Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Clinical Research Article
  • Published:

Development of a prediction model for progression of coronary artery lesions in Kawasaki disease

Pediatric Research volume 95, pages 1041–1050 (2024)Cite this article

Abstract

Backgrounds

This study aimed to identify risk factors for the progression of coronary artery lesions (CALs) in children with Kawasaki disease (KD) and to develop a nomogram prediction model.

Methods

This is a retrospective case-control study in which the participants were categorized into three groups based on the changes of the maximum Z score (Zmax) of coronary arteries at the 1-month follow-up compared with the baseline Zmax: CALs-progressed, CALs-improved, and CALs-unchanged.

Results

Of total 387 patients, 65 (27%), 319 (73%), and 3 (0.7%) patients were categorized into CALs-progressed group, CALs-improved group, and CALs-unchanged group, respectively. Six independent factors associated with CALs progression were identified, including initial IVIG resistance, baseline Zmax, the number of coronary arteries involved, C-reactive protein, albumin, and soluble interleukin-2 receptor (odds ratio: 7.19, 1.51, 2.32, 1.52, 0.86, and 1.46, respectively; all P-values < 0.01). The nomogram prediction model including these six independent risk factors yielded an area under the curve (AUC) of 0.80 (95% confidence interval, 0.74 to 0.86). The accuracy of this model reached 81.7% after the Monte-Carlo Bootstrapping 1000 repetitions.

Conclusions

The nomogram prediction model can identify children at high risk for the progression of CALs at early stages.

Impact

  • Six independent factors associated with CALs progression were identified, including initial IVIG resistance, baseline Zmax, the number of coronary arteries involved, CRP, ALB, and sIL-2R.

  • The prediction model we constructed can identify children at high risk for the progression of CALs at early stages and help clinicians make individualized treatment plans.

  • Prospective, multi-centered studies with larger sample sizes are warranted to validate the power of this prediction model in children with KD.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The flowchart of the study.
Fig. 2: The interaction effects of four significant factors.
Fig. 3: ROC curves for 3 models.
Fig. 4: Prediction nomogram model of CALs progression and related calibration curve.
Fig. 5: Decision curves analysis for the prediction nomogram model.

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. McCrindle, B. W. et al. Diagnosis, treatment, and long-term management of kawasaki disease: a scientific statement for health professionals from the american heart association. Circulation 135, e927–e999 (2017).

    PubMed  Google Scholar 

  2. Xie, L. P. et al. Epidemiologic features of kawasaki disease in shanghai from 2013 through 2017. J. Epidemiol. 30, 429–435 (2020).

    PubMed  PubMed Central  Google Scholar 

  3. Ae, R. et al. Epidemiology, treatments, and cardiac complications in patients with kawasaki disease: the nationwide survey in Japan, 2017-2018. J. Pediatr.-Us 225, 23–29 (2020).

    Google Scholar 

  4. Chen, J. J. et al. Epidemiologic features of kawasaki disease in Shanghai from 2008 through 2012. Pediatr. Infect. Dis. J. 35, 7–12 (2016).

    CAS  PubMed  Google Scholar 

  5. Baer, A. Z. et al. Prevalence of coronary artery lesions on the initial echocardiogram in Kawasaki syndrome. Arch. Pediatr. Adolesc. Med. 160, 686–690 (2006).

    PubMed  Google Scholar 

  6. Dominguez, S. R., Anderson, M. S., El-Adawy, M. & Glodé, M. P. Preventing coronary artery abnormalities: a need for earlier diagnosis and treatment of Kawasaki disease. Pediatr. Infect. Dis. J. 31, 1217–1220 (2012).

    PubMed  Google Scholar 

  7. Fuse, S., Mori, T., Kuroiwa, Y. & Hirakawa, S. On what day of illness does the dilatation of coronary arteries in patients with Kawasaki disease begin? Circ. J. 82, 247–250 (2017).

    PubMed  Google Scholar 

  8. McCrindle, B. W. et al. Coronary artery involvement in children with Kawasaki disease: risk factors from analysis of serial normalized measurements. Circulation 116, 174–179 (2007).

    PubMed  Google Scholar 

  9. Ae, R. et al. Outcomes in Kawasaki disease patients with coronary artery abnormalities at admission. Am. Heart J. 225, 120–128 (2020).

    PubMed  Google Scholar 

  10. Fukazawa, R. et al. JCS/JSCS 2020 guideline on diagnosis and management of cardiovascular sequelae in Kawasaki disease. Circ. J. 84, 1348–1407 (2020).

    CAS  PubMed  Google Scholar 

  11. Liu, L. et al. Risk factors associated with progression and persistence of small- and medium-sized coronary artery aneurysms in Kawasaki disease: a prospective cohort study. Eur. J. Pediatr. 179, 891–900 (2020).

    CAS  PubMed  Google Scholar 

  12. Miyata, K. et al. Infliximab for intensification of primary therapy for patients with Kawasaki disease and coronary artery aneurysms at diagnosis. Arch. Dis. Child 108, 833–838 (2023).

    PubMed  Google Scholar 

  13. Dionne A. et al. Treatment Intensification in Patients With Kawasaki Disease and Coronary Aneurysm at Diagnosis. Pediatrics 143, (2019).

  14. Lin, M. T. et al. Acute and late coronary outcomes in 1073 patients with Kawasaki disease with and without intravenous γ-immunoglobulin therapy. Arch. Dis. Child 100, 542–547 (2015).

    ADS  PubMed  Google Scholar 

  15. Suzuki, T. et al. Z-score is a possible predictor of the risk of coronary artery lesion development in patients with Kawasaki disease in Japan. Eur. J. Pediatr. 180, 2797–2805 (2021).

    PubMed  Google Scholar 

  16. Iio, K. et al. Risk Factors of Coronary Artery Aneurysms in Kawasaki Disease with a Low Risk of Intravenous Immunoglobulin Resistance: An Analysis of Post RAISE. J. Pediatr.-Us 240, 158–163 (2022).

    CAS  Google Scholar 

  17. Miyata, K. et al. Risk factors of coronary artery abnormalities and resistance to intravenous immunoglobulin plus corticosteroid therapy in severe kawasaki disease: an analysis of post RAISE. Circ. Cardiovasc Qual. Outcomes 14, e7191 (2021).

    Google Scholar 

  18. Xia, Y. et al. Albumin level and progression of coronary artery lesions in Kawasaki disease: A retrospective cohort study. Front Pediatr. 10, 947059 (2022).

    PubMed  PubMed Central  Google Scholar 

  19. Kobayashi, T. et al. A New Z score curve of the coronary arterial internal diameter using the Lambda-Mu-Sigma Method in a Pediatric Population. J. Am. Soc. Echocardiog 29, 794–801 (2016).

    Google Scholar 

  20. Kato, T. et al. Analysis of Coronary Arterial Aneurysm Regression in Patients With Kawasaki Disease by Aneurysm Severity: Factors Associated With Regression. J. Am. Heart Assoc. 12, e22417 (2023).

    Google Scholar 

  21. Friedman K. G. et al. Coronary Artery Aneurysms in Kawasaki Disease: Risk Factors for Progressive Disease and Adverse Cardiac Events in the US Population. J Am Heart Assoc 5, (2016).

  22. Narayan H. K. et al. Clinical Presentation and Outcomes of Kawasaki Disease in Children From Latin America: A Multicenter Observational Study from the REKAMLATINA Network. J Pediatr-Us (2023).

  23. Hu, J. & Ren, W. Analysis of the Risk Factors in Prognosis of Kawasaki Disease With Coronary Artery Lesions. Front Pediatr. 9, 798148 (2021).

    PubMed  PubMed Central  Google Scholar 

  24. Lega, J. C. et al. Extracoronary echocardiographic findings as predictors of coronary artery lesions in the initial phase of Kawasaki disease. Arch. Dis. Child 98, 97–102 (2013).

    PubMed  Google Scholar 

  25. Tang, Y. et al. Coronary artery aneurysm regression after Kawasaki disease and associated risk factors: a 3-year follow-up study in East China. Clin. Rheumatol. 37, 1945–1951 (2018).

    PubMed  Google Scholar 

  26. Miura, M. et al. Association of severity of coronary artery aneurysms in patients with kawasaki disease and risk of later coronary events. JAMA PEDIATR 172, e180030 (2018).

    PubMed  PubMed Central  Google Scholar 

  27. Xie, T. et al. Predictors for intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease. Pediatr. Rheumatol. 15, 17 (2017).

    Google Scholar 

  28. Nandi, A., Pal, P. & Basu, S. A comparison of serum IL6 and CRP levels with respect to coronary changes and treatment response in Kawasaki disease patients: a prospective study. Rheumatol. Int. 39, 1797–1801 (2019).

    CAS  PubMed  Google Scholar 

  29. Noval, R. M. & Arditi, M. Kawasaki disease: pathophysiology and insights from mouse models. Nat. Rev. Rheumatol. 16, 391–405 (2020).

    Google Scholar 

  30. Brown, T. J. et al. CD8 T lymphocytes and macrophages infiltrate coronary artery aneurysms in acute Kawasaki disease. J. Infect. Dis. 184, 940–943 (2001).

    CAS  PubMed  Google Scholar 

  31. Takahashi, K., Oharaseki, T. & Yokouchi, Y. Histopathological aspects of cardiovascular lesions in Kawasaki disease. Int J. Rheum. Dis. 21, 31–35 (2018).

    CAS  PubMed  Google Scholar 

  32. Damoiseaux, J. The IL-2 - IL-2 receptor pathway in health and disease: The role of the soluble IL-2 receptor. Clin. Immunol. 218, 108515 (2020).

    CAS  PubMed  Google Scholar 

  33. Zhang, C. et al. Predictive Role of IL-2R and IL-10 in the Anti-inflammatory Response and Antiplatelet Therapy of Kawasaki Disease: A Retrospective Study. Mediat Inflamm. 2022, 4917550 (2022).

    Google Scholar 

  34. Barron, K. S. et al. Soluble interleukin-2 receptors in children with Kawasaki syndrome. Arthritis Rheum. 33, 1371–1377 (1990).

    CAS  PubMed  Google Scholar 

  35. Lin, C. Y., Lin, C. C., Hwang, B. & Chiang, B. N. Cytokines predict coronary aneurysm formation in Kawasaki disease patients. Eur. J. Pediatr. 152, 309–312 (1993).

    CAS  PubMed  Google Scholar 

  36. Hamada, H. et al. Efficacy of primary treatment with immunoglobulin plus ciclosporin for prevention of coronary artery abnormalities in patients with Kawasaki disease predicted to be at increased risk of non-response to intravenous immunoglobulin (KAICA): a randomised controlled, open-label, blinded-endpoints, phase 3 trial. Lancet 393, 1128–1137 (2019).

    CAS  PubMed  Google Scholar 

  37. Liddicoat, A. M. & Lavelle, E. C. Modulation of innate immunity by cyclosporine A. Biochem Pharm. 163, 472–480 (2019).

    CAS  PubMed  Google Scholar 

  38. Fric, J. et al. NFAT control of innate immunity. Blood 120, 1380–1389 (2012).

    CAS  PubMed  Google Scholar 

  39. El, C. H. & Hassoun, P. M. Immune and inflammatory mechanisms in pulmonary arterial hypertension. Prog. Cardiovasc Dis. 55, 218–228 (2012).

    Google Scholar 

  40. Hamada, H. et al. Inflammatory cytokine profiles during Cyclosporin treatment for immunoglobulin-resistant Kawasaki disease. Cytokine 60, 681–685 (2012).

    CAS  PubMed  Google Scholar 

  41. Wang, Y. et al. The role of Ca(2+)/NFAT in Dysfunction and Inflammation of Human Coronary Endothelial Cells induced by Sera from patients with Kawasaki disease. Sci. Rep.-Uk 10, 4706 (2020).

    ADS  CAS  Google Scholar 

  42. Sun, Y. et al. The activation of CaN/NFAT signaling pathway in macrophages aggravated Lactobacillus casei cell wall extract-induced Kawasaki disease vasculitis. Cytokine 169, 156304 (2023).

    CAS  PubMed  Google Scholar 

  43. Terai, M. et al. Prognostic impact of vascular leakage in acute Kawasaki disease. Circulation 108, 325–330 (2003).

    PubMed  Google Scholar 

  44. Son M. et al. Predicting Coronary Artery Aneurysms in Kawasaki Disease at a North American Center: An Assessment of Baseline z Scores. J Am Heart Assoc 6 (2017).

  45. Tse, S. M., Silverman, E. D., McCrindle, B. W. & Yeung, R. S. Early treatment with intravenous immunoglobulin in patients with Kawasaki disease. J. Pediatr.-Us 140, 450–455 (2002).

    CAS  Google Scholar 

  46. Burns, J. C., Hoshino, S. & Kobayashi, T. Kawasaki disease: an essential comparison of coronary artery aneurysm criteria. Lancet Child Adolesc. 2, 840–841 (2018).

    Google Scholar 

  47. de Zorzi, A. et al. Coronary artery dimensions may be misclassified as normal in Kawasaki disease. J. Pediatr.-Us 133, 254–258 (1998).

    Google Scholar 

  48. Ae, R. et al. Differences in sensitivity between the japanese and z score criteria for detecting coronary artery abnormalities resulting from kawasaki disease. Pediatr. Cardiol. 44, 153–160 (2023).

    PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Dr. Rui Sun for her assistance in data analysis.

Funding

This study was supported by the Clinical and Basic Integration Project of Capital Institute of Pediatrics (Grant No. JHYJ-2023-01)

Author information

Authors and Affiliations

  1. Department of Cardiology, Children’s Hospital Capital Institute of Pediatrics, Beijing, China

    Dan Xu, Ye-Shi Chen, Chen-Hui Feng, Ai-Mei Cao & Xiao-Hui Li

  2. Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China

    Dan Xu & Xiao-Hui Li

  3. Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China

    Ye-Shi Chen, Chen-Hui Feng & Xiao-Hui Li

Authors
  1. Dan Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ye-Shi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chen-Hui Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ai-Mei Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiao-Hui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization/design: D.X., X.-H.L. Funding acquisition: X.-H.L. Methodology: D.X., X.-H.L. Data curation: D.X., C.-H.F. Investigation: D.X., C.-H.F., A.-M.C. Formal analysis: D.X. Supervision/oversight: A.-M.C. Resources: X.-H.L. Writing-Original Draft: D.X. Writing-Review & Editing: Y.-S.C., X.-H.L. Final approval of manuscript: All authors.

Corresponding author

Correspondence to Xiao-Hui Li.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The study protocol was reviewed and approved by the Institutional Review Board of Capital Institute of Pediatrics (Ref. No. SHERLL2023048).

Informed consent

The requirement to obtain informed written consent was waived owing to the nature of retrospective studies.

Additional information

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 (e.g. a society or other partner) 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

Xu, D., Chen, YS., Feng, CH. et al. Development of a prediction model for progression of coronary artery lesions in Kawasaki disease. Pediatr Res 95, 1041–1050 (2024). https://doi.org/10.1038/s41390-023-02931-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41390-023-02931-5

Search

Advanced search

Quick links