Skip to main content

Advertisement

SpringerLink
Log in

Pro-brain natriuretic peptide (ProBNP) levels in North Indian children with Kawasaki disease

  • Original Article - Biomarkers
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

The diagnosis of Kawasaki disease (KD), a common pediatric vasculitis, is based solely on clinical criteria. There is a need for a robust laboratory marker that can help differentiate KD from other acute, febrile, childhood illnesses and also to predict cardiac involvement. We conducted a cross-sectional study of 25 consecutive patients admitted with diagnosis of KD from January 2013 to April 2014 and compared them with age- and sex-matched febrile controls. We studied the serum pro-brain natriuretic peptide (ProBNP) [ProBNP and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) levels], a marker of myocardial dysfunction, in children with KD in acute and convalescent phases of disease. These levels were also estimated in febrile controls for comparison. The ProBNP (ProBNP and NT-ProBNP) levels were much higher in the acute phase of the KD patients compared to levels in the convalescent phase of KD (p = 0.000014). Similarly, the levels in the acute phase were higher when compared to the age- and sex-matched febrile controls (p = 0.000126). The receiver operating curve (ROC) analysis for the ProBNP levels in the acute phase of KD yielded an area under the curve of 0.954 ± 0.034 (p < 0.000, 95 % CI 0.886–1.0). Based on ROC analysis, a cutoff of 1025 pg/mL for ProBNP levels in the acute phase of KD had 88 % sensitivity and 96 % specificity for the diagnosis of KD. A lower cut-off of 514 pg/mL yielded a 100 % sensitivity and 80 % specificity for the diagnosis of KD. The ProBNP levels were higher in those with coronary artery abnormalities (CAA) compared to those without CAA in both acute (p = 0.013) and convalescent (p = 0.045) phases. ProBNP levels may be used as a surrogate marker for the differentiation of KD from other febrile, infectious illnesses and may also predict the involvement of coronary arteries.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC et al (2004) Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the committee on rheumatic fever, endocarditis and Kawasaki disease, council on cardiovascular disease in the Young, American heart association. Circulation 110(17):2747–2771

    Article  PubMed  Google Scholar 

  2. Son MBF, Newburger JW (2013) Kawasaki disease. Pediatr Rev Am Acad Pediatr 34(4):151–162

    Article  Google Scholar 

  3. Suzuki A, Kamiya T, Kuwahara N, Ono Y, Kohata T, Takahashi O et al (1986) Coronary arterial lesions of Kawasaki disease: cardiac catheterization findings of 1100 cases. Pediatr Cardiol 7(1):3–9

    Article  CAS  PubMed  Google Scholar 

  4. Duarte R, Cisneros S, Fernandez G, Castellon D, Cattani C, Melo CA et al (2010) Kawasaki disease: a review with emphasis on cardiovascular complications. Insights Imaging 1(4):223–231

    Article  PubMed  PubMed Central  Google Scholar 

  5. Cimaz R, Sundel R (2009) Atypical and incomplete Kawasaki disease. Best Pract Res Clin Rheumatol 23(5):689–697

    Article  CAS  PubMed  Google Scholar 

  6. Dahdah N, Siles A, Fournier A, Cousineau J, Delvin E, Saint-Cyr C et al (2009) Natriuretic peptide as an adjunctive diagnostic test in the acute phase of Kawasaki disease. Pediatr Cardiol 30(6):810–817

    Article  PubMed  Google Scholar 

  7. Takahashi M (1989) Myocarditis in Kawasaki syndrome. A minor villain? Circulation 79(6):1398–1400

    Article  CAS  PubMed  Google Scholar 

  8. Tsai S-H, Lin Y-Y, Chu S-J, Hsu C-W, Cheng S-M (2010) Interpretation and use of natriuretic peptides in non-congestive heart failure settings. Yonsei Med J 51(2):151–163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Nir A, Bar-Oz B, Perles Z, Brooks R, Korach A, Rein AJJT (2004) N-terminal pro-B-type natriuretic peptide: reference plasma levels from birth to adolescence. Elevated levels at birth and in infants and children with heart diseases. Acta Paediatr 93(5):603–607

    Article  CAS  PubMed  Google Scholar 

  10. Dallaire F, Dahdah N (2011) New equations and a critical appraisal of coronary artery Z scores in healthy children. J Am Soc Echocardiogr Off Publ Am Soc Echocardiogr 24(1):60–74

    Article  Google Scholar 

  11. Abstracts of the 10th International Kawasaki Disease Symposium (February 7–10, 2012) Kyoto, Japan. Pediatr Int Off J Jpn Pediatr Soc. 54(Suppl 1):38–142

  12. Singh S, Aulakh R, Bhalla AK, Suri D, Manojkumar R, Narula N et al (2011) Is Kawasaki disease incidence rising in Chandigarh, North India? Arch Dis Child 96(2):137–140

    Article  PubMed  Google Scholar 

  13. Singh S, Aulakh R (2010) Kawasaki disease and Henoch Schonlein purpura: changing trends at a tertiary care hospital in north India (1993–2008). Rheumatol Int 30(6):771–774

    Article  PubMed  Google Scholar 

  14. Newburger JW, Takahashi M, Burns JC, Beiser AS, Chung KJ, Duffy CE et al (1986) The treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med 315(6):341–347

    Article  CAS  PubMed  Google Scholar 

  15. Durongpisitkul K, Gururaj VJ, Park JM, Martin CF (1995) The prevention of coronary artery aneurysm in Kawasaki disease: a meta-analysis on the efficacy of aspirin and immunoglobulin treatment. Pediatrics 96(6):1057–1061

    CAS  PubMed  Google Scholar 

  16. De Rosa G, Pardeo M, Rigante D (2007) Current recommendations for the pharmacologic therapy in Kawasaki syndrome and management of its cardiovascular complications. Eur Rev Med Pharmacol Sci 11(5):301–308

    PubMed  Google Scholar 

  17. Rigante D, Valentini P, Rizzo D, Leo A, De Rosa G, Onesimo R et al (2010) Responsiveness to intravenous immunoglobulins and occurrence of coronary artery abnormalities in a single-center cohort of Italian patients with Kawasaki syndrome. Rheumatol Int 30(6):841–846

    Article  CAS  PubMed  Google Scholar 

  18. Burns JC, Newburger JW (2012) Genetics insights into the pathogenesis of Kawasaki disease. Circ Cardiovasc Genet 5(3):277–278

    Article  PubMed  Google Scholar 

  19. Burgner D, Harnden A (2005) Kawasaki disease: what is the epidemiology telling us about the etiology? Int J Infect Dis IJID Off Publ Int Soc Infect Dis 9(4):185–194

    Google Scholar 

  20. Principi N, Rigante D, Esposito S (2013) The role of infection in Kawasaki syndrome. J Infect 67(1):1–10

    Article  PubMed  Google Scholar 

  21. Dahdah N (2010) Not just coronary arteritis, Kawasaki disease is a myocarditis, too. J Am Coll Cardiol 55(14):1507–1508

    Article  PubMed  Google Scholar 

  22. Yutani C, Go S, Kamiya T, Hirose O, Misawa H, Maeda H et al (1981) Cardiac biopsy of Kawasaki disease. Arch Pathol Lab Med 105(9):470–473

    CAS  PubMed  Google Scholar 

  23. Kao CH, Hsieh KS, Chen YC, Wang YL, Wang SJ, Yeh SH (1995) Labeled WBC cardiac imaging and two-dimensional echocardiography to evaluate high-dose gamma globulin treatment in Kawasaki disease. Clin Nucl Med 20(9):813–816

    Article  CAS  PubMed  Google Scholar 

  24. Nir A, Lindinger A, Rauh M, Bar-Oz B, Laer S, Schwachtgen L et al (2009) NT-pro-B-type natriuretic peptide in infants and children: reference values based on combined data from four studies. Pediatr Cardiol 30(1):3–8

    Article  PubMed  Google Scholar 

  25. Kawamura T, Wago M, Kawaguchi H, Tahara M, Yuge M (2000) Plasma brain natriuretic peptide concentrations in patients with Kawasaki disease. Pediatr Int Off J Jpn Pediatr Soc 42(3):241–248

    Article  CAS  Google Scholar 

  26. Kurotobi S, Kawakami N, Shimizu K, Aoki H, Nasuno S, Takahashi K et al (2005) Brain natriuretic peptide as a hormonal marker of ventricular diastolic dysfunction in children with Kawasaki disease. Pediatr Cardiol 26(4):425–430

    Article  CAS  PubMed  Google Scholar 

  27. Kishimoto S, Suda K, Teramachi Y, Nishino H, Kudo Y, Ishii H et al (2011) Increased plasma type B natriuretic peptide in the acute phase of Kawasaki disease. Pediatr Int Off J Jpn Pediatr Soc 53(5):736–741

    Article  CAS  Google Scholar 

  28. Sun Y-P, Wang W-D, Zheng X-C, Wang J-J, Ma S-C, Xu Y-J (2010) Levels of serum brain natriuretic peptide and the correlation to heart function in children with Kawasaki disease. Zhongguo Dang Dai Er Ke Za Zhi Chin J Contemp Pediatr 12(3):169–171

    CAS  Google Scholar 

  29. Mueller C, Breidthardt T, Laule-Kilian K, Christ M, Perruchoud AP (2007) The integration of BNP and NT-ProBNP into clinical medicine. Swiss Med Wkly 137(1–2):4–12

    CAS  PubMed  Google Scholar 

  30. Tang WHW (2007) B-type natriuretic peptide: a critical review. Congest Heart Fail Greenwich Conn 13(1):48–52

    Article  CAS  Google Scholar 

  31. Steiner J, Guglin M (2008) BNP or NTProBNP? A clinician’s perspective. Int J Cardiol 129(1):5–14

    Article  PubMed  Google Scholar 

  32. Iwashima S, Ishikawa T (2013) B-type natriuretic peptide and N-terminal ProBNP in the acute phase of Kawasaki disease. World J Pediatr WJP 9(3):239–244

    Article  CAS  PubMed  Google Scholar 

  33. Sato S, Kawashima H, Kashiwagi Y, Hoshika A (2013) Inflammatory cytokines as predictors of resistance to intravenous immunoglobulin therapy in Kawasaki disease patients. Int J Rheum Dis 16(2):168–172

    Article  CAS  PubMed  Google Scholar 

  34. Moran AM, Newburger JW, Sanders SP, Parness IA, Spevak PJ, Burns JC et al (2000) Abnormal myocardial mechanics in Kawasaki disease: rapid response to gamma-globulin. Am Heart J 139(2 Pt 1):217–223

    CAS  PubMed  Google Scholar 

  35. Sato YZ, Molkara DP, Daniels LB, Tremoulet AH, Shimizu C, Kanegaye JT et al (2013) Cardiovascular biomarkers in acute Kawasaki disease. Int J Cardiol 164(1):58–63

    Article  PubMed  PubMed Central  Google Scholar 

  36. Cho SY, Kim Y, Cha S-H, Suh J-T, Han MY, Lee HJ (2011) Adjuvant laboratory marker of Kawasaki disease; NT-ProBNP or hs-CRP? Ann Clin Lab Sci 41(4):360–363

    CAS  PubMed  Google Scholar 

  37. McNeal-Davidson A, Fournier A, Spigelblatt L, Saint-Cyr C, Mir TS, Nir A et al (2012) Value of amino-terminal pro B-natriuretic peptide in diagnosing Kawasaki disease. Pediatr Int Off J Jpn Pediatr Soc 54(5):627–633

    Article  CAS  Google Scholar 

  38. Sleeper LA, Minich LL, McCrindle BM, Li JS, Mason W, Colan SD et al (2011) Evaluation of Kawasaki disease risk-scoring systems for intravenous immunoglobulin resistance. J Pediatr 158(5):831–835

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Allergy-Immunology, Advanced Pediatrics Centre, Postgraduate Institute of Medical, Education and Research (PGIMER), Chandigarh, India

    Mounika Reddy, Surjit Singh, Amit Rawat, Avinash Sharma & Deepti Suri

  2. Department of Cardiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

    Manoj Kumar Rohit

Authors
  1. Mounika Reddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Surjit Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amit Rawat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Avinash Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Deepti Suri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Manoj Kumar Rohit
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Surjit Singh.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Reddy, M., Singh, S., Rawat, A. et al. Pro-brain natriuretic peptide (ProBNP) levels in North Indian children with Kawasaki disease. Rheumatol Int 36, 551–559 (2016). https://doi.org/10.1007/s00296-016-3430-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-016-3430-6

Keywords

Search

Navigation