Characteristics of pediatric rhabdomyolysis and the associated risk factors for acute kidney injury: a retrospective multicenter study in Korea

Background@#The clinical features of pediatric rhabdomyolysis differ from those of the adults with rhabdomyolysis; however, multicenter studies are lacking. This study aimed to investigate the characteristics of pediatric rhabdomyolysis and reveal the risk factors for acute kidney injury (AKI) in such cases. @*Methods@#This retrospective study analyzed the medical records of children and adolescents diagnosed with rhabdomyolysis at 23 hospitals in South Korea between January 2007 and December 2016. @*Results@#Among 880 patients, those aged 3 to 5 years old composed the largest subgroup (19.4%), and all age subgroups were predominantly male. The incidence of AKI was 11.3%. Neurological disorders (53%) and infection (44%) were the most common underlying disorder and cause of rhabdomyolysis, respectively. The median age at diagnosis in the AKI subgroup was older than that in the non-AKI subgroup (12.2 years vs. 8.0 years). There were no significant differences in body mass index, myalgia, dark-colored urine, or the number of causal factors between the two AKI-status subgroups. The multivariate logistic regression model indicated that the following factors were independently associated with AKI: multiorgan failure, presence of an underlying disorder, strong positive urine occult blood, increased aspartate aminotransferase and uric acid levels, and reduced calcium levels. @*Conclusions@#Our study revealed characteristic clinical and laboratory features of rhabdomyolysis in a Korean pediatric population and highlighted the risk factors for AKI in these cases. Our findings will contribute to a greater understanding of pediatric rhabdomyolysis and may enable early intervention against rhabdomyolysis-induced AKI.

Clinical Features and Prognosis of Henoch-Schönlein Purpura in Children and Adults: A 13-Year Retrospective Study at a Single Centre

PURPOSE: To investigate differences in clinical features, blood/urinary findings, and prognosis in different age groups of patients with Henoch-Schönlein purpura (HSP). METHODS: A total of 469 patients with HSP were analyzed retrospectively from June 2003 to February 2016. We classified patients into child or adult groups based on their age. RESULTS: The adult group had more patients with anemia (child vs. adult; 7.5% vs. 16.4%), and higher immunoglobulin A (IgA) (30.0% vs. 50.0%) levels, C-reactive protein (34.2% vs. 54.0%) and uric acid (3.1% vs. 12.1%) levels than the child group. The child group was highly positive for Mycoplasma pneumoniae immunoglobulin M (IgM) (34.4%). More patients in the child group presented with high levels of antistreptolysin O (24.7% vs. 2.9%) and high C4 (11.5% vs. 4.2%). Low C3 (1.1% vs. 10.2%) levels, and renal involvement with gross hematuria (8.6% vs. 21.5%), nonnephrotic proteinuria (1.1% vs. 11.2%), and nephrotic syndrome (1.1% vs. 6.0%) were common in the adult group. Adults also had poorer renal outcomes [persistent hematuria/proteinuria (10.5% vs. 32.8%), and chronic kidney disease (0% vs. 11.2%)] than the child group. Risk factors for renal involvement such as older age and higher level of uric acid were only found in the child group. The risk factors for poor renal outcome were nephrotic syndrome in the child group and gross hematuria in the adult group. CONCLUSION: In this study, child and adult groups presented with different clinical manifestations of HSP. We found that risk factors for renal involvement included age and high uric acid level in the child group. Moreover, nephrotic syndrome in the child group and gross hematuria in the adult group increased the risk of poor renal outcome.

Clinical Features and Prognosis of Henoch-Schönlein Purpura in Children and Adults: A 13-Year Retrospective Study at a Single Centre

PURPOSE: To investigate differences in clinical features, blood/urinary findings, and prognosis in different age groups of patients with Henoch-Schönlein purpura (HSP). METHODS: A total of 469 patients with HSP were analyzed retrospectively from June 2003 to February 2016. We classified patients into child or adult groups based on their age. RESULTS: The adult group had more patients with anemia (child vs. adult; 7.5% vs. 16.4%), and higher immunoglobulin A (IgA) (30.0% vs. 50.0%) levels, C-reactive protein (34.2% vs. 54.0%) and uric acid (3.1% vs. 12.1%) levels than the child group. The child group was highly positive for Mycoplasma pneumoniae immunoglobulin M (IgM) (34.4%). More patients in the child group presented with high levels of antistreptolysin O (24.7% vs. 2.9%) and high C4 (11.5% vs. 4.2%). Low C3 (1.1% vs. 10.2%) levels, and renal involvement with gross hematuria (8.6% vs. 21.5%), nonnephrotic proteinuria (1.1% vs. 11.2%), and nephrotic syndrome (1.1% vs. 6.0%) were common in the adult group. Adults also had poorer renal outcomes [persistent hematuria/proteinuria (10.5% vs. 32.8%), and chronic kidney disease (0% vs. 11.2%)] than the child group. Risk factors for renal involvement such as older age and higher level of uric acid were only found in the child group. The risk factors for poor renal outcome were nephrotic syndrome in the child group and gross hematuria in the adult group. CONCLUSION: In this study, child and adult groups presented with different clinical manifestations of HSP. We found that risk factors for renal involvement included age and high uric acid level in the child group. Moreover, nephrotic syndrome in the child group and gross hematuria in the adult group increased the risk of poor renal outcome.

Nonobstructive Bilateral Hydronephrosis & Hydroureter from Nephrogenic Diabetes Insipidus with a Novel Mutation of AQP2 Gene (p.A123G)

Nephrogenic diabetes insipidus (NDI) can cause nonobstructive hydronephrosis. Congenital NDI (CNDI) is caused by a genetic mutation. This case report presents a 12-year-old girl who was incidentally diagnosed with nonobstructive hydronephrosis due to NDI caused by AQP2 gene mutation after being evaluated for microscopic hematuria found on routine health examination at school. The patient's medical and family history was unremarkable, and she complained of nocturia only at the time of the clinic visit. Bilateral hydronephrosis on abdominal ultrasonography prompted a water deprivation test, leading to diagnosis of NDI. Genetic study confirmed p.Asn (AAC)123Ser (AGC) in exon 2 of the AQP2 gene. Polyuria and hydronephrosis improved following arginine-vasopressin therapy. CNDI responsive to treatment should be considered as a possible cause of nonobstructive hydroureter.

Left Paraduodenal Hernia in a 3-year-child

Internal hernia is an uncommon cause of intestinal obstruction, accounting for 1%. The most common cause of internal hernia is left paraduodenal hernia (PDH), which causes acute or recurrent abdominal pain. Due to its nonspecific symptoms, diagnosis of PDH by physical examination is difficult. PDH in children is rarely reported. A 3-year-old-child presented with acute abdominal pain associated with multiple episodes of vomiting. He came to the emergency room three times with abdominal pain. Left PDH was identified by computed tomography. He was taken to the operating room. However cardiac arrest occurred during anesthesia, and he expired. Due to the rarity of PDH in children, it is difficult to consider it as a cause of recurrent abdominal pain. Therefore, considering the possibility of PDH in children with acute or recurrent abdominal pain is recommended.

Interleukin-21 Receptor Gene Polymorphisms in Kawasaki Disease

BACKGROUND AND OBJECTIVES: Interleukin-21 receptor (IL-21R) gene polymorphism is related with the development of systemic vasculitis. In this study, we investigated the polymorphisms of IL-21R gene in patients with Kawasaki disease (KD). SUBJECTS AND METHODS: We genotyped the promoter region of IL-21R gene (-2500 bp to +1 bp) in 100 patients with KD and 100 healthy controls. All study subjects were Korean. We designed five pairs of primers and performed polymerase chain reaction (PCR) and direct sequencing. We analyzed whole promoter sequences of 200 individuals with comparison to reference sequences of IL-21R gene (NG_012222.1/NC_000016.9). RESULTS: We found five single nucleotide polymorphisms (SNPs) of which minor allele frequency (MAF) >0.01 in the promoter region of IL-21R gene. Those are -1681 G>T (chromosome site 27411802), -379 G>A (27413104), -332 G>C (27413151, rs2214537), -237 A>T (27413246), and -53 G>A (27413430). There is no significant difference in MAF of each SNP between patients with KD and healthy controls except -237 A>T. Twenty five patients with KD had more than 1 SNP in contrast to only seven healthy controls had. The patients with KD have significantly more IL-21R gene polymorphisms than controls (odds ratio: 3.0, 95% confidence interval: 1.6-5.6, p=0.0005). There was no significant correlation between IL-21R gene polymorphisms and the serum level of IL-21. The serum level of total IgE was not significantly correlated with the presence of IL-21R gene polymorphisms. CONCLUSION: Our data suggest that the genetic susceptibility profile for KD may include IL-21R gene.

Hereditary Hemorrhagic Telangiectasia with Pulmonary and Splenic Arteriovenous Malformation / 소아알레르기및호흡기학회지

Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is a rare autosomal dominant vascular disorder involving arteriovenous malformation (AVM) due to angiodysplasia. HHT is characterized by mucocutaneous hemorrhagic telangiectasia and AVM of various different organs. The mutated genes in HHT encode proteins that mediate signaling by the transforming growth factor-beta superfamily, leading to migration and proliferation of endothelial cells to finally result in AVMs of various organs. Amongst various affected organs, pulmonary AVM is the most common. This 11-year-old female patient with a past and familial history of frequent epistaxis visited the hospital for abdominal pain and vomiting which developed on the same day. Nodular opacity was found in chest X-ray. Subsequently, AVMs in the lungs and the spleen were recognized in chest computed tomography along with detection of ENG gene mutation. Here we report a case of hereditary hemorrhagic telangiectasia diagnosed by incidental chest X-ray findings followed by genetic and radiologic studies.

A Case of Epstein-Barr Virus Associated Hemophagocytic Lymphohistiocytosis after Scrub Typhus Infection / 임상소아혈액종양

A 7-year-old boy with pancytopenia, cervical lymphadenopathy, interstitial pneumonia, and hepatosplenomegaly was diagnosed with Epstein-Barr Virus (EBV)-associated hemophagocytic lymphohistiocytosis. His clinical course was characterized by hepatorenal syndrome and myocarditis. Based on his serological markers for EBV and an immunochromatography test for scrub typhus, this case was inferred as an EBV infection that was reactivated during tsutsugamushi infection. We treated this patient with the HLH-2004 protocol and administered clarithromycin. Normal ferritin level was achieved within 8 weeks after starting chemotherapy and antibiotics.

Elevated Serum Levels of IL-21 in Kawasaki Disease

PURPOSE: The serum level of immunoglobulin (Ig)E has been reported to be elevated in patients with Kawasaki disease (KD). We investigated whether interleukin (IL)-21, rather than IL-4, could be related to elevated serum levels of IgE in KD. METHODS: Sera from 48 patients with KD and 12 controls with high fever were collected to determine the level of IgE using an immunoassay system and the levels of IL-4 and IL-21 were determined using enzyme-linked immunosorbent assay kits. RESULTS: The median IL-21 level of KD patients was significantly elevated, at 499.5 pg/mL (range: <62.5-1,544 pg/mL), whereas that of controls was <62.5 pg/mL (<62.5-825 pg/mL; P<0.001). The median IL-4 level of KD patients was not elevated (4.0 pg/mL; 2.1-7.6 pg/mL). The median level of total IgE in KD patients was 58.0 IU/mL (5-1,109 IU/mL). No statistically significant correlation was found between IL-21 and total IgE levels (Spearman's R=0.2; P=0.19). CONCLUSIONS: Patients with KD have elevated levels of IL-21 in the serum. IL-21 may play a role in the pathogenesis of KD.

A Case of Epstein-Barr Virus Associated Hemophagocytic Lymphohistiocytosis after Scrub Typhus Infection / 임상소아혈액종양

A 7-year-old boy with pancytopenia, cervical lymphadenopathy, interstitial pneumonia, and hepatosplenomegaly was diagnosed with Epstein-Barr Virus (EBV)-associated hemophagocytic lymphohistiocytosis. His clinical course was characterized by hepatorenal syndrome and myocarditis. Based on his serological markers for EBV and an immunochromatography test for scrub typhus, this case was inferred as an EBV infection that was reactivated during tsutsugamushi infection. We treated this patient with the HLH-2004 protocol and administered clarithromycin. Normal ferritin level was achieved within 8 weeks after starting chemotherapy and antibiotics.

Definition and Diagnostic Criteria of Acute Kidney Injury

Acute renal failure means that the word does not contain a mild kidney injury. In addition, the criteria for acute renal failure per researcher are different, and it is difficult in interpreting the results of research on acute renal failure. Therefore, rather than acute renal failure, a new term "acute kidney injury" meaning to include all the levels of injury is introduced. In 2002, to diagnose by means of serum creatinine, glomerular filtration rate and urine output, a detailed classification of acute kidney injury, the RIFLE criteria has been proposed. In 2007, the RIFLE criteria by transforming, AKIN criteria has been proposed. The pediatric RIFLE criteria for children has also been proposed. The author reviews here these criteria by comparing them.

A Tapping the usefulness of Whole Blood Interferon-gamma Assay for Diagnosing Tuberculosis Infection in Children / 결핵및호흡기질환

BACKGROUND: QuantiFERON(R)-TB Gold In Tube (QFT-G IT) has been used for diagnosing latent tuberculosis infection and active tuberculosis (TB) since 2007. However, there has not been enough data on QFT-G IT for universal use in children. In this study, we evaluated the clinical usefulness of the QFT-G IT in pediatric practice. METHODS: We retrospectively reviewed the clinical records of 70 patients younger than 18 years of age who had taken QFT-G IT and had a tuberculin skin test (TST) between July 2007 and July 2009 at Wonju Christian Hospital. The subjects were divided into two groups, asymptomatic TB exposure group and disease group. Four patients who were taking immunosuppressants during the study period were excluded. RESULTS: A total of 66 immunocompetent children were included in this study. Among 27 asymptomatic children who had contact histories of TB, 6 (22.2%) were found to be positive by QFT-G IT. Eleven (40.7%) and 5 (18.5%) children were found to be positive by TST with cutoff values of > or =5 mm and > or =10 mm, respectively. Agreement was fair to good between QFT-G IT and TST (kappa=0.59: cutoff value > or =5 mm, kappa=0.7: cutoff value > or =10 mm). In disease group, 14 patients (35.9%) were diagnosed with active tuberculosis, 8/14 (57.1%) were positive on TST and 9/14 (64.3%) on QFT-G IT. The positive rate of acid-fast bacilli smear, TB-polymerase chain reaction, and culture for tuberculosis was 11% (1/9), 27.3% (3/11) and 33.3% (3/9), respectively. CONCLUSION: Our data support that the QFT-G IT can be used as an additional diagnostic tool for latent and active tuberculosis infection in children.

Relationship Between Gallbladder Distension and Lipid Profiles in Kawasaki Disease

BACKGROUND AND OBJECTIVES: Kawasaki disease (KD) is an acute systemic vasculitis in children which causes coronary arterial dilatation (CAD) and gallbladder distension (GBD). There is a dearth of investigating the relationship between the severity of KD and GBD with lipid profiles. SUBJECTS AND METHODS: A total of 80 patients with 'complete KD' who were diagnosed from January 2005 to May 2009 was enrolled in this study. Serum cholesterol {total, high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C)}, triglyceride (TG), complete blood count, inflammation markers {erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)} were measured at the time of admission during febrile period. Echocardiography and abdominal sonogram were performed in all patients to determine CAD and gallbladder size. According to GBD, patients with KD were classified as patients with GBD and patients without GBD. Between two groups, demographic and clinical data were analyzed. RESULTS: The serum level of LDL-C was significantly lower in patients with GBD (p=0.03) compared with patients without GBD or febrile control. There was no significant difference in inflammatory indices between patients with GBD and patients without GBD. GBD was not significant risk factor of CAD in this study (odds ratio=2.0, 95% confidence interval=0.82-5.3, p=0.16). CONCLUSION: This is the first study that highlights the relationship between the GBD and lipid metabolism in patients with KD. This study provides clinical insights about potential mechanism underpinning the relationship between the GBD and lipid metabolism.

Predicting Factors for Refractory Kawasaki Disease

BACKGROUND AND OBJECTIVES: About 10-15% of Kawasaki disease (KD) is refractory to intravenous immunoglobulin (IVIG) therapy. This study was designed to investigate the predicting factors for refractory KD. SUBJECTS AND METHODS: We reviewed retrospectively the clinical records of 77 patients with typical KD admitted at Wonju Christian Hospital from January, 2005, to December, 2008. The variance of laboratory and demographic parameters between the IVIG-responsive group and IVIG-resistant group were analyzed. Thirteen patients with urinary tract infections were randomly collected as a febrile control group. RESULTS: Among 77 patients diagnosed with complete KD, 13 patients (16.9%) were IVIG-resistant. The febrile period and hospital days were significantly longer in the IVIG-resistant group than IVIG-responsive group (p<0.001, p=0.002). Serum levels of albumin and sodium were significantly lower in the IVIG-resistant group (p=0.025). The Kobayashi score could differentiate these two groups (p=0.015). Fewer lymphocytes was observed during the subacute phase in the IVIG-resistant group (p=0.032). Coronary arterial dilatations (CADs) were observed in 10.9% (7/64) of IVIG-responders and 38.5% (5/13) of IVIG-resistant patients (p=0.038). CONCLUSION: The percentage of neutrophils and lymphocytes in patients with KD, in addition to known risk factors for refractory KD, may help predict IVIG-resistance in patients with KD.

A Case about Cyclosporine Treatment of Kimura's Disease Associated with Steroid Dependant Nephrotic Syndrome

Kimura's disease is a chronic inflammatory disorder of unknown etiology. A 14 year old boy suffering from steroid dependant nephrotic syndrome, was presented with relapsing painless subcutaneous masses on the left buccal area. Blood analysis showed increased IgE and eosinophilia. During 4 years follow up, he was been treated by low dose steroid and short term cyclosporine. Consequently, frequent relapses of subcutaneous masses and nephrotic syndrome has been relieved. Cyclosporine treatment combined with steroid may be useful for preventing frequent relapse of Kimura's disease.

Effects of Ketotifen on an Experimental Model of IgA Nephropathy

PURPOSE: The intestinal mucosal defect has been known as one of the pathogenicmechanisms of IgA nephropathy. Oral antigens usually induce the activation of Th2 cells and mast cells. These cells secrete cytokines IL-4, IL-5 and TGF-beta, which increase IgA production. Although ketotifen (benzocycloheptathiophene) is an H1 antagonist and a mast cell membrane stabilizer, it could protect the gastrointestinal membrane through inhibiting the production of IL-4, IL-5, PGE2, and LTB4, and decreasing the activity of nitric oxide synthease. Therefore, we have investigated if ketotifen may protect the development of IgA nephropathy with an oral antigen. METHODS: ICR mice were used as an animal model orally with Poliovax only [ketotifen (-)], the other group was given oral ketotifen [ketotifen (+)] in addition to Poliovax. RESULTS: Mesangial IgA deposition developed in 11 out of the 18 mice in the ketotifen (-) group, while in three out of the nine mice in ketotifen (+) group. The mesangial change developed in 16 out of the 18 mice in the ketotifen (-) group, while in five out of the nine mice in the ketotifen (+) group. Serum IL-4 and IL-5 levels were not significantly lower in the latter group than in the former. CONCLUSION: According to the statistical results from the above, ketotifen therapy would be beneficial to reducing mesangial changes in IgA nephropathy.

A Case of Bacteremia Caused by Rothia dentocariosa / 대한임상미생물학회지

Rothia dentocariosa, a pleomorphic gram-positive branching bacillus, is a common inhabitant of the nose and throat. It is a well-known causative agent of dental plaques and periodontal diseases. Although generally regarded as having a low virulence to humans, R. dentocariosa has been recognized as causative agents of infective endocarditis and bacteremia with increasing frequency. Consequently, it can be a very serious pathogen when isolated from usually sterile sites such as blood or cerebrospinal fluid. We report a case of Rothia dentocariosa bacteremia without endocarditis in a 17-month-old male patient with fever, vomiting and diarrhea.

Treatment of Cytomegalov irus-associated IgA Nephropathy by Deflazacort and Intrav enous Immunoglobulin

It has been suspected that various infections, including cytomegalovirus(CMV) infection, are associated with IgA nephropathy. In case of CMV infection, ganciclovir is known to be a treatment of choice for severe CMV infection in general. But ganciclovir has a lot of severe toxicity, so children with normal immunity are seldom treated by ganciclovir when CMV infection is suspected. On the other hand, intravenous immunoglobulin can also be used to treat CMV infection.

A Multicenter Prospective Study of the Effect of Imipramine and Desmopressin on Arousability in Children with Nocturnal Enuresis / 대한비뇨기과학회지

PURPOSE: We performed a multicenter, prospective study to evaluate the efficacy of imipramine and desmopressin to improve arousability and prevent nocturnal enuresis(NE). MATERIALS AND METHODS: The total of 48 children with NE were given questionnaires that included a scoring system for the assessing arousal from sleep. They were assigned into two groups: group 1(imipramine 25 mg, 3 girls and 16 boys, mean age 7.9 years), group 2(desmopressin 0.2 mg, 9 girls and 9 boys, mean age 7.5 years). The assessment of arousability was repeated 2 weeks and 4 weeks after medication. Eleven children were excluded because of incomplete data. RESULTS: Mean wetting events in group 1 decreased from 8.8 to 5.1 times(2 weeks) and 3.0 times(4 weeks)(p=0.009) versus 10.2 to 5.5 times(2 weeks) and 6.4 times(4 weeks)(p=0.007) for group 2. The mean threshold of arousability in group 1 was 4.9(baseline), 4.4(2 weeks), and 3.7(4 weeks), and, for group 2, 5.1(baseline), 4.8(2 weeks), and 4.8(4 weeks). The two groups were not different(p=0.14, p=0.73). CONCLUSIONS: Imipramine and desmopressin, which are commonly used in treating NE in Korea, influenced wetting events but not arousability.

Microalbuminuria

Many children with microscopic hematuria have been found on school screening examinations. There are not, however, nation-wide criteria for us(specifically, pediatric nephrologists) how to take care of them. Recently, quite a few research papers concerning microalbuminuria with microscopic hematuria, which can predict the renal pathological findings, are published. Here I have reviewed articles on microalbuminuria which gives us the information how to manage microscopic hematuria.