Abstract
Background
Intravenous immunoglobulin (IVIG) has been the mainstay of treatment for Kawasaki disease (KD) over the past decades. However, 10–20% of KD patients are resistant to IVIG treatment which puts those patients at high risk of coronary artery lesions (CALs). Therefore, it is important to predict whether patients will be resistant to IVIG before the treatment. This study aimed to investigate the risk factors for IVIG non-responsive patients with KD.
Methods
This study enrolled patients diagnosed with KD and divided them into two groups, IVIG responders and IVIG non-responders. We compared the differences in demographics and clinical data between the two groups. Differences among the groups were analyzed by ANOVA and Chi-square analysis. Predictors of IVIG resistance were determined by multiple logistic regression analysis and receiver operating characteristic (ROC) curve analysis.
Results
In total, 907 KD patients were reviewed, with 841 IVIG responders and 66 IVIG non-responders. Patients in IVIG responders were younger than IVIG non-responders. The length of hospitalization of the IVIG non-responders was significantly longer than IVIG responders. The neutrophils%, C-reaction protein (CRP), and CRP/albumin ratio in IVIG responders were significantly lower than in IVIG non-responders (P < 0.05). The lymphocyte% and Albumin in IVIG responders were significantly higher than in IVIG non-responders. Multivariable logistic regression analysis demonstrated that albumin (OR = 0.881, 95% CI, 0.781 to 0.994, p-value = 0.039) was an independent risk factor for predicting IVIG resistance. The area under the ROC curve was 0.644, with a cut-off of ≤ 33.4 g/L determined by Youden’s index. The sensitivity and specificity in predicting IVIG resistance were 40.91% and 83.47%, respectively.
Conclusion
Albumin can serve as a potential predicting marker for IVIG resistance in KD. A lower albumin level may be useful for identifying KD patients with a high risk of IVIG resistance to guide further therapy strategies.
Similar content being viewed by others
![](https://media.springernature.com/w215h120/springer-static/image/art%3Aplaceholder%2Fimages/placeholder-figure-springernature.png)
Background
Kawasaki disease (KD) is an acute self-limiting inflammatory disorder associated with vasculitis, affecting predominantly medium-sized arteries, particularly the coronary arteries [1]. KD occurs primarily in children < 5 years of age and is now recognized as the most common cause of acquired heart disease in children in developed countries [2]. Intravenous immunoglobulin (IVIG) and aspirin have been established as the first-line therapy for KD to control inflammation and reduce the risk of coronary artery lesions (CALs) [3]. However, approximately 10–20% of KD patients who do not respond to the initial IVIG therapy are termed IVIG resistant [4]. IVIG resistance puts patients with KD at a higher risk for CALs and increases the treatment burden. Therefore, early prediction of initial IVIG resistance is vital in KD as those patients might benefit from an early-intensified therapy.
The systematic inflammatory response plays a critical role in the progression of KD, although the etiology of KD remains unknown [5]. Albumin (Alb), traditionally regarded as a marker of nutritional status [6], is a commonly used negative acute phase reactant. The albumin level is correlated with the severity of the acute inflammation, and hypoalbuminemia was commonly observed in KD patients during the acute phase [7]. Moreover, the C-reactive protein (CRP) to albumin (CRP/Alb, CAR) ratio has been considered a novel predicting marker for CALs formation and IVIG resistance in KD [8]. Thus, in this study, we aim to evaluate the predictive value of CPR, albumin, and CRP/ALB ratio for IVIG resistance in KD patients.
Methods
The Chengdu Women’s and Children’s Central Hospital Ethics Committee approved the study protocol (Approval No. B202213) and waived informed consent requirements. All methods were carried out following the Declaration of Helsinki.
Study design, setting, and study subjects
This was a retrospective cohort study. We retrospectively reviewed the clinical records of patients with KD hospitalized at Chengdu Women’s and Children’s Central Hospital from January 2018 to December 2020. All the KD patients (including complete and incomplete) were diagnosed according to the 2017 American Heart Association (AHA) guideline [1] and were confirmed by two experienced pediatricians. The inclusion criteria for study subjects were as follows: (1) patients were <18 years old; (2) patients of initial onset of KD; (3) patients received standard treatment with 2 g/kg of IVIG of single infusion within 10 days from fever onset. Exclusion criteria were as follows: (1) recurrent KD; (2) patients who had a serious infection, immune diseases, metabolic disease, hematological disease, or cardiovascular system diseases; (3) patients who had received IVIG within 6 months in other medical facilities; (4) patients who did not receive IVIG or initial IVIG dose was < 2 g/kg; (5) patients with malnutrition and nutritional imbalance; (6) incomplete clinical or laboratory information.
Complete KD was diagnosed in children with a fever and had four or more of the following major symptoms: (I) polymorphous exanthema, (II) erythema and cracking of lips, strawberry tongue, and/or erythema of oral and pharyngeal mucosa, (III) changes of the peripheral extremities, (IV) bilateral conjunctival congestion, and (V) unilateral cervical lymphadenopathy. Incomplete KD was defined as a child with a fever with < 4 major symptoms and compatible laboratory or echocardiographic findings [1].
Treatment regimen
According to our institutional treatment protocol, all KD patients were treated with oral aspirin (30-50 mg/kg/d) and IVIG (2 g/kg) within 10 days from fever onset. The dose of aspirin was decreased to 3–5 mg/kg/day after defervesce for 48 h. The second IVIG dose (2 g/kg) was administered if patients had an initial IVIG resistance. For patients with repeated IVIG resistance, intravenous methylprednisolone (30 mg/kg/dose) was given for 3 consecutive days. No patients received additional therapy such as plasma exchange, infliximab, or cytotoxic agents.
Initial IVIG resistance was defined as those with persistent fever for at least 36 h after completion of initial IVIG infusion [1]. Repeated IVIG resistance was defined as recurrent or persistent fever for at least 36 h after the second IVIG treatment. The patients who met the inclusion criteria were classified into two groups according to whether they were responsive or non-responsive to initial IVIG: IVIG responders and IVIG non-responders.
Data collection
Clinical and laboratory data were collected through medical record review. Clinical data such as age, sex, and time of the first dose of IVIG were collected. Laboratory data on admission pre-IVIG treatment was collected, including CRP, hemoglobin (Hb), white blood count (WBC), platelet count (PLT), percentage of neutrophils (N%), lymphocytes, serum alanine aminotransferase (ALT), serum aspartate aminotransaminase (AST), albumin. All blood samples were collected before the initial IVIG infusion. The CRP to albumin ratio (CAR) was calculated by dividing CRP by albumin collected before the initial IVIG treatment. We would use the highest level of CRP and the lowest level of albumin for the analysis of CAR if there were more than one result of CRP or albumin before the initial IVIG infusion.
Statistical analyses
The normality of distribution of variables was checked using the Kolmogorov-Smirnov test. Continuous variables were expressed as mean ± standard deviations or median and IQR (25th, 75th percentile) if non-normally distributed. Categorical variables were expressed by presenting the frequency and proportion in each category. The Chi-square or Fisher’s exact test was applied to compare categorical variables. Student’s t-test or Mann–Whitney U-test was used for continuous variables. We performed multivariate logistic regression analysis to identify the independent predictors of IVIG resistance. The receiver operating characteristic curve (ROC) was analyzed to assess the predictive accuracy of independent predictors for IVIG resistance. We also performed subgroup analysis by dividing the KD patients into complete and incomplete KD. Data were analyzed using IBM SPSS Statistics 25.0 (SPSS, Chicago, IL, USA). For all analyses, P < 0.05 was considered to be statistically significant.
Results
Study selection
A total of 1097 children were diagnosed with KD during the study period. Seven received initial IVIG dose < 2 g/kg, 32 were recurrent KD, 101 had severe infection diseases, and 50 had incomplete clinical or laboratory data. After the exclusion, 907 KD patients who met the inclusion criteria were enrolled in this study (Fig. 1), including 841 IVIG responders and 66 IVIG non-responders.
Characteristics of KD Patient
Table 1 shows the basic demographics and laboratory characteristics of the IVIG responders and non-responders groups. There were no significant differences in gender, diagnosis, WBC, HB, ALT, and AST. A slight difference (P = 0.042) was observed in PLT between the two groups. In addition, IVIG non-responders group had a longer length of hospitalization and older age. Compared with the IVIG responders group, the N%, CRP, and CRP/Alb were significantly higher in patients with IVIG resistance. On the contrary, lymph (%) and albumin were significantly lower in patients with IVIG resistance (Supplementary file, Appendix S1).
Characteristics of complete and incomplete KD patients
There were 842 complete KD patients, with a median age of 23 (13, 38.5) in IVIG responders and 32.5 (20, 55) months in IVIG non-responders. Patients in IVIG responders were younger than IVIG non-responders (P<0.01). The ratio of males to females was 1.44:1. Among all the complete KD patients, 780 were classified as IVIG responders, and 62 were IVIG non-responders. The length of hospitalization of the IVIG non-responders was significantly longer than IVIG responders. The N%, CRP, and CRP/Alb ratio in IVIG responders were significantly lower than in IVIG non-responders (P < 0.05). The lymphocyte% and albumin in IVIG responders were significantly higher than in IVIG non-responders. There were no statistical differences in PLT, WBC, HB, ALT, and AST among the two groups. Detailed information on the characteristics of complete KD patients can be seen in the Supplementary file, Appendix S2. There were 65 incomplete KD patients, with 61 IVIG responders and 4 IVIG non-responders. There were no statistical differences between the IVIG responders and IVIG non-responders in the incomplete KD, except the HB (Supplementary file, Appendix S3).
Multivariate logistic analysis and ROC curve for predicting IVIG-resistance
Statistically significant variables were enrolled in the multivariate logistic regression from the univariate analysis. It was identified that lower albumin was an independent risk factor for IVIG resistance (Table 2). The area under the ROC curve (AUC) was 0.644, with a cut-off of ≤ 33.4 g/L determined by Youden’s index. The sensitivity and specificity in predicting IVIG-resistance were 40.91% and 83.47%, respectively (Fig. 2). The multivariate logistic analysis in complete KD was shown in the Supplementary file, Appendix S4. No significant differences were found using multivariable logistic regression analysis among the laboratory parameters that had revealed statistical differences in complete KD.
Discussion
In the present study, the authors aimed to investigate the predictive value of laboratory parameters for initial IVIG resistance in KD patients. In the large retrospective cohort of 907 patients from southwestern China, univariable logistic regression analysis showed that N%, CRP, and CRP/Alb were significantly higher in the IVIG non-responders group than in the IVIG responders group. In addition, the lymph (%) and albumin were significantly lower in patients with IVIG resistance. Multivariable logistic regression analysis revealed that only lower albumin (≤ 33.4 g/L) before IVIG treatment was an independent risk factor (OR = 0.881, 95% CI, 0.781 to 0.994, p-value = 0.039) for initial IVIG resistance in KD patients. The AUC of albumin for predicting IVIG resistance in KD was 0.644, with a sensitivity and specificity value of 40.91% and 83.47%, respectively. Our study suggests that albumin is an independent predictor for IVIG resistance and may be useful in predicting initial IVIG resistance in KD patients.
Different clinical guidelines recommend IVIG as the first-line therapy to treat KD [1, 9]. Standard treatment with IVIG and aspirin significantly reduces the prevalence of CALs [10]. Nevertheless, about 10–20% of KD patients were IVIG-resistant and at a higher risk of developing cardiac complications [1]. Therefore, early prediction of IVIG resistance is one pivotal topic of interest and research hotspots in KD since those KD patients with IVIG resistance might improve an early-intensified therapy [11]. There are several Japanese (e.g., Harada score [12], Egami score [13], Kobayashi score [14]) or North American risk-scoring systems [15] for predicting IVIG resistance. However, these scoring systems are considered to be complicated and showed lower prediction effectiveness in non-Japanese populations [16,17,18,19]. Notably, the incidence of IVIG resistance in the present study was 7.28% (66/907), which was lower than the proportions reported in previous studies (10-20%) [20]. Accumulating evidence has found the incidence of IVIG resistance seems to be lower in China than in other countries [21,22,23].
The IVIG non-responders had a longer hospitalization and older age than the IVIG responders. The longer length of hospitalization may be due to the requirement of additional IVIG infusion or adjunctive therapies in IVIG non-responders. It is worth noting that patients in IVIG non-responders group are significantly older (mean age = 32.5 months) than IVIG-responders. Previous investigations revealed that ages under 1 year old [24, 25] or under 6 months [16] were risk factors for IVIG resistance. But a recent study [26] also reported older age (mean age = 27.6 months) was a risk factor for IVIG resistance. There are reasons to speculate that both older and younger age (e.g., ≤ 12 months) are risk factors for IVIG resistance. Furthermore, IVIG non-responders group had a higher level of N%, CRP, and CRP/Alb, which was consistent with previous studies [27,28,29]. The present data indicate more severe inflammation in KD patients with IVIG resistance during the acute phase. On the contrary, lymph (%) and albumin were significantly lower in patients with IVIG resistance.
Albumin was an independent predictor for IVIG resistance in this study. The present results were in line with previous studies, which reported similar findings [16, 22, 30]. Serum albumin, traditionally regarded as a maker of nutritional status, is also increasingly considered the most critical negative acute-phase protein [6]. Catabolism of albumin is directly correlated with the severity of acute inflammation [7]. Vascular leakage was supposed to be a key feature of KD pathophysiology, leading to hypoalbuminemia [7]. The vascular endothelial growth factor (VEGF) level can reflect the severity of vascular leakage. Elevation of Serum VEGF concentration was correlated with low serum albumin in KD patients [31].
However, albumin may not be suitable as a single predictor to accurately predict initial IVIG resistance in a clinical setting because of its low sensitivities (40.91%). The possible explanation is that albumin is related to the general inflammatory response but insufficient in reflecting an overall perspective of KD. Other factors, such as genetic, immune and IVIG metabolic, have not been considered. The genetic factor probably plays the basis of the differences in the individual responses to IVIG therapy. However, subgroup analysis showed albumin (OR = 1.012, 95% CI, 0.971 to 1.05, p-value = 0.513) was not an independent risk factor of IVIG resistance in complete KD. Thus, the results of subgroup analysis also partly explained that albumin might not be sufficiently reliable as a single indicator in predicting IVIG resistance. Meanwhile, a single inflammatory parameter may be easily influenced by other factors. Thus, a prediction model combined with various parameters may theoretically be more reliable and have the potential to be a powerful candidate marker to evaluate inflammatory status. Still, albumin is a cost-effective alternative that may provide additional information for IVIG resistance prediction in KD patients considering it is routinely measured in clinical practice as part of the complete blood count.
Limitations
The present study was a retrospective study performed in a single hospital, which means potential selection or information bias may exist. Second, all participants were Chinese, which limits the generalizability of the results. Hence, further multicenter prospective studies are needed to verify the present results.
Conclusions
KD patients with IVIG resistance had a significantly lower level of albumin. Low albumin is identified as an independent risk factor of IVIG resistance in KD patients. Further multicenter prospective studies are required to confirm the present results.
Data Availability
The data used and/or analyzed during the current study are available within the manuscript.
Abbreviations
- IVIG:
-
Intravenous immunoglobulin
- KD:
-
Kawasaki disease
- CALs:
-
Coronary artery lesions
- ROC:
-
Receiver operating characteristic curve
- CRP:
-
C-reaction protein
- PLT:
-
Platelet
- WBC:
-
White blood cell
- Hb:
-
Hemoglobin
- Alb:
-
Albumin
- ALT:
-
Serum alanine aminotransferase
- AST:
-
Serum aspartate aminotransaminase
- AUC:
-
Area under curve
- AHA:
-
American Heart Association
- VEGF:
-
Vascular endothelial growth factor
References
McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, et al. Diagnosis, treatment, and long-term management of Kawasaki Disease: A Scientific Statement for Health Professionals from the American Heart Association. Circulation. 2017;135:e927–99.
Makino N, Nakamura Y, Yashiro M, Kosami K, Matsubara Y, Ae R, et al. Nationwide epidemiologic survey of Kawasaki disease in Japan, 2015–2016. Pediatr Int. 2019;61:397–403.
Broderick C, Kobayashi S, Suto M, Ito S, Kobayashi T. Intravenous immunoglobulin for the treatment of Kawasaki disease. Cochrane Database Syst Rev. 2023;1:Cd014884.
Newburger JW, Sleeper LA, McCrindle BW, Minich LL, Gersony W, Vetter VL, et al. Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease. N Engl J Med. 2007;356:663–75.
Kessel C, Koné-Paut I, Tellier S, Belot A, Masjosthusmann K, Wittkowski H, et al. An immunological Axis Involving Interleukin 1β and leucine-Rich-α2-Glycoprotein reflects therapeutic response of children with Kawasaki Disease: implications from the KAWAKINRA Trial. J Clin Immunol. 2022;42:1330–41.
Levitt DG, Levitt MD. Human serum albumin homeostasis: a new look at the roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum albumin measurements. Int J Gen Med. 2016;9:229–55.
Terai M, Honda T, Yasukawa K, Higashi K, Hamada H, Kohno Y. Prognostic impact of vascular leakage in acute Kawasaki disease. Circulation. 2003;108:325–30.
Tsai CM, Yu HR, Tang KS, Huang YH, Kuo HC. C-Reactive protein to albumin ratio for Predicting Coronary Artery Lesions and Intravenous Immunoglobulin Resistance in Kawasaki Disease. Front Pediatr. 2020;8:607631.
Marchesi A, Tarissi de Jacobis I, Rigante D, Rimini A, Malorni W, Corsello G, et al. Kawasaki disease: guidelines of the italian society of Pediatrics, part I - definition, epidemiology, etiopathogenesis, clinical expression and management of the acute phase. Ital J Pediatr. 2018;44:102.
Li Z, Cai J, Lu J, Wang M, Yang C, Zeng Z, et al. The therapeutic window of intravenous immunoglobulin (IVIG) and its correlation with clinical outcomes in Kawasaki disease: a systematic review and meta-analysis. Ital J Pediatr. 2023;49:45.
Xu B, Zhang Q, Du J, Shiraishi I, Jin H. Prediction of intravenous immunoglobulin-resistant Kawasaki disease: a research hotspot. Sci Bull (Beijing). 2023;68:121–4.
Harada K. Intravenous gamma-globulin treatment in Kawasaki disease. Acta Paediatr Jpn. 1991;33:805–10.
Egami K, Muta H, Ishii M, Suda K, Sugahara Y, Iemura M, et al. Prediction of resistance to intravenous immunoglobulin treatment in patients with Kawasaki disease. J Pediatr. 2006;149:237–40.
Kobayashi T, Inoue Y, Takeuchi K, Okada Y, Tamura K, Tomomasa T, et al. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation. 2006;113:2606–12.
Son MBF, Gauvreau K, Tremoulet AH, Lo M, Baker AL, de Ferranti S, et al. Risk Model Development and Validation for Prediction of Coronary Artery Aneurysms in Kawasaki Disease in a North American Population. J Am Heart Assoc. 2019;8:e011319.
Tang Y, Yan W, Sun L, Huang J, Qian W, Ding Y, et al. Prediction of intravenous immunoglobulin resistance in Kawasaki disease in an East China population. Clin Rheumatol. 2016;35:2771–6.
Sleeper LA, Minich LL, McCrindle BM, Li JS, Mason W, Colan SD, et al. Evaluation of Kawasaki disease risk-scoring systems for intravenous immunoglobulin resistance. J Pediatr. 2011;158:831–835e833.
Jakob A, von Kries R, Horstmann J, Hufnagel M, Stiller B, Berner R, et al. Failure to predict high-risk Kawasaki Disease Patients in a Population-based Study Cohort in Germany. Pediatr Infect Dis J. 2018;37:850–5.
Sánchez-Manubens J, Antón J, Bou R, Iglesias E, Calzada-Hernandez J, Borlan S, et al. Role of the Egami score to predict immunoglobulin resistance in Kawasaki disease among a western Mediterranean population. Rheumatol Int. 2016;36:905–10.
Okada K, Hara J, Maki I, Miki K, Matsuzaki K, Matsuoka T, et al. Pulse methylprednisolone with gammaglobulin as an initial treatment for acute Kawasaki disease. Eur J Pediatr. 2009;168:181–5.
Yang S, Song R, Zhang J, Li X, Li C. Predictive tool for intravenous immunoglobulin resistance of Kawasaki disease in Beijing. Arch Dis Child. 2019;104:262–7.
Xie T, Wang Y, Fu S, Wang W, Xie C, Zhang Y, et al. Predictors for intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease. Pediatr Rheumatol Online J. 2017;15:17.
Wei M, Huang M, Chen S, Huang G, Huang M, Qiu D, et al. A Multicenter Study of Intravenous Immunoglobulin non-response in Kawasaki Disease. Pediatr Cardiol. 2015;36:1166–72.
Qian W, Tang Y, Yan W, Sun L, Lv H. A comparison of efficacy of six prediction models for intravenous immunoglobulin resistance in Kawasaki disease. Ital J Pediatr. 2018;44:33.
Tan XH, Zhang XW, Wang XY, He XQ, Fan C, Lyu TW, et al. A new model for predicting intravenous immunoglobin-resistant Kawasaki disease in Chongqing: a retrospective study on 5277 patients. Sci Rep. 2019;9:1722.
Yan Y, Qiao L, Hua Y, Shao S, Zhang N, Wu M, et al. Predictive value of albumin-bilirubin grade for intravenous immunoglobulin resistance in a large cohort of patients with Kawasaki disease: a prospective study. Pediatr Rheumatol Online J. 2021;19:147.
Cai JH, Tang M, Zhang HX, Dan Luo E, Zhang R, Shuai SP et al. Therapeutic window of Intravenous Immunoglobulin (IVIG) and its correlation with IVIG-resistant in Kawasaki Disease: a retrospective study. J Pediatr (Rio J) 2022.
Shuai S, Zhang H, Zhang R, Tang M, Luo E, Yang Y et al. Prediction of coronary artery lesions based on C-reactive protein levels in children with Kawasaki Disease: a retrospective cohort study. J Pediatr (Rio J) 2023.
Liu X, Wang L, Zhou K, Shao S, Hua Y, Wu M, et al. Predictive value of C-reactive protein to albumin ratio as a biomarker for initial and repeated intravenous immunoglobulin resistance in a large cohort of Kawasaki disease patients: a prospective cohort study. Pediatr Rheumatol Online J. 2021;19:24.
Liu J, Huang Y, Chen C, Su D, Qin S, Pang Y. Risk factors for resistance to intravenous immunoglobulin treatment and coronary artery abnormalities in a chinese Pediatric Population with Kawasaki Disease: a retrospective cohort study. Front Pediatr. 2022;10:812644.
Yasukawa K, Terai M, Shulman ST, Toyozaki T, Yajima S, Kohno Y, et al. Systemic production of vascular endothelial growth factor and fms-like tyrosine kinase-1 receptor in acute Kawasaki disease. Circulation. 2002;105:766–9.
Acknowledgements
Not applicable.
Funding
This manuscript was supported by Sichuan Science & Technology Program (2023NSFSC0617) and Chengdu Medical Research Project [2022065].
Author information
Authors and Affiliations
Contributions
XY had full access to all of the data in the study and was responsible for the study conception. RZ, SS, HZ and JC drafted the manuscript. MT, SX, XL and NC had a role in collecting the data. YG did the statistical analysis. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
The Chengdu Women’s and Children’s Central Hospital Ethics Committee approved the study protocol (Approval No. B202213) and waived informed consent requirements. All methods were carried out following the Declaration of Helsinki.
Consent for publication
Not applicable.
Conflict of interest
The authors have no conflict of interest to declare.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Supplementary Material, Appendix S1
. Comparison of N%, L%, CRP, albumin and CRP/Alb between IVIG responders group and IVIG non-responders group. Appendix S2. Baseline characteristics of the complete KD patients. Appendix S3. Baseline characteristics of the incomplete KD patients. Appendix S4. Multivariable logistic regression analysis for predicting IVIG-resistance in complete KD patients
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
Zhang, R., Shuai, S., Zhang, H. et al. Predictive value of albumin for intravenous immunoglobulin resistance in a large cohort of Kawasaki disease patients. Ital J Pediatr 49, 78 (2023). https://doi.org/10.1186/s13052-023-01482-z
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s13052-023-01482-z