Skip to main content

Advertisement

SpringerLink
Log in

Uric acid could be a marker of cardiometabolic risk and disease severity in children with juvenile idiopathic arthritis

  • Research
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

In addition to disease-specific complications, juvenile idiopathic arthritis (JIA) has been linked to metabolic impairments in adults. Recent data supported the usefulness of uric acid (UA) as risk factor for cardiometabolic derangements. Given the lack of pediatric evidence in this field, we aimed to explore this association in a cohort of children diagnosed with JIA. We retrospectively evaluated 113 children diagnosed with JIA classified according to the International League of Association for Rheumatology (ILAR) criteria attending our Rheumatology Clinic. Both clinical and biochemical assessments were performed. Participants were stratified in four groups according to quartiles of serum UA. Disease activity was calculated by the Juvenile Arthritis Disease Activity Score 10 (JADAS-10) joint reduced count, and cut-offs for disease states were applied. Patients belonging to the highest UA quartile showed higher serum triglycerides, total cholesterol, creatinine, and glucose levels (p = 0.01, p = 0.025, p = 0.04, and p = 0.005, respectively) and lower HDL cholesterol values (p < 0.0001) than subjects belonging to the lowest quartiles. Ferritin, erythrocyte sedimentation rate levels, and age at disease onset did not significantly differ across UA quartiles (all p > 0.05). As activity disease index, JADAS-10 score significantly increased across UA quartiles (p = 0.009).

Conclusion: Children with JIA presented with a worse cardiometabolic profile and a greater disease severity across UA quartiles. Our findings suggest that in clinical practice, UA might represent a useful marker of cardiometabolic risk and disease severity in children with JIA.

What is Known:

• JIA has been linked to metabolic derangements in adulthood.

• UA has been recognized as a marker of cardiometabolic risk both in adults and children.

What is New:

• Children with JIA belonging to the highest UA quartile showed a worse cardiometabolic profile and a greater disease severity.

• UA might represent a helpful marker not only of cardiometabolic risk but also of disease severity in children with JIA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

BMI:

Body mass index

CVD:

Cardiovascular disease

DMARDs:

Disease-modifying anti-rheumatic drugs

ILAR:

International League of Association for Rheumatology

IR:

Insulin resistance

JIA:

Juvenile idiopathic arthritis

JADAS-10:

Juvenile Arthritis Disease Activity Score 10

MetS:

Metabolic syndrome

NSAIDs:

Non-steroidal anti-inflammatory drugs

T2D:

Type 2 diabetes

UA:

Uric acid

References

  1. Ravelli A, Martini A (2007) Juvenile idiopathic arthritis. Lancet 369(9563):767–778

    CAS  Google Scholar 

  2. Petty RE, Southwood TR, Manners P et al (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 31(2):390–392

    Google Scholar 

  3. Ringold S, Weiss PF, Beukelman T et al (2013) 2013 update of the 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: recommendations for the medical therapy of children with systemic juvenile idiopathic arthritis and tuberculosis screening among children receiving biologic medications. Arthritis Rheum 65(10):2499–2512

    Google Scholar 

  4. Beukelman T, Patkar NM, Saag KG et al (2011) 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res (Hoboken) 63(4):465–482

    Google Scholar 

  5. Espinosa M, Gottlieb BS (2012) Juvenile idiopathic arthritis. Pediatr Rev 33(7):303–313

    Google Scholar 

  6. Sule S, Fontaine K (2018) Metabolic syndrome in adults with a history of juvenile arthritis. Open Access Rheumatol 10:67–72

    Google Scholar 

  7. Zanette Cde A, Machado SH, Brenol JC, Xavier RM (2010) Metabolic syndrome and juvenile idiopathic arthritis. Rev Bras Reumatol 50(2):190–204

    Google Scholar 

  8. Lv Q, Meng XF, He FF et al (2013) High serum uric acid and increased risk of type 2 diabetes: a systemic review and meta-analysis of prospective cohort studies. PLoS ONE 8(2):e56864

    CAS  Google Scholar 

  9. Yuan H, Yu C, Li X et al (2015) Serum uric acid levels and risk of metabolic syndrome: a dose-response meta-analysis of prospective studies. J Clin Endocrinol Metab 100(11):4198–4207

    CAS  Google Scholar 

  10. Richette P, Perez-Ruiz F (2013) Serum uric acid and metabolic risk. Curr Med Res Opin 29(Suppl 3):9–15

    CAS  Google Scholar 

  11. Russo E, Leoncini G, Esposito P, Garibotto G, Pontremoli R, Viazzi F (2020) Fructose and uric acid: major mediators of cardiovascular disease risk starting at pediatric age. Int J Mol Sci 21(12)

  12. Shi Q, Wang R, Zhang H, Shan Y, Ye M, Jia B (2021) Association between serum uric acid and cardiovascular disease risk factors in adolescents in America: 2001–2018. PLoS ONE 16(8):e0254590

    CAS  Google Scholar 

  13. Di Bonito P, Valerio G, Licenziati MR et al (2021) Uric acid, impaired fasting glucose and impaired glucose tolerance in youth with overweight and obesity. Nutr Metab Cardiovasc Dis 31(2):675–680

    Google Scholar 

  14. Goli P, Riahi R, Daniali SS, Pourmirzaei M, Kelishadi R (2020) Association of serum uric acid concentration with components of pediatric metabolic syndrome: a systematic review and meta-analysis. J Res Med Sci 25:43

    CAS  Google Scholar 

  15. Ford ES, Li C, Cook S, Choi HK (2007) Serum concentrations of uric acid and the metabolic syndrome among US children and adolescents. Circulation 115(19):2526–2532

    CAS  Google Scholar 

  16. Di Bonito P, Valerio G, Licenziati MR et al (2022) Uric acid versus metabolic syndrome as markers of fatty liver disease in young people with overweight/obesity. Diabetes Metab Res Rev e3559

  17. Giani T, De Masi S, Maccora I et al (2019) The influence of overweight and obesity on treatment response in juvenile idiopathic arthritis. Front Pharmacol 10:637

    CAS  Google Scholar 

  18. Diaz-Cordoves Rego G, Nunez-Cuadros E, Mena-Vazquez N et al (2021) Adiposity is related to inflammatory disease activity in juvenile idiopathic arthritis. J Clin Med 10(17)

  19. Di Bonito P, Pacifico L, Licenziati MR et al (2020) Elevated blood pressure, cardiometabolic risk and target organ damage in youth with overweight and obesity. Nutr Metab Cardiovasc Dis 30(10):1840–1847

    Google Scholar 

  20. Di Sessa A, Umano GR, Cirillo G et al (2020) The rs72613567: TA variant in the hydroxysteroid 17-beta dehydrogenase 13 gene reduces liver damage in obese children. J Pediatr Gastroenterol Nutr 70(3):371–374

    Google Scholar 

  21. Ravelli A, Consolaro A, Horneff G et al (2018) Treating juvenile idiopathic arthritis to target: recommendations of an international task force. Ann Rheum Dis 77(6):819–828

    Google Scholar 

  22. Consolaro A, Ruperto N, Bazso A et al (2009) Development and validation of a composite disease activity score for juvenile idiopathic arthritis. Arthritis Rheum 61(5):658–666

    Google Scholar 

  23. Consolaro A, Bracciolini G, Ruperto N et al (2012) Remission, minimal disease activity, and acceptable symptom state in juvenile idiopathic arthritis: defining criteria based on the juvenile arthritis disease activity score. Arthritis Rheum 64(7):2366–2374

    Google Scholar 

  24. Dessein PH, Tobias M, Veller MG (2006) Metabolic syndrome and subclinical atherosclerosis in rheumatoid arthritis. J Rheumatol 33(12):2425–2432

    Google Scholar 

  25. Chung CP, Oeser A, Solus JF et al (2008) Prevalence of the metabolic syndrome is increased in rheumatoid arthritis and is associated with coronary atherosclerosis. Atherosclerosis 196(2):756–763

    CAS  Google Scholar 

  26. Tagi VM, Samvelyan S, Chiarelli F (2020) Treatment of metabolic syndrome in children. Horm Res Paediatr 93(4):215–225

    CAS  Google Scholar 

  27. Gesteiro E, Megia A, Guadalupe-Grau A, Fernandez-Veledo S, Vendrell J, Gonzalez-Gross M (2021) Early identification of metabolic syndrome risk: a review of reviews and proposal for defining pre-metabolic syndrome status. Nutr Metab Cardiovasc Dis 31(9):2557–2574

    CAS  Google Scholar 

  28. Borghi C, Agabiti-Rosei E, Johnson RJ et al (2020) Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease. Eur J Intern Med 80:1–11

    CAS  Google Scholar 

  29. Feig DI (2009) Uric acid: a novel mediator and marker of risk in chronic kidney disease? Curr Opin Nephrol Hypertens 18(6):526–530

    CAS  Google Scholar 

  30. Luciano R, Shashaj B, Spreghini M et al (2017) Percentiles of serum uric acid and cardiometabolic abnormalities in obese Italian children and adolescents. Ital J Pediatr 43(1):3

    Google Scholar 

  31. Guzman J, Kerr T, Ward LM et al (2017) Growth and weight gain in children with juvenile idiopathic arthritis: results from the ReACCh-Out cohort. Pediatr Rheumatol Online J 15(1):68

    Google Scholar 

  32. Merwin S, Mackey E, Sule S (2021) US NHANES Data 2013–2016: increased risk of severe obesity in individuals with history of juvenile idiopathic arthritis. Pediatr Rheumatol Online J 19(1):119

    Google Scholar 

  33. Schenck S, Niewerth M, Sengler C et al (2015) Prevalence of overweight in children and adolescents with juvenile idiopathic arthritis. Scand J Rheumatol 44(4):288–295

    CAS  Google Scholar 

  34. Dixon JB (2010) The effect of obesity on health outcomes. Mol Cell Endocrinol 316(2):104–108

    CAS  Google Scholar 

  35. Gicchino MF, Di Sessa A, Guarino S, Miraglia Del Giudice E, Olivieri AN, Marzuillo P (2021) Prevalence of and factors associated to chronic kidney disease and hypertension in a cohort of children with juvenile idiopathic arthritis. Eur J Pediatr 180(2):655–661

    CAS  Google Scholar 

  36. Al-Daghri NM, Al-Attas OS, Wani K, Sabico S, Alokail MS (2017) Serum uric acid to creatinine ratio and risk of metabolic syndrome in Saudi type 2 diabetic patients. Sci Rep 7(1):12104

    Google Scholar 

  37. Silva NR, Goncalves CET, Goncalves DLN, Cotta RMM, da Silva LS (2021) Association of uric acid and uric acid to creatinine ratio with chronic kidney disease in hypertensive patients. BMC Nephrol 22(1):311

    CAS  Google Scholar 

  38. Harlan WR, Cornoni-Huntley J, Leaverton PE (1979) Physiologic determinants of serum urate levels in adolescence. Pediatrics 63(4):569–575

    CAS  Google Scholar 

  39. Dai C, Wang C, Xia F et al (2021) Age and gender-specific reference intervals for uric acid level in children aged 5–14 years in Southeast Zhejiang Province of China: hyperuricemia in children may need redefinition. Front Pediatr 9:560720

    Google Scholar 

  40. Copur S, Demiray A, Kanbay M (2022) Uric acid in metabolic syndrome: does uric acid have a definitive role? Eur J Intern Med

  41. Kushiyama A, Nakatsu Y, Matsunaga Y et al (2016) Role of uric acid metabolism-related inflammation in the pathogenesis of metabolic syndrome components such as atherosclerosis and nonalcoholic steatohepatitis. Mediators Inflamm 2016:8603164

    Google Scholar 

  42. Spiga R, Marini MA, Mancuso E et al (2017) Uric acid is associated with inflammatory biomarkers and induces inflammation via activating the NF-kappaB signaling pathway in HepG2 Cells. Arterioscler Thromb Vasc Biol 37(6):1241–1249

    CAS  Google Scholar 

  43. Ghaemi-Oskouie F, Shi Y (2011) The role of uric acid as an endogenous danger signal in immunity and inflammation. Curr Rheumatol Rep 13(2):160–166

    CAS  Google Scholar 

  44. Sarkar S, Alam MM, Das G, Datta S (2017) Inflammatory markers and disease activity in juvenile idiopathic arthritis. Indian J Pediatr 84(5):349–356

    Google Scholar 

  45. Swart JF, de Roock S, Prakken BJ (2016) Understanding inflammation in juvenile idiopathic arthritis: how immune biomarkers guide clinical strategies in the systemic onset subtype. Eur J Immunol 46(9):2068–2077

    CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to all patients and their families.

Author information

Authors and Affiliations

  1. Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Via L. De Crecchio n° 2, 80138, Naples, Italy

    Maria Francesca Gicchino, Pierluigi Marzuillo, Sarah Zarrilli, Rosa Melone, Stefano Guarino, Emanuele Miraglia del Giudice, Alma Nunzia Olivieri & Anna Di Sessa

Authors
  1. Maria Francesca Gicchino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pierluigi Marzuillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sarah Zarrilli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rosa Melone
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stefano Guarino
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Emanuele Miraglia del Giudice
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alma Nunzia Olivieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anna Di Sessa
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MFG and ADS drafted the paper. EMDG, ANO, and ADS participated in the conception and the design of the study. SZ, RM, and SG examined the patients and collected anthropometric and biochemical data. ADS and PM performed the data analysis. ADS, EMDG, ANO, and PM supervised the design and execution of the study. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Anna Di Sessa.

Ethics declarations

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Research Ethical Committee of the University of Campania “Luigi Vanvitelli” (protocol code 834/2016).

Consent to participate

Informed consent was obtained from all individual participants included in the study. Patients’ data were treated to guarantee confidentiality.

Consent for publication

Not applicable.

Conflict of interest

The authors declare no competing interests.

Additional information

Communicated by Peter de Winter

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gicchino, M.F., Marzuillo, P., Zarrilli, S. et al. Uric acid could be a marker of cardiometabolic risk and disease severity in children with juvenile idiopathic arthritis. Eur J Pediatr 182, 149–154 (2023). https://doi.org/10.1007/s00431-022-04657-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-022-04657-8

Keywords

Search

Navigation