Hyperuricemia in Children and Adolescents: Present Knowledge and Future Directions

Masaru Kubota, Masaru Kubota

Abstract

Recent evidence suggests that hyperuricemia is an important condition in children and adolescents, particularly in association with noncommunicable diseases. This review aims to summarize our current understanding of this condition in pediatric patients. An analysis of serum uric acid reference values in a healthy population indicates that they increase gradually with age until adolescence, with differences between the sexes arising at about 12 years of age. This information should be taken into consideration when defining hyperuricemia in studies. Gout is extremely rare in children and adolescents, and most patients with gout have an underlying disease. The major causes of hyperuricemia are chronic conditions, including Down syndrome, metabolic or genetic disease, and congenital heart disease, and acute conditions, including gastroenteritis, bronchial asthma (hypoxia), malignant disorders, and drug side effects. The mechanisms underlying the associations between these diseases and hyperuricemia are discussed, together with recent genetic information. Obesity is a major cause of hyperuricemia in otherwise healthy children and adolescents. Obesity is often accompanied by metabolic syndrome; hyperuricemia in obese children and adolescents is associated with the components of metabolic syndrome and noncommunicable diseases, including hypertension, insulin resistance, dyslipidemia, and chronic kidney disease. Finally, strategies for the treatment of hyperuricemia, including lifestyle intervention and drug administration, are presented.

References

    1. Wilcox W. D. Abnormal serum uric acid levels in children. Journal of Pediatrics. 1996;128(6):731–741. doi: 10.1016/s0022-3476(96)70322-0.
    1. Yamanaka H. Gout and hyperuricemia in young people. Current Opinion in Rheumatology. 2011;23(2):156–160. doi: 10.1097/bor.0b013e3283432d35.
    1. Neogi T. Gout. New England Journal of Medicine. 2011;364(5):443–452. doi: 10.1056/nejmcp1001124.
    1. Yamanaka H., Japanese Society of Gout and Nucleic Acid Metabolism Japanese guideline for the management of hyperuricemia and gout: second edition. Nucleosides, Nucleotides Nucleic Acids. 2011;30(12):1018–1029. doi: 10.1080/15257770.2011.596496.
    1. Clifford S. M., Bunker A. M., Jacobsen J. R., Roberts W. L. Age and gender specific pediatric reference intervals for aldolase, amylase, ceruloplasmin, creatine kinase, pancreatic amylase, prealbumin, and uric acid. Clinica Chimica Acta. 2011;412(9-10):788–790. doi: 10.1016/j.cca.2011.01.011.
    1. Kubota M., Nagai A., Tang L., Tokuda M. Investigation on hyperuricemia in children with obesity or various pediatric disorders. Nucleosides, Nucleotides and Nucleic Acids. 2011;30(12):1051–1059. doi: 10.1080/15257770.2011.597370.
    1. Loh T. P., Metz M. P. Trends and physiology of common serum biochemistries in children aged 0–18 years. Pathology. 2015;47(5):452–461. doi: 10.1097/pat.0000000000000274.
    1. Mikuls T. R., Farrar J. T., Bilker W. B., Fernandes S., Schumacher H. R., Jr., Saag K. G. Gout epidemiology: results from the UK general practice research database, 1990–1999. Annals of the Rheumatic Diseases. 2005;64(2):267–272. doi: 10.1136/ard.2004.024091.
    1. Kim J.-W., Kwak S. G., Lee H., Kim S.-K., Choe J.-Y., Park S.-H. Prevalence and incidence of gout in Korea: data from the national health claims database 2007–2015. Rheumatology International. 2017;37(9):1499–1506. doi: 10.1007/s00296-017-3768-4.
    1. Kato R., Kubota M., Higashiyama Y., Nagai A. A nationwide epidemiological study of gout in childhood and adolescence. Gout and Nucleic Acid Metabolism. 2014;38(1):43–48. doi: 10.6032/gnam.38.43. in Japanese.
    1. Ciompi M. L., Bazzichi L. M., Bertolucci D., et al. Uric acid metabolism in two patients with coexistent Down’s syndrome and gout. Clinical Rheumatology. 1984;3(2):229–233. doi: 10.1007/bf02030760.
    1. Zhang W., Bao C.-d., Gu Y.-y., Ye S. Glycogen storage disease manifested as gout and myopathy: three case reports and literature review. Clinical Rheumatology. 2008;27(5):671–674. doi: 10.1007/s10067-007-0798-4.
    1. Trück J., Laube G. F., von Vigier R. O., Goetschel P. Gout in pediatric renal transplant recipients. Pediatric Nephrology. 2010;25(12):2535–2538. doi: 10.1007/s00467-010-1599-6.
    1. Morley C. J., Houston I. B., Morris-Jones P. Acute renal failure and gout as presenting features of acute lymphoblastic leukaemia. Archives of Disease in Childhood. 1976;51(9):723–725. doi: 10.1136/adc.51.9.723.
    1. Charuvanij S., Pattaragarn A., Wisuthsarewong W., Vatanavicharn N. Juvenile gout in methylmalonic acidemia. Pediatrics International. 2016;58(6):501–503. doi: 10.1111/ped.12857.
    1. Cameron J. S., Moro F., Simmonds H. A. Gout, uric acid and purine metabolism in paediatric nephrology. Pediatric Nephrology. 1993;7(1):105–118. doi: 10.1007/bf00861588.
    1. Nyhan W. L. Inherited Hyperuricemic Disorders. Vol. 147. Contributions to Nephrology; 2005.
    1. Fuller R. W., Luce M. W., Mertz E. T. Serum uric acid in mongolism. Science. 1962;137(3533):868–869. doi: 10.1126/science.137.3533.868.
    1. Málaga S., Pardo R., Málaga I., Orejas G., Fernández-Toral J. Renal involvement in Down syndrome. Pediatric Nephrology. 2005;20(5):614–617. doi: 10.1007/s00467-005-1825-9.
    1. Kashima A., Higashiyama Y., Kubota M., Kawaguchi C., Takahashi Y., Nishikubo T. Children with Down’s syndrome display high rates of hyperuricaemia. Acta Paediatrica. 2014;103(8):e359–e364. doi: 10.1111/apa.12664.
    1. Puukka R., Puukka M., Perkkila L., Kouvalainen K. Levels of some purine metabolizing enzymes in lymphocytes from patients with Down’s syndrome. Biochemical Medicine and Metabolic Biology. 1986;36(1):45–50. doi: 10.1016/0885-4505(86)90105-2.
    1. Gartlet T. R., Parisotto E. B., de Medeiros Gda S., et al. Systemic oxidative stress in children and teenagers with Down syndrome. Life Sciences. 2013;93(16):558–563. doi: 10.1016/j.lfs.2013.08.017.
    1. Martínez-Quintana E., Rodríguez-González F. Hyperuricaemia in congenital heart disease patients. Cardiology in the Young. 2015;25(1):29–34. doi: 10.1017/s1047951113001443.
    1. Rodríguez-Hemández J. L., Rodríguez-González F., Riaño-Ruiz M., Martínez-Quintana E. Risk factors for hyperuricemia in congenital heart disease patients and its relation to cardiovascular death. Congenital Heart Disease. 2018;13(5):655–662. doi: 10.1111/chd.12620.
    1. Cameron J. S., Simmonds H. A. Hereditary hyperuricemia and renal disease. Seminars in Nephrology. 2005;25(1):9–18. doi: 10.1016/j.semnephrol.2004.09.003.
    1. Hart T. C., Gorry M. C., Hart P. S., et al. Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy. Journal of Medical Genetics. 2002;39(12):882–892. doi: 10.1136/jmg.39.12.882.
    1. Matsuo H., Yamamoto K., Nakaoka H., et al. Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes. Annals of the Rheumatic Diseases. 2016;75(4):652–659. doi: 10.1136/annrheumdis-2014-206191.
    1. Wu J., Qiu L., Guo X. Z., et al. Apolipoprotein E gene polymorphisms are associated with primary hyperuricemia in a Chinese population. PLoS One. 2014;9(10) doi: 10.1371/journal.pone.0110864.e110864
    1. Kovacs A., Chan L., Hotrakitya C., Overturf G., Portnoy B. Rotavirus gastroenteritis. American Journal of Diseases of Children. 1987;141(2):161–166. doi: 10.1001/archpedi.1987.04460020051025.
    1. Palumbo E., Branchi M., Malorgio C., Siani A., Bonora G. Diarrhea in children: etiology and clinical aspects. Minerva pediatrica. 2010;62(4):347–351.
    1. Matsuo H., Tsunoda T., Ooyama K., et al. Hyperuricemia in acute gastroenteritis is caused by decreased urate excretion via ABCG2. Scientific Reports. 2016;6(1):p. 31003. doi: 10.1038/srep31003.
    1. Abdulnaby N. K., Sayed A. O., Shalaby N. M. Predictive value of serum uric acid in hospitalized adolescents and adults with acute asthma. Therapeutics and Clinical Risk Management. 2016;12:1701–1708. doi: 10.2147/tcrm.s116188.
    1. Verhulst S. L., Van Hoeck K., Schrauwen N., et al. Sleep-disordered breathing and uric acid in overweight and obese children and adolescents. Chest. 2007;132(1):76–80. doi: 10.1378/chest.06-2930.
    1. Jones D. P., Stapleton F. B., Kalwinsky D., McKay C. P., Kellie S. J., Pui C.-H. Renal dysfunction and hyperuricemia at presentation and relapse of acute lymphoblastic leukemia. Medical and Pediatric Oncology. 1990;18(4):283–286. doi: 10.1002/mpo.2950180405.
    1. Nagai A., Kubota M., Tang L., Adachi S., Usami I., Matsubara K. Hyperuricemia in pediatric malignancies before treatment. Nucleosides, Nucleotides and Nucleic Acids. 2011;30(12):1060–1065. doi: 10.1080/15257770.2011.591745.
    1. Galardy P. J., Hochberg J., Perkins S. L., Harrison L., Goldman S., Cairo M. S. Rasburicase in the prevention of laboratory/clinical tumour lysis syndrome in children with advanced mature B-NHL: a children’s oncology group report. British Journal of Haematology. 2013;163(3):365–372. doi: 10.1111/bjh.12542.
    1. Kaplan B. S., Thomson P. D. Hyperuricemia in the hemolytic-uremic syndrome. Archives of Pediatrics & Adolescent Medicine. 1976;130(8):854–856. doi: 10.1001/archpedi.1976.02120090064011.
    1. Diamond H. S., Meisel A. D., Holden D. The natural history of urate overproduction in sickle cell anemia. Annals of Internal Medicine. 1979;90(5):752–757. doi: 10.7326/0003-4819-90-5-752.
    1. Shimizu T., Morikawa A., Maeda S., Mochizuki H., Tokuyama K., Kuroume T. Effect of theophylline on serum uric acid levels in children with asthma. Journal of Asthma. 1994;31(5):387–391. doi: 10.3109/02770909409061318.
    1. Ring H. A., Heller A. J., Marshall W. J., Johnson A. L., Reynolds E. H. Plasma uric acid in patients receiving anticonvulsant monotherapy. Epilepsy Research. 1991;8(3):241–244. doi: 10.1016/0920-1211(91)90070-v.
    1. Şişmanlar T., Aslan A. T., Budakoğlu I. Is hyperuricemia overlooked when treating pediatric tuberculosis patients with pyrazinamide? Journal of Tropical Pediatrics. 2015;61(5):351–356. doi: 10.1093/tropej/fmv042.
    1. Yamamoto T., Moriwaki Y., Suda M., Takahashi S., Hiroishi K., Higashino K. Theophylline-induced increase in plasma uric acid—purine catabolism increased by theophylline. International Journal of Clinical Pharmacology, Therapy, and Toxicology. 1991;29(7):257–261.
    1. Wang Y., Lim H. The global childhood obesity epidemic and the association between socio-economic status and childhood obesity. International Review of Psychiatry. 2012;24(3):176–188. doi: 10.3109/09540261.2012.688195.
    1. Kubota M., Nagai A. Recent Advances in Obesity in Children (Chapter 2) Hyderabad, India: Avid Science; 2015. Factors associated with childhood obesity in Asian countries: a review of recent literature.
    1. Ford E. S., Li C., Cook S., Choi H. K. Serum concentrations of uric acid and the metabolic syndrome among US children and adolescents. Circulation. 2007;115(19):2526–2532. doi: 10.1161/circulationaha.106.657627.
    1. Lee M. S., Wahlqvist M. L., Yu H. L., Pan W. H. Hyperuricemia and metabolic syndrome in Taiwanese children. Asia Pacific Journal of Clinical Nutrition. 2007;16(2):594–600.
    1. Shatat I. F., Abdallah R. T., Sas D. J., Hailpern S. M. Serum uric acid in US adolescents: distribution and relationship to demographic characteristics and cardiovascular risk factors. Pediatric Research. 2012;72(1):95–100. doi: 10.1038/pr.2012.47.
    1. Kawasaki Y., Hosoya M., Yasumura S., et al. The basic data for residents aged 15 years or younger who received a comprehensive health check in 2011-2012 as a part of the fukushima health management survey after the great east Japan earthquake. Fukushima Journal of Medical Science. 2015;61(2):101–110. doi: 10.5387/fms.2015-13.
    1. Li N., Zhang S., Li W., et al. Prevalence of hyperuricemia and its related risk factors among preschool children from China. Scientific Reports. 2017;7(1):p. 9448. doi: 10.1038/s41598-017-10120-8.
    1. Tang L., Kubota M., Nagai A., Mamemoto K., Tokuda M. Hyperuricemia in obese children and adolescents: the relationship with metabolic syndrome. Pediatric Reports. 2010;2(1):p. e12. doi: 10.4081/pr.2010.e12.
    1. Modino S. C., De armas M. G., Mejías S. M., et al. Hyperuricemia and metabolic syndrome in children with overweight and obesity. Endocrinología y Nutrición. 2012;59(7):533–538. doi: 10.1016/j.endonu.2012.06.010.
    1. Cardoso A. S., Gonzaga N. C., Medeiros C. C. M., de Carvalho D. F. Association of uric acid levels with components of metabolic syndrome and non-alcoholic fatty liver disease in overweight or obese children and adolescents. Jornal de Pediatria (Versão em Português) 2013;89(4):412–418. doi: 10.1016/j.jpedp.2012.12.011.
    1. Ságodi L., Fehér V., Kiss-Tóth E., Almási A., Barkai L. Az elhízás anyagcsere-szövődményei serdülőkorban, különös tekintettel az emelkedett húgysavszintek előfordulására. Orvosi Hetilap. 2015;156(22):888–895. doi: 10.1556/650.2015.30140.
    1. Gil-Campos M., Aguilera C. M., Gil C. A. Uric acid is associated with features of insulin resistance syndrome in obese children at prepubertal stage. Nutricion Hospitalaria. 2009;24(5):607–613.
    1. Krzystek-Korpacka M., Patryn E., Kustrzeba-Wojcicka I., Chrzanowska J., Gamian A., Noczynska A. Gender-specific association of serum uric acid with metabolic syndrome and its components in juvenile obesity. Clinical Chemistry and Laboratory Medicine. 2011;49(1):129–136. doi: 10.1515/cclm.2011.011.
    1. Kuwahara E., Murakami Y., Okamura T., et al. Increased childhood BMI is associated with young adult serum uric acid levels: a linkage study from Japan. Pediatric Research. 2017;81(2):293–298. doi: 10.1038/pr.2016.213.
    1. Choi H. K., Ford E. S. Prevalence of the metabolic syndrome in individuals with hyperuricemia. American Journal of Medicine. 2007;120(5):442–447. doi: 10.1016/j.amjmed.2006.06.040.
    1. Bussler S., Penke M., Flemming G., et al. Novel insights in the metabolic syndrome in childhood and adolescence. Hormone Research in Paediatrics. 2017;88(3-4):181–193. doi: 10.1159/000479510.
    1. DeBoer M. D., Dong L., Gurka M. J. Racial/ethnic and sex differences in the relationship between uric acid and metabolic syndrome in adolescents: an analysis of national health and nutrition survey 1999–2006. Metabolism. 2012;61(4):554–561. doi: 10.1016/j.metabol.2011.09.003.
    1. Sun H. L., Pei D., Lue K. H., Chen Y. L. Uric acid levels can predict metabolic syndrome and hypertension in adolescents: a 10-year longitudinal study. PLoS One. 2015;10(11) doi: 10.1371/journal.pone.0143786.e0143786
    1. Feig D. I., Johnson R. J. Hyperuricemia in childhood primary hypertension. Hypertension. 2003;42(3):247–252. doi: 10.1161/01.hyp.0000085858.66548.59.
    1. Jones D. P., Richey P. A., Alpert B. S., Li R. Serum uric acid and ambulatory blood pressure in children with primary hypertension. Pediatric Research. 2008;64(5):556–561. doi: 10.1203/pdr.0b013e318183fd7c.
    1. Viazzi F., Antolini L., Giussani M., et al. Serum uric acid and blood pressure in children at cardiovascular risk. Pediatrics. 2013;132(1):e93–e99. doi: 10.1542/peds.2013-0047.
    1. Park B., Lee H. A., Lee S. H., et al. Association between serum levels of uric acid and blood pressure tracking in childhood. American Journal of Hypertension. 2017;30(7):713–718. doi: 10.1093/ajh/hpx037.
    1. Alper A. B., Jr., Chen W., Yau L., Srinivasan S. R., Berenson G. S., Hamm L. L. Childhood uric acid predicts adult blood pressure. Hypertension. 2005;45(1):34–38. doi: 10.1161/.
    1. Yanik M., Feig D. I. Serum urate: a biomarker or treatment target in pediatric hypertension? Current Opinion in Cardiology. 2013;28(4):433–438. doi: 10.1097/HCO.0b013e32836205ff.
    1. Islam A. H. M. W., Yamashita S., Kotani K., et al. Fasting plasma insulin level is an important risk factor for the development of complications in Japanese obese children-results from a cross-sectional and a longitudinal study. Metabolism. 1995;44(4):478–485. doi: 10.1016/0026-0495(95)90055-1.
    1. Sakou I. I., Psaltopoulou T., Sergentanis T. N., et al. Insulin resistance and cardiometabolic risk factors in obese children and adolescents: a hierarchical approach. Journal of Pediatric Endocrinology and Metabolism. 2015;28(5-6):589–596. doi: 10.1515/jpem-2014-0431.
    1. Denzer C., Muche R., Mayer H., Heinze E., Debatin K. M., Wabitsch M. Serum uric acid levels in obese children and adolescents: linkage to testosterone levels and pre-metabolic syndrome. Journal of Pediatric Endocrinology and Metabolism. 2003;16(9):1225–1232. doi: 10.1515/jpem.2003.16.9.1225.
    1. Ko Y. C., Huang M. C., Wang T. N., Chang S. J., Tsai L. Y., Tu H. P. Prevalence and risk factors associated with dyslipidaemia in children and adolescents among ethnic groups in Taiwan. Public Health. 2005;119(6):489–497. doi: 10.1016/j.puhe.2004.08.013.
    1. Narverud I., Retterstøl K., Iversen P. O., et al. Markers of atherosclerotic development in children with familial hypercholesterolemia: a literature review. Atherosclerosis. 2014;235(2):299–309. doi: 10.1016/j.atherosclerosis.2014.05.917.
    1. Pacifico L., Cantisani V., Anania C., et al. Serum uric acid and its association with metabolic syndrome and carotid atherosclerosis in obese children. European Journal of Endocrinology. 2009;160(1):45–52. doi: 10.1530/eje-08-0618.
    1. Ishiro M., Takaya R., Mori Y., et al. Association of uric acid with obesity and endothelial dysfunction in children and early adolescents. Annals of Nutrition and Metabolism. 2012;62(2):169–176. doi: 10.1159/000346227.
    1. Fathallah-Shaykh S. A., Cramer M. T. Uric acid and the kidney. Pediatric Nephrology. 2014;29(6):999–1008. doi: 10.1007/s00467-013-2549-x.
    1. Rodenbach K. E., Schneider M. F., Furth S. L., et al. Hyperuricemia and progression of CKD in children and adolescents: the chronic kidney disease in children (CKiD) cohort study. American Journal of Kidney Diseases. 2015;66(6):984–992. doi: 10.1053/j.ajkd.2015.06.015.
    1. Sharbaf F. G., Assadi F. Effect of allopurinol on the glomerular filtration rate of children with chronic kidney disease. Pediatric Nephrology. 2018;33(8):1405–1409. doi: 10.1007/s00467-018-3943-1.
    1. Hsia S.-H., Chou I.-J., Kuo C.-F., et al. Survival impact of serum uric acid levels in children and adolescents. Rheumatology International. 2013;33(11):2797–2802. doi: 10.1007/s00296-013-2808-y.
    1. August G. P., Caprio S., Fennoy I., et al. Prevention and treatment of pediatric obesity: an endocrine society clinical practice guideline based on expert opinion. Journal of Clinical Endocrinology & Metabolism. 2008;93(12):4576–4599. doi: 10.1210/jc.2007-2458.
    1. Togashi K., Masuda H., Iguchi K. Effect of diet and exercise treatment for obese Japanese children on abdominal fat distribution. Research in Sports Medicine. 2010;18(1):62–70. doi: 10.1080/15438620903423924.
    1. Krzystek-Korpacka M., Patryn E., Kustrzeba-Wojcicka I., Chrzanowska J., Gamian A., Noczynska A. The effect of a one-year weight reduction program on serum uric acid in overweight/obese children and adolescents. Clinical Chemistry and Laboratory Medicine. 2011;49(5):915–921. doi: 10.1515/cclm.2011.130.
    1. Torres R. J., Prior C., Puig J. G. Efficacy and safety of allopurinol in patients with hypoxanthine-guanine phosphoribosyltransferase deficiency. Metabolism. 2007;56(9):1179–1186. doi: 10.1016/j.metabol.2007.04.013.
    1. Harambat J., Bollée G., Daudon M., Ceballos-Picot I., Bensman A., APRT Study Group Adenine phosphoribosyltransferase deficiency in children. Pediatric Nephrology. 2012;27(4):571–579. doi: 10.1007/s00467-011-2037-0.
    1. Smit G. P. The long-term outcome of patients with glycogen storage disease type Ia. European Journal of Pediatrics. 1993;152(1):S52–S55. doi: 10.1007/bf02072089.
    1. Fairbanks L. D., Cameron J. S., Venkat-Raman G., et al. Early treatment with allopurinol in familial juvenile hyerpuricaemic nephropathy (FJHN) ameliorates the long-term progression of renal disease. QJM: An International Journal of Medicine. 2002;95(9):597–607. doi: 10.1093/qjmed/95.9.597.
    1. Soletsky B., Feig D. I. Uric acid reduction rectifies prehypertension in obese adolescents. Hypertension. 2012;60(5):1148–1156. doi: 10.1161/hypertensionaha.112.196980.
    1. Assadi F. Allopurinol enhances the blood pressure lowering effect of enalapril in children with hyperuricemic essential hypertension. Journal of Nephrology. 2014;27(1):51–56. doi: 10.1007/s40620-013-0009-0.
    1. Somkrua R., Eickman E. E., Saokaew S., Lohitnavy M., Chaiyakunapruk N. Association of HLA-B ∗ 5801 allele and allopurinol-induced stevens johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. BMC Medical Genetics. 2011;12(1):p. 118. doi: 10.1186/1471-2350-12-118.
    1. Becker M. A., Kisicki J., Khosravan R., et al. Febuxostat (TMX-67), a novel, non-purine, selective inhibitor of xanthine oxidase, is safe and decreases serum urate in healthy volunteers. Nucleosides, Nucleotides and Nucleic Acids. 2004;23(8-9):1111–1116. doi: 10.1081/ncn-200027372.
    1. Kaku Y., Nishimura M. Febuxostat for hyperuricemia of CKD children. Pediatric Nephrology. 2016;31:p. 1907.
    1. Kishimoto K., Kobayashi R., Hori D., Sano H., Suzuki D., Kobayashi K. Febuxostat as a prophylaxis for tumor lysis syndrome in children with hematological malignancies. Anticancer Research. 2017;37(10):5845–5849. doi: 10.21873/anticanres.12028.
    1. Pui C.-H., Jeha S., Irwin D., Camitta B. Recombinant urate oxidase (rasburicase) in the prevention and treatment of malignancy-associated hyperuricemia in pediatric and adult patients: results of a compassionate-use trial. Leukemia. 2001;15(10):1505–1509. doi: 10.1038/sj.leu.2402235.
    1. Coiffier B., Altman A., Pui C.-H., Younes A., Cairo M. S. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. Journal of Clinical Oncology. 2008;26(16):2767–2778. doi: 10.1200/jco.2007.15.0177.
    1. Cheuk D. K., Chiang A. K., Chan G. C., Ha S. Y. Urate oxidase for the prevention and treatment of tumor lysis syndrome in children with cancer. Cochrane Database of Systematic Reviews. 2017;16(6) doi: 10.1002/14651858.cd006945.CD006945

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit