Pediatr Res. 2008 Feb;63(2):207-10.

Nephromegaly in children with Kawasaki disease: new supporting evidence

for diagnosis and its possible mechanism.

Huang HP, Lai YC, Tsai IJ, Chen SY, Cheng CH, Tsau YK.

Branch for Women and Children, Taipei City Hospital, Taipei 100, Taiwan.

Abstract

To measure the kidney size in children with Kawasaki disease (KD) and to delineate the condition of

nephromegaly, 20 children with KD were enrolled in our study. Kidney sizes were measured during acute stage in

these patients. Twenty healthy children and 15 febrile children served as healthy controls and fever controls,

respectively. To delineate the possible mechanism, we also evaluated kidney volume (KV) in 13 other patients

with KD during the acute phase and after the recovery phase as well as 26 healthy children. Plasma hepatocyte

growth factor (HGF) and transforming growth factor-beta1 (TGF-beta1) levels were determined for all children.

Kidney lengths and KV in patients with KD during the acute phase were significantly larger than those of healthy

children. There was no kidney enlargement in healthy controls and after the recovery phase. The ratio of patient

plasma HGF/TGF-beta1 during the acute phase and after the recovery phase correlated positively with the

degree of nephromegaly in all patients. These results confirm the presence of large kidneys in children with KD.

Our data also suggest that an elevated HGF/TGF-beta1 ratio may be responsible for the transient nephromegaly

in these children.

PMID: 18091351 [PubMed - indexed for MEDLINE]

Pediatr Nephrol. 2007 May;22(5):684-9. Epub 2006 Dec 7.

Renal scarring sequelae in childhood Kawasaki disease.

Wang JN, Chiou YY, Chiu NT, Chen MJ, Lee BF, Wu JM.

Institute of Clinical Medicine, National Cheng Kung University Medical College, Tainan, 70421, Taiwan.

Abstract

To assess renal inflammation and its sequelae in Kawasaki disease (KD) patients, we conducted a prospective

study in a university medical center setting in Taiwan. From June 2002 to January 2005, 50 children with KD were
enrolled, and after admission, all received technetium-99m dimercaptosuccinic acid scintigraphy single photon

emission computed tomography (DMSA renal SPECT), the results of which were used as the reference standard

for determining renal inflammation. Patients with renal inflammation underwent another DMSA renal SPECT more

than 6 months later to evaluate the sequelae. We found that 26 of the 50 patients (52%) had renal inflammatory

foci. There were no significant relationships between clinical or laboratory parameters and renal involvement in

KD, except the presence of coronary artery lesions [P<0.01; odds ratio (OR) 5.18; 95% confidence interval (CI)

1.52-17.65]. Although all patients were free of clinical symptoms, the 6-month follow-up DMSA renal SPECT

showed renal scarring in 11 of the 24 patients (46%). Patients with an initial abnormal renal ultrasound did predict

a greatly increased risk of scarring (P<0.05; OR 16.2; 95% CI 1.27-206.20). In conclusion, this study

demonstrated that the potential long-term clinical impact of KD is not limited to coronary artery lesion sequelae

but also includes renal scar formation.

PMID: 17151872 [PubMed - indexed for MEDLINE]

J Pediatr. 2010 May;156(5):792-7. Epub 2010 Feb 20.

Urinary cytokines and renal Doppler study in Kawasaki disease.

Wu JM, Chiou YY, Hung WP, Chiu NT, Chen MJ, Wang JN.

Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan.

Abstract

OBJECTIVE: To investigate whether renal vasculitis is the sole cause or merely a contributing cause of renal

inflammation in Kawasaki disease (KD).

STUDY DESIGN: This prospective study in a university medical center in Taiwan enrolled 24 children with KD

between June 2004 and November 2005. All patients underwent a technetium-99 m dimercaptosuccinic acid

scintigraphy single-photon emission computed tomography scan, the results of which were used to group the

patients with KD as with or without renal involvement. Urine samples underwent a cytokine analysis. Renal

Doppler ultrasonography was used to evaluate renal vasculitis by measuring the pulsatility index (PI) and

resistance index (RI).

RESULTS: Ten of the 24 patients (42%) with renal inflammatory foci were the study group; the remainder

composed the control group. Urinary interleukin (IL)-6 levels were significantly higher in the study group (496.7 +/-
310.9 vs 115.0 +/- 65.9 ng/g urinary creatinine; P < .01), as were PI values (1.85 +/- 0.70 vs 1.44 +/- 0.53; P < .

05). Urinary IL-6 levels and PI values were significantly (P < .05) correlated.

CONCLUSIONS: Increased urinary IL-6 and elevated renal Doppler measures suggest that immune-mediated

vasculitis is one of the mechanisms causing renal inflammation in KD.

PMID: 20171655 [PubMed - indexed for MEDLINE]

J Trop Pediatr. 2009 Feb;55(1):55-7. Epub 2008 Jul 31.

Atypical kawasaki disease presenting with symptoms from the genitourinary

system: an autopsy report.

Papadodima SA, Sakelliadis EI, Goutas ND, Vlachodimitropoulos DG, Spiliopoulou CA.

Department of Forensic Medicine & Toxicology, National & Kapodistrian University of Athens, Greece.

stpapd@gmail.com

Abstract

Symptoms from the genitourinary system are unusual in Kawasaki disease (KD). Renal involvement is even rarer

and it is confirmed by biopsy when the person is alive. We describe the case of an 11-year-old boy admitted to

the hospital complaining about prolonged fever (5 days) and hematuria. His urinalysis showed also pyuria,

proteinuria and urinary renal tubular epithelial cells concentrations. During the next days, the patient presented

limb edema. After almost 2 weeks of hospitalization the patient was transferred to the intensive care unit because

of melena and intense abdominal pain. Upon admission, the patient collapsed and died. The diagnosis of KD was

established during autopsy. The macroscopical and histopathological examination of the heart showed increased

dimensions and weight and multiple thrombi in the coronary arteries with intramural dense polymorphonuclear

inflammatory infiltration and necrosis. Histological examination of the kidneys revealed normal glomerulus, mild

expansion of mesangial matrix, interstitial infiltration with lymphocytes, plasmatocytes and eosinophiles, normal

vessels and normal immunofluorescence.

PMID: 18669530 [PubMed - indexed for MEDLINE]

Pediatr Nephrol. 2002 May;17(5):329-31.

Acute renal failure in typical Kawasaki disease.

Bonany PJ, Bilkis MD, Gallo G, Lago N, Dennehy MV, Sosa del Valle JM, Vallejo G, Cánepa C.

Nephrology Service, Ricardo Gutiérrez Hospital for Children, Callao 157 apt. 5-C, 1022 Buenos Aires, Argentina.

bonany@intramed.net.ar

Comment in:

• Pediatr Nephrol. 2003 Feb;18(2):200; author reply 201.

Abstract

Few cases of Kawasaki disease with acute renal failure have been described and only three articles report

histological findings. We present an 8-year-old boy with typical Kawasaki disease and acute renal failure who did

not require dialysis and had a complete recovery. Pathological findings in percutaneous biopsy included

tubulointerstitial nephropathy with mild mesangial expansion, without vessel involvement or deposits in basal

membrane. These findings were similar to those previously reported. We also detected apoptotic bodies in

tubules.

PMID: 12042888 [PubMed - indexed for MEDLINE]

Pediatr Int. 2008 Apr;50(2):260-1.

Kawasaki disease presenting with macroscopic hematuria.

Motoyama O, Tarui H, Ishihara C, Komatsu H, Matsuyama G, Sawada K, Tateno A, Iitaka K.

Department of Pediatrics, Toho University Medical Center, Sakura Hospital, Chiba, Japan.

motoyan@basil.ocn.ne.jp

PMID: 18353075 [PubMed - indexed for MEDLINE]

Clin Nephrol. 1988 Jan;29(1):47-51.

Renal histology of mucocutaneous lymph node syndrome (Kawasaki

disease).

Salcedo JR, Greenberg L, Kapur S.

UMDNJ New Jersey Medical School, Newark 07103-2757.

Abstract

Renal involvement is well described in patients with mucocutaneous lymph node syndrome (MCLNS), or

Kawasaki disease and is manifested by mild azotemia, hematuria, pyuria or cylinduria, and more often,

proteinuria. Renal morphology during the acute stages of the illness has never been reported. In this paper we

describe the renal histopathologic changes in a child with MCLNS. The glomerular histopathologic findings

suggest immune complex damage to the kidney as a possible mechanism of nephrotoxicity in MCLNS. Presence

of kidney lesions, which speak in favor of the injurious role of immune complexes in MLCNS may be relevant to

the understanding of the pathogenesis of the vascular lesions that are characteristic of this disease.

PMID: 3289806 [PubMed - indexed for MEDLINE]

Nippon Rinsho. 2008 Feb;66(2):315-20.

[Biochemical and immunological laboratory findings in Kawasaki disease]

[Article in Japanese]

Ogawa S.

Department of Pediatrics, Nippon Medical School.

Abstract

There is no specific diagnostic test for Kawasaki disease, but certain laboratory findings are characteristics. In

acute phase of Kawasaki disease, neutrophils with toxic granules, CRP, ESR are elevated. The platelet count is

generally normal in the 1st week of illness and rapidly increases by the 2nd-3rd week of illness. The hepatic

transaminases, total cholesterol, LDL, and total bilirubin are increased in the acute stage. On the other hand, total

protein, albumin and sodium are generally decreased during 1st-2nd week of illness. Sterile pyuria and

cerebrospinal fluid pleocytosis may be present. Moreover, the cytokines, the growth factors, and the adhesion

molecules are elevated according to the intensity of vasculitis.

PMID: 18260330 [PubMed - indexed for MEDLINE]

Clin Pediatr (Phila). 2006 Jun;45(5):446-52.

Extreme thrombocytosis predicts Kawasaki disease in infants.

Nigrovic LE, Nigrovic PA, Harper MB, Chiang VW.

Division of Emergency Medicine, Children's Hospital Boston, Boston, MA 02115, USA.

Abstract

Infants with Kawasaki disease are at high risk of developing life-threatening coronary complications, yet may

elude timely diagnosis because they often lack the full complement of classic clinical features. We retrospectively

studied 26,540 children 1 year of age or less who were evaluated at a tertiary care pediatric emergency

department in whom a platelet count was performed. Among those infants with fever without a source identified,

8.5% with platelet counts of 800,000 cells/mm(3) or greater had Kawasaki disease compared to 0.4% with platelet

counts of less than 800,000 cells/mm(3) (likelihood ratio for Kawasaki disease was 17 [95% confidence interval,

8-34]). Because many infants present atypically, Kawasaki disease should be considered in all children of 1 year

or less with prolonged fever, extreme elevation of the platelet count, and no compelling alternative diagnosis.

PMID: 16891278 [PubMed - indexed for MEDLINE]

Zhonghua Yi Xue Za Zhi (Taipei). 2001 Mar;64(3):168-73.

Clinical spectrum of Kawasaki disease in infants.

Tseng CF, Fu YC, Fu LS, Betau H, Chi CS.

Department of Pediatrics, Taichung Veterans General Hospital, 160, Sec. 3, Taichung-Kang Road, Taichung 407,

Taiwan.

Abstract

BACKGROUND: Kawasaki disease is a common acquired heart disease in children. Only a few reports have

been published concerning Kawasaki disease in infants. This study was performed to assess the clinical spectrum

of Kawasaki disease in infants.

METHODS: Between January 1989 and December 1998, a total of 48 consecutive Kawasaki patients less than

one year of age were enrolled and studied retrospectively. Coronary artery dilation was defined as the internal

diameter of a coronary artery larger than 3 mm. All cases received 2 gm/Kg of intravenous immunoglobulin. We

divided the patients into two groups; group I; coronary artery dilation (+) and group II; coronary artery dilation (-),

and compared the clinical and laboratory data.

RESULTS: Of 273 patients with Kawasaki disease, 48 (17.5%) were less than one year of age. Among these

patients (< 1 year old), the median age was 7.8 +/- 2.8 months (range 2 months to 12 months), and the male to

female ratio was 1.52:1. The incidence of atypical Kawasaki disease was 31.2% (compared with an incidence of

atypical Kawasaki disease among patient more than one year of age of 7.5%; p < 0.001), and that of coronary

artery dilation was 35.4%. Clinical manifestations included fever 100%, extremity change 91.6%, skin rash 89.6%,

conjunctivitis 89.6%, oral mucosa change 89.6%, and cervical lymphadenopathy 0%. Laboratory data revealed

white blood cell count: 15,403 +/- 6,282/mm3, hemoglobin: 10.1 +/- 1.0 gm/dl, neutrophil: 59.2 +/- 13.7%,

lymphocytes: 30.6 +/- 13.1%, platelet count: 456,3000 +/- 216,4000/mm3, and C-reactive protein 8.2 +/- 5.6

mg/dl. Patients with coronary artery dilation had a longer duration of diagnosis, higher incidence of atypical

presentation, lower incidence of conjunctivitis, lower incidence of skin rash, lower incidence of extremity change,

and lower C-reactive protein. The predictive value of coronary artery dilation based on the combination of atypical

presentation, duration of diagnosis, and C-reactive protein was 81.2%.

CONCLUSIONS: Kawasaki disease in infants is associated with a high incidence of atypical presentation and

increased risk of coronary artery dilation. We suggest that in an infant with insufficient diagnostic criteria for

Kawasaki disease, care should be taken to avoid missing atypical Kawasaki disease. Echocardiography is an

important tool for diagnosis of atypical Kawasaki disease.

PMID: 11458622 [PubMed - indexed for MEDLINE]

Zhonghua Er Ke Za Zhi. 2006 Dec;44(12):891-5.

[Therapeutic effectiveness of intravenous immunoglobulin at 1 g/kg and 2

g/kg on Kawasaki disease: a comparative and follow-up study]

[Article in Chinese]

Qin LJ, Wang HW, Hu XF, Liu QJ, Shi H, Wei YX, Chen QJ, Cheng PX.

Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and

Technology, Wuhan 430030, China. qlj54321@yahoo.com.cn

Abstract

OBJECTIVE: To evaluate the effectiveness of intravenous immunoglobulin IVIG, 1 g/kg single intravenous

injection in treating and preventing cardiac consequences of Kawasaki disease (KD) in children.
METHODS: A total of 242 children with KD disease were enrolled in the study. In the randomized controlled trial,

they were randomly divided into two groups: IVIG 1 g/kg group and IVIG 2 g/kg group, with aspirin administered

within the first 7 to 10 days of illness. The occurrence and restoration of coronary artery lesion (CAL) in these two

groups as well as the clinical and laboratory indexes including total fever duration, restoration of cervical

lymphadenopathy, white blood cells count, platelet count, serum immunoglobulin, C reactive protein, erythrocyte

sedimentation rate and EKG were observed. The clinical effectiveness of the groups before and after the

treatment was analyzed.

RESULTS: The age of the 242 children with KD disease ranged from 3 months to 14 years (mean 4.0 +/- 2.8

years old). Male to female ratio was 1.66:1, 83.1% of KD patients were blow 5 years old, 93.4% patients were

followed up with echocardiography at the end of the first year and the follow-up period was (38 +/- 18) months,

ranging from 4 months to 5.4 years; 86.9% of the cases in 1 g/kg group and 91.7% of the cases in 2 g/kg group

had their fever controlled within 48 hours. The difference was not significant (P > 0.05). Serum immunoglobulin

level was markedly enhanced after IVIG. Serum immunoglobulin levels in the patients of 2 g/kg group and 1 g/kg

group were (26.9 +/- 7.4) g/L and (18.3 +/- 6.9) g/L, respectively (P < 0.01). The average duration of fever in IVIG

1 g/kg group was 10.6 days. After the treatment with 1 g/kg of IVIG, the abnormal white blood cells count, platelet

count, C reactive protein, erythrocyte sedimentation rate and abnormal EKG findings were greatly improved (P <

0.001). However, there was no significant difference in the above-mentioned improvement between IVIG 1 g/kg

group and IVIG 2 g/kg group (P > 0.05). In IVIG 1 g/kg group the occurrence of CAL was 29.5%. After the one-

year follow-up, 87.5% CAL restored, but 12.5% did not, among which 9.4% were those of IVIG non-responders. In

IVIG 2 g/kg group the incidence of CAL was 24.2%. After the one-year follow-up, 89.3% CAL restored, but 10.7%

did not, all of which were those of IVIG non-responders. There was no significant difference in the incidence of

CAL between the two groups (P > 0.05).

CONCLUSION: Single intravenous injection of IVIG at 1 g/kg could effectively alleviate the clinical symptoms,

decrease the incidence of CAL and reduce the complication of cardiovascular system. In the treatment of KD, the

therapeutic effectiveness of IVIG at 1 g/kg was not significantly different from that of single intravenous injection of

IVIG at 2 g/kg.

Expert Rev Anti Infect Ther. 2010 Feb;8(2):197-203.

Pathogenesis and management of Kawasaki disease.

Rowley AH, Shulman ST.

Northwestern University Feinberg School of Medicine, Pediatrics, Morton 4-685B, 310 E Superior St, Chicago, IL

60611, USA. a-rowley@northwestern.edu

Abstract

Kawasaki disease (KD) is an acute systemic inflammatory illness of young children that can result in coronary

artery aneurysms, myocardial infarction and sudden death in previously healthy children. Clinical and

epidemiologic features support an infectious cause, but the etiology remains unknown four decades after KD was

first identified by Tomisaku Kawasaki. Finding the cause of KD is a pediatric research priority. We review the

unique immunopathology of KD and describe the current treatment. New research has led to identification of viral-

like cytoplasmic inclusion bodies in acute KD tissues; this finding could lead to identification of the elusive

etiologic agent and result in significant advances in KD diagnosis and treatment. Current management of acute

KD is based upon prospective, multicenter treatment trials of intravenous immunoglobulin (IVIG) with high-dose

aspirin. Optimal therapy is 2 g/kg IVIG with high-dose aspirin as soon as possible after diagnosis during the acute

febrile phase of illness, followed by low-dose aspirin until follow-up echocardiograms indicate a lack of coronary

abnormalities. The addition of one dose of intravenous pulse steroid has not been shown to be beneficial. For the

10-15% of patients with refractory KD, few controlled data are available. Options include repeat IVIG (our

preference), a 3-day course of intravenous pulse methylprednisolone, or infliximab (Remicade). Patients with

mild-to-moderate coronary abnormalities should receive an antiplatelet agent such as low-dose aspirin (3-5

mg/kg/day) or clopidogrel (1 mg/kg/day up to 75 mg), and those with giant (approximately 8 mm diameter) or

multiple coronary aneurysms should receive an antiplatelet agent with an anticoagulant such as warfarin or low-

molecular-weight heparin. Acute coronary obstruction requires acute thrombolytic therapy with a surgical or

percutaneous interventional procedure.

PMID: 20109049 [PubMed - indexed for MEDLINE]PMCID: PMC2845298 [Available on 2010/12/1]