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Dot plots of white blood cells (a), neutrophil percentage (b), platelet count (c), erythrocyte sedimentation rate (d), C-reactive protein level (e), and serum albumin level (f) in patients with complete Kawasaki disease (cKD), incomplete KD (iKD), and febrile illness (control). ∗P<0.05. ∗∗, @@, and ##P<0.01. NS: not significant.
Source publication
N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was recently reported as a biomarker for diagnosing Kawasaki disease (KD). The basal NT-proBNP level, however, gradually decreases with age. We investigated the usefulness of an age-stratified cutoff value of NT-proBNP for diagnosing KD. All the patients enrolled in this study visited C...
Similar publications
This corrects the article on p. 755 in vol. 49, PMID: 31074226.
Objectives:
To determine the prevalence of subsequent stenotic lesions based on the maximum diameter of the largest coronary artery aneurysm in patients with Kawasaki disease and the threshold value of coronary artery diameter associated with risk of developing stenotic lesion.
Study design:
There were 214 patients (160 males) who had at least 1...
The pandemic of COVID-19 caused by Severe Acute
Respiratory Syndrome Coronavirus-2 (SARS
CoV-2) has led to a global threat infecting
individuals of all ages. It has resulted in more
than 176 million confirmed cases and over three
million deaths worldwide (1). In Sri Lanka, there
are more than 175,000 diagnosed COVID-19 cases
and still in the r...
Several studies demonstrated that COVID-19 in children is a relatively mild disease. However, recently a more serious condition characterized by systemic inflammation with clinical or microbiological evidence of exposure to SARS-CoV-2 has been described. This syndrome is now known as either “Pediatric Inflammatory Multisystem Syndrome temporally re...
Background
There is growing evidence of Multisystem Inflammatory Syndrome in Children (MIS-C) resembling Kawasaki disease in children infected with SARS-CoV-2. The review was undertaken to evaluate the case definition, the spectrum of clinical presentations and current management practices in children with COVID-19 presenting with or without MIS-C....
Citations
... Previous studies showed that proBNP increases markedly in incomplete KD and is useful to T A B L E 5 Echocardiogram data for PICU-admitted and non-admitted patients during a subacute follow-up evaluate the progression of KSS. 32 Since proBNP determination was not available in all the participating centers, we could not directly address its predictive value for PICU admission. However, the data suggest that, together with variables that assess myocardial function, it could alert to the need for IVIG/steroid treatment and admission to the PICU. ...
Background:
The impact of the Pediatric Inflammatory Multisystem Syndrome temporally-associated with SARS-CoV-2 (PIMS-TS) in low and middle-income countries remains poorly understood. Our aim was to understand the characteristics and outcomes of PIMS-TS in Argentina.
Methods:
This observational, prospective and retrospective multicenter study, enrolled patients younger than 18 years-old showing PIMS-TS, Kawasaki disease (KD) or Kawasaki shock syndrome (KSS) manifestations between March 2020 and May 2021. Patients were followed-up until hospital discharge or death (which occurred in one case). The primary outcome was PICU admission. Multiple logistic regression was used to identify variables predicting PICU admission.
Results:
Eighty-one percent, 82% and 14% of the 176 enrolled patients fulfilled the suspect case criteria for PIMS-TS, KD, and KSS, respectively. Temporal association with SARS-CoV-2 was confirmed in 85% of the patients and 38% were admitted to PICU. The more common clinical manifestations were fever, abdominal pain, rash and conjunctival injection. Lymphopenia was more common among PICU-admitted patients (87% versus 51%, p<0.0001), who also showed a lower platelet count and higher plasmatic levels of inflammatory and cardiac markers. Mitral valve insufficiency, left ventricular wall motion alterations, pericardial effusion and coronary arteries alterations were observed in 30%, 30%, 19.8%, 18.6% of the patients, respectively. Days to initiation of treatment, rash, lymphopenia, and low platelet count did significant independent contributions to PICU admission.
Conclusion:
Rates of severe outcomes of PIMS-TS in the present study agreed with those observed in high-income countries. Together with other published studies, this work helps to better understand this novel clinical entity.
... Notably, its secretion is also influenced by the inflammatory response [20,21]. NT-proBNP is increasingly used as a biomarker in pediatric conditions that combine myocardial stress and inflammatory diseases, such as sepsis or Kawasaki disease [22][23][24]. Therefore, it is not surprising that NT-proBNP levels are markedly raised in almost all patients with MIS-C, where the proposed mechanism for the cardiovascular dysfunction is myocardial inflammation related to systemic inflammation with a cytokine storm [4,8,11,25,26]. ...
Background:
Multisystem inflammatory syndrome in children (MIS-C) has emerged as a new disease associated with COVID-19 that presents in acute critically ill children with acute cardiovascular dysfunction.
Aim:
To determine whether the age-adjusted N-terminal pro-brain natriuretic peptide (NT-proBNP) value (Z-log-NT-proBNP) is associated with severe MIS-C and myocardial dysfunction.
Methods:
A retrospective study was conducted which included children with MIS-C managed at our institution between April 1, 2020, and February 28, 2022. We divided the population into groups depending on severity based on pediatric intensive care unit (PICU) admission. We compared Z-log-NT-proBNP values across these groups and analyzed Z-log-NT-proBNP dynamics during the one-month follow-up.
Results:
We included 17 participants [median age 3 (2-9) years] and seven (41%) required PICU admission. All (100%) of these cases presented very high (Z-log > 4) levels of NT-proBNP at the time of admission compared to only 5 (50%) patients with non-severe MIS-C (P = 0.025). NT-proBNP was significantly correlated with high-sensitive Troponin I levels (P = 0.045), Ross modified score (P = 0.003) and left ventricle ejection fraction (P = 0.021).
Conclusion:
Raised NT-proBNP, specifically very high values (Z-log-NT-proBNP > 4) could help in the early identification of MIS-C patients with myocardial dysfunction requiring inotropic support and PICU admission.
... N-terminal prohormone Brain Natriuretic Peptide (NT-proBNP) is the most studied marker in KD due to its usefulness in diagnosis and prognostic value [123]. Raised NT-proBNP correlates with the manifestation of coronary artery aneurysm and can predict the presence of IVIG resistance in KD patients [123,124]. Furthermore, the usage of NT-proBNP as a diagnostic marker was also substantiated by multiple studies and meta-analyses [125][126][127][128]. Although NT-proBNP is non-specific andlimiting the diagnostic usefulness of this marker for KD, the usefulness warrants future studies to investigate the value of NT-proBNP in either diagnostic, prognostic, or treatment algorithms with the combination of other clinical criteria and laboratory findings [123]. ...
Kawasaki disease (KD) has shown a marked increase in trend over the globe, especially within the last two decades. Kawasaki disease is often seen in the paediatric population below five years old, while it is rare for those who are beyond that age. Up to this date, no exact causes has been identified although KD was found more than half a century ago. The underlying pathogenesis of the disease is still unelucidated, and researchers are trying to unlock the mystery of KD. To further complicate the diagnosis and the prompt management, a specific biomarker for the diagnosis of KD is yet to be discovered, making it hard to differentiate between KD and other diseases with a similar presentation. Nonetheless, since its discovery, clinicians and scientists alike had known more about the different clinical aspects of typical KD. Thus, this article intends to revisit and review the various clinical manifestations and laboratory characteristics of KD in order to guide the diagnosis of KD.
... It is important to note that normal values of NT-proBNP change according to age. Nir et al. reported 1000 pg/mL of NT-proBNP as the 97.5 th percentile for normal children between 1 and 12 months (median 141 and range 5-1121) [25], and Lee et al. reported 669 ± 660 (mean, SD) in control patients younger than 6 months with febrile episodes different from KD [26]. IVIG resistance has been described more often in KD patients below 6 months of age [11,14], Mastrangelo et al. reported 21% of non-response to the first dose of IVIG in this population. ...
A retrospective study that compared children younger than 6 months versus older children of a Spanish cohort of patients diagnosed with Kawasaki disease between 2011 and 2016 (Kawa-Race study). From the 598 patients recruited, 42 patients were younger than 6 months (7%) and presented more frequently with an incomplete diagnosis of Kawasaki disease (52.4 vs 27.9%, p = 0.001). Cardiac abnormalities detected by echocardiography were more common in younger patients (52.4 vs 30%, p = 0.002). These younger patients presented with a higher proportion of coronary aneurysms as well (19 vs 8.6%, p < 0.001). Shock at diagnosis (9.5 vs 1.9%, p = 0.016) and admission to intensive care units (17.7 vs 4.1%, p = 0.003) were more frequent in patients younger than 6 months. There were no statistically significant differences in relation to infections, non-response to IVIG, or mid- or long-term outcomes.Conclusion: Data of the Spanish cohort are consistent with other American and Asian studies, although Spanish children younger than 6 months had a lower rate of non-response to IVIG and better clinical outcomes. A high index of suspicion should be considered for this population due to a higher risk of coronary abnormalities, presentation of shock, and admission to the intensive care unit.
What is Known:
•Children below 6 months of age with Kawasaki disease (KD) have different features compared to older.
•Younger patients usually have an incomplete form of KD and coronary artery abnormalities.
What is New:
•Younger than 6 months with KD presented with shock and required admission to PICU more frequently compared to older.
•Infections play a similar role in KD despite the age of the patients.
... It has also been attempted to relate this molecule to the risk of AC lesions [12]. The latest meta-analysis published in the literature by Zheng et al. in 2020 established a causal relationship with values greater than 2500 pg/ml and CA with an area under the curve (AUC) of 0.858, with a sensitivity (S) and specificity (E) of 0.84 and 0.71, respectively [13]. ...
Kawasaki disease is the most common heart disease acquired during childhood in the world. Nowadays none of these criteria are specific or pathognomonic for Kawasaki disease; therefore, due to the high prevalence of febrile diseases in childhood, it leads to a significant delay in the diagnosis with the consequent increase in the incidence morbidity and mortality. Is it possible to diagnose incomplete KD earlier? Can the new biomarkers help to predict resistance to classical treatment and/or coronary involvement? Is it possible to choose a specific treatment?
... Finally, 12 studies with 2173 KD children and 1909 non-KD children were included in the current meta-analysis. [21][22][23][24][25][26][27][28][29][30][31][32] Figure 1 is a flowchart depicting the study selection process. Table 1 summarises the characteristics of eligible studies. ...
... Six of the eligible studies determined circulating NT-proBNP with Roche electrochemiluminescence immunoassay. [21][22][23][24]26,31 Only two studies reported that the patients were enrolled consecutively. 29,30 Four studies adopted ...
... Eight of the eligible studies adopted a threshold between 100 and 300 pg/mL. [21][22][23]26,27,29,31,32 The eligible studies' sensitivity ranged from 0.69 to 1.00, and the specificity ranged from 0.63 to 0.98. Figure 2 is a forest plot depicting the sensitivity and specificity of all eligible studies. ...
Objective
This study aimed to investigate the diagnostic accuracy of N-terminal pro-brain natriuretic peptide (NT-proBNP) for Kawasaki Disease (KD).
Methods
We searched PubMed, Web of Science, EMBASE to identify the eligible studies investigating the diagnostic accuracy NT-proBNP for KD. The revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2) was used to evaluate eligible studies' quality. A meta-analysis was performed with the bivariate model and summary receiver operating characteristic (sROC) curve. We also performed subgroup, publication bias, and sensitivity analyses.
Results
We included 12 studies with 2173 Kawasaki Diseases and 1909 control. The pooled sensitivity and specificity of eligible studies were 0.80 (95%CI: 0.72 – 0.86) and 0.81 (95%CI: 0.73 – 0.88), respectively. The area under sROC curve was 0.88 (95%CI: 0.84 – 0.90). Patient selection bias and partial verification bias were the major design weakness of the eligible studies. Sensitivity analysis revealed that the results of this meta-analysis were robust. Subgroup analysis revealed that study design, NT-proBNP assay, and participants' body temperature were not the source of heterogeneity across all eligible studies. No publication bias was observed.
Conclusion
NT-proBNP has moderate diagnostic accuracy for KD. It cannot be used in ruling in or ruling out KD when used alone.
... In recent years, developments in molecular biology and clinical medicine techniques have made it possible to discover biomarkers as a powerful instrument for stratifying the risk and predicting the prognosis of cardiovascular diseases (21). Myocardial cell stress-related biomarkers are raised in most patients suffering from acute KD; NT-proBNP is associated with inflammation, while oxidative stress markers and echocardiographic results indicate diastolic dysfunction (22). Myocardial cells release NT-proBNP against the inflammatory cytokines and ventricular dilatation. ...
... NT-proBNP may be a more useful biomarker for diagnosing KD compared with the highly sensitive CRP (19). The mean NT-proBNP levels in patients with complete and incomplete KD was considerably higher than that of age-matched patients with simple fever (22). In addition, the mean NT-proBNP levels in patients with complete KD was higher than that of patients with incomplete KD (23,24). ...
The utility of color Doppler echocardiography in the diagnosis and follow-up of Kawasaki disease (KD) with coronary artery lesions (CAL) was analyzed, and the clinical parameters associated with the disease were examined. The general data, the color Doppler echocardiography data and the biochemical indexes from 102 children with KD were analyzed. The patients were divided into a CAL group and a non-coronary artery lesion (NCAL) group based on the presence or absence of CAL. The risk factors for CAL in KD were screened by univariate and multivariate analyses. Among the 102 cases, CAL complications were identified in 47 cases (46.08%). Compared with the NCAL group, the CAL group showed significantly higher incidences of fever duration, increased levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), C-reactive protein (CRP), intravenous immunoglobulin resistance, erythrocyte sedimentation rate (ESR), platelets, alanine aminotransferase and aspartate aminotransferase, and significantly lower serum albumin levels (P<0.05). According to the multivariate analysis, fever duration [odds ratio (OR)=2.014], NT-proBNP (OR=3.004), cTnI level (OR=2.638), ESR (OR=1.461) and CRP elevation (OR=1.094) were predictors of CAL in KD. During convalescence, the left and right coronary artery diameters in the CAL group significantly decreased (P<0.05). Color Doppler echocardiography can observe the condition of coronary artery disease in patients with KD in real time and predicts its outcomes, which may be helpful for early diagnosis and long-term follow-up. Fever duration, cTnI, NT-proBNP and ESR levels were correlated with coronary artery diameter, of which the comprehensive use may be more accurate in determining the occurrence of CAL in KD.
... sensitivity, and specificity of 80% and 85%, respectively) (45). Moreover, the control group of other studies comprised febrile patients due to a variety of known or unknown causes (38,(40)(41)(42). ...
... NT-proBNP is considerably high in newborns, drops a few days after birth, and continues to further decrease with lower rate thereafter throughout early childhood (43,44). Hence, in a few studies, the investigators tried to find age-based cut-off points and z values (40,45). In this regard, Lee et al. evaluated the level of 214 KD patients fulfilling complete criteria (complete KD) and 129 patients with incomplete KD and compared it with 62 febrile patients. ...
... They reported an overall NT-proBNP cut-off point of 289 pg/mL (AUC=0.774). Furthermore, they suggested agedependent NT-proBNP cut-off points of 762 and 762 pg/mL for complete and incomplete KD, respectively in under six months of age, 310 and 310 pg/mL in 6-12 months, 326 and 326 pg/mL in 12-24 months, and 208 and 137 pg/mL in more than 24 months (40). Another study by Shiraishi et al. indicated relatively higher age-based cut-off points for NTproBNP, including 1,000 pg/ml for 1-11 months of age, 900 pg/ml for 1 year, 800 pg/ml for 2 years, 700 pg/ml for 3 years, 600 pg/ml for 4 and 5 years, 500 pg/ml for 6 and 7 years, 400 pg/ml for 8 and 9 years, and 300 pg/ml for 10-15 years of age (45). ...
Kawasaki disease (KD) is characterized as the leading cause of acquired cardiac disease in children. Accurate and timely diagnosis of KD is of high importance for preventing its cardiac complications. However, diagnosis merely based on clinical findings has a number of challenges and limitations. Therefore, researchers are investigating to find more objective and accurate diagnostic modalities. Cardiac biomarkers, particularly N-terminal pro b-type natriuretic peptide (NT-proBNP), are the most acknowledged diagnostic biomarkers in this regard. Accordingly, this paper reviewed some recent and related studies so as to evaluate the advantages and disadvantages of each cardiac biomarker.
... After these meta-analyses, seven subsequent retrospective studies have compared the levels of NT-proBNP between KD and febrile controls, and have investigated the diagnostic accuracy of NT-proBNP for KD [96,[115][116][117][118][119][120]. These studies included a total of 1513 patients with a mean age of patients ranging from 2.1 to 45 months. ...
Kawasaki disease (KD) is a systemic childhood vasculitis with peculiar tropism for the heart. Coronary artery aneurysms are the primary cause of morbidity and mortality in these patients. The timely administration of gammaglobulin decreases the risk for development of coronary artery aneurysms, highlighting the importance of early KD recognition. However, the most significant dilemma in the management of KD is the diagnosis itself. In this article, we review the recent literature focusing on the diagnostic utility of N-terminal probrain natriuretic peptide as a biomarker for diagnosis of KD. The main conclusion is that N-terminal probrain natriuretic peptide is an useful biomarker for KD diagnostic that represents a valuable addition to the current diagnostic workup of patients with suspected KD, increasing the diagnostic accuracy.
... They found that an increase in CRP was not an independent marker but, instead, a confounder on logistic regression analysis. On the contrary, NT-proBNP itself was a robust and independent diagnostic marker of KD and useful in distinguishing it from uncomplicated febrile illness [124]. Ye et al. prospectively compared different laboratory parameters between KD patients and KD-like febrile patients. ...
... According to the results of Nir et al., the upper limit for age (95th centile) is 646 pg/ml for infants between 1 month and 1 year, 413 pg/ml for children between 1 and 2 years, 289 pg/ml for those between 2 and 6 years, and 157 pg/ml for those more than 6 years [127]. Also, plasmatic NT-proBNP level of patients with KD has been demonstrated to be inversely correlated with the age by several authors [91,94,124,[128][129][130]. Furthermore, the diagnostic accuracy of an age-stratified NT-proBNP level approach seems to be good. ...
... The age-specific AUC value and NT-proBNP level with maximal Youden index were 0.796 and 679.4 in the 1-12 months group, 0.843 and 385.3 in the 13-24 months group, and 0.763 and 244.7 pg/ml in the 25 months to 6 years group, respectively. Lee et al. divided 343 KD patients into subgroups according to patient age (<6, 6-12, 12-24 and >24 months), and also the younger children presented higher NT-proBNP levels (mean NT-proBNP of 3404, 2241, 1332 and 1583 pg/ml, respectively) [124]. The cutoff value in the total KD patient group of all ages was 289 pg/ml, with 71.7% sensitivity and 71.9% specificity, AUC = 0.774. ...
Kawasaki disease (KD) is a systemic childhood vasculitis with peculiar tropism for the heart. Coronary artery aneurysms are the primary cause of morbidity and mortality in these patients. The timely administration of gammaglobulin decreases the risk for development of coronary artery aneurysms, highlighting the importance of early KD recognition. However, the most significant dilemma in the management of KD is the diagnosis itself. In this article, we review the recent literature focusing on the diagnostic utility of N-terminal probrain natriuretic peptide as a biomarker for diagnosis of KD. The main conclusion is that N-terminal probrain natriuretic peptide is an useful biomarker for KD diagnostic that represents a valuable addition to the current diagnostic workup of patients with suspected KD, increasing the diagnostic accuracy.
