide in vascular biology. J Thromb Haemost. 2003;1:2112–8.

Article  CAS  PubMed  Google Scholar 

Van Der Land V, Peters M, Biemond BJ, Heijboer H, Harteveld CL, Fijnvandraat K. Markers of endothelial dysfunction differ between subphenotypes in children with sickle cell disease. Thromb Res. 2013;132:712–7.

Article  PubMed  Google Scholar 

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