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.

Acute kidney injury in pediatric patients with rhabdomyolysis / 소아과

PURPOSE: This study aimed to evaluate the clinical findings in pediatric rhabdomyolysis and the predictive factors for acute kidney injury (AKI) in Korean children. METHODS: Medical records of 39 Korean children, who were newly diagnosed with rhabdomyolysis from January 2008 to December 2015, were retrospectively analyzed. The diagnosis was made from the medical history, elevated serum creatinine kinase level >1,000 IU/L, and plasma myoglobin level >150 ng/mL. Patients with muscular dystrophy and myocardial infarction were excluded. RESULTS: The median patient age at diagnosis was 14.0 years (range, 3–18 years), and the male to female ratio was 2.5. The most common presenting symptom was myalgia (n=25, 64.1%), and 14 patients (35.9%) had rhabdomyolysis-induced AKI. Eighteen patients (46.2%) had underlying diseases, such as epilepsy and psychotic disorders. Ten of these patients showed rhabdomyolysis-induced AKI. The common causes of rhabdomyolysis were infection (n=12, 30.7%), exercise (n=9, 23.1%), and trauma (n=8, 20.5%). There was no difference in the distribution of etiology between AKI and non-AKI groups. Five patients in the AKI group showed complete recovery of renal function after stopping renal replacement therapy. The median length of hospitalization was 7.0 days, and no mortality was reported. Compared with the non-AKI group, the AKI group showed higher levels of peak creatinine kinase and myoglobin, without statistical significance. CONCLUSION: The clinical characteristics of pediatric rhabdomyolysis differ from those observed in adult patients. Children with underlying diseases are more vulnerable to rhabdomyolysis-induced AKI. AKI more likely develops in the presence of a high degree of albuminuria.

Pharmacological therapy of nocturnal enuresis

Nocturnal enuresis is a common problem of children during sleeping at preschool or school age. It may affect negatively the psychosocial development of children. Children with enuresis may have lower self-esteem and lower quality of life. There are three main factors of the pathophysiology of enuresis: high nocturnal urine production, nocturnal low bladder capacity or increased detrusor muscle activity, and arousal disorder. As pharmacological therapy for nocturnal enuresis, several medications including desmopressin, anticholinergics, imipramine have been used for a long time. As first-line therapy, desmopressin combined with anticholinergics has good response in primary monosymptomatic nocturnal enuresis. Because imipramine has serious and lethal cardiotoxic effect with overdosage, imipramine should be prescribed after EKG to rule out the conduction problem of heart.

Posterior reversible encephalopathy syndrome caused by presumed Takayasu arteritis / 소아과

Takayasu arteritis (TA) is a chronic inflammatory disease of unknown etiology that affects mainly the aorta, main aortic branches, and pulmonary arteries. Diverse neurological manifestations of TA have rarely been reported in children. Posterior reversible encephalopathy syndrome (PRES) is a neuroradiological condition that presents with headache, seizure, visual disturbances, and characteristic lesions on imaging. Inflammatory condition and severe hypertension in TA can cause PRES. We report of a 5-year-old girl with presumed TA who presented with PRES and chronic total occlusion in the renal artery. The findings on magnetic resonance imaging suggested PRES. Left nephrectomy was performed for total occlusion of the left renal artery, and the confirmatory diagnosis of TA was based on the pathologic findings of the renal artery.

A novel mutation of CLCNKB in a Korean patient of mixed phenotype of Bartter-Gitelman syndrome / 소아과

Bartter syndrome (BS) is an inherited renal tubular disorder characterized by low or normal blood pressure, hypokalemic metabolic alkalosis, and hyperreninemic hyperaldosteronism. Type III BS is caused by loss-of-function mutations in CLCNKB encoding basolateral ClC-Kb. The clinical phenotype of patients with CLCNKB mutations has been known to be highly variable, and cases that are difficult to categorize as type III BS or other hereditary tubulopathies, such as Gitelman syndrome, have been rarely reported. We report a case of a 10-year-old Korean boy with atypical clinical findings caused by a novel CLCNKB mutation. The boy showed intermittent muscle cramps with laboratory findings of hypokalemia, severe hypomagnesemia, and nephrocalcinosis. These findings were not fully compatible with those observed in cases of BS or Gitelman syndrome. The CLCNKB mutation analysis revealed a heterozygous c.139G>A transition in exon 13 [p.Gly(GGG)465Glu(GAG)]. This change is not a known mutation; however, the clinical findings and in silico prediction results indicated that it is the underlying cause of his presentation.

Plasmaphresis therapy for pulmonary hemorrhage in a pediatric patient with IgA nephropathy / 소아과

IgA nephropathy usually presents as asymptomatic microscopic hematuria or proteinuria or episodic gross hematuria after upper respiratory infection. It is an uncommon cause of end-stage renal failure in childhood. Pulmonary hemorrhage associated with IgA nephropathy is an unusual life-threatening manifestation in pediatric patients and is usually treated with aggressive immunosuppression. Pulmonary hemorrhage and renal failure usually occur concurrently, and the pulmonary manifestation is believed to be caused by the same immune process. We present the case of a 14-year-old patient with IgA nephropathy who had already progressed to end-stage renal failure in spite of immunosuppression and presented with pulmonary hemorrhage during oral prednisone treatment. His lung disease was comparable to diffuse alveolar hemorrhage and was successfully treated with plasmapheresis followed by oral prednisone. This case suggests that pulmonary hemorrhage may develop independently of renal manifestation, and that plasmapheresis should be considered as adjunctive therapy to immunosuppressive medication for treating IgA nephropathy with pulmonary hemorrhage.

Burkholderia Cepacia Causing Nosocomial Urinary Tract Infection in Children

PURPOSE: Burkholderia cepacia is an aerobic, glucose-non-fermenting, gramnegative bacillus that mainly affects immunocompromised and hospitalized patients. Burkholderia cepacia has high levels of resistance to many antimicrobial agents, and therapeutic options are limited. The authors sought to analyze the incidence, clinical manifestation, risk factors, antimicrobial sensitivity and outcomes of B. cepacia urinary tract infection (UTI) in pediatric patients. METHODS: Pediatric patients with urine culture-proven B. cepacia UTI between January 2000 and December 2014 at Samsung Medical Center, a tertiary referral hospital in Seoul, Republic of Korea, were included in a retrospective analysis of medical records. RESULTS: Over 14 years, 14 patients (male-to-female ratio of 1:1) were diagnosed with B. cepacia UTI. Of 14 patients with UTI, 11 patients were admitted to the intensive care unit, and a bladder catheter was present in 9 patients when urine culture was positive for B. cepacia. Patients had multiple predisposing factors for UTI, including double-J catheter insertion (14.2%), vesico-ureteral reflux (28. 6%), congenital heart disease (28.6%), or malignancy (21.4%). Burkholderia cepacia isolates were sensitive to piperacillin-tazobactam and sulfamethoxazole-trimethoprim, and resistant to amikacin and colistin. Treatment with parenteral or oral antimicrobial agents including piperacillin-tazobactam, ceftazidime, meropenem, and sulfamethoxazole-trimethoprim resulted in complete recovery from UTI. CONCLUSION: Burkholderia cepacia may be a causative pathogen for nosocomial UTI in pediatric patients with predisposing factors, and appropriate selection of antimicrobial therapy is necessary because of high levels of resistance to empirical therapy, including aminoglycosides.

The Antibiotic Resistance Pattern of Gram-Negative Bacteria in Children Younger Than 24 Months with a Urinary Tract Infection: A Retrospective Single-Center Study over 15 Consecutive Years

PURPOSE: We investigated trends in antibiotic resistance for gram-negative bacteria in infants with a urinary tract infection (UTI) over 15 years at a single institution. METHODS: A retrospective chart review was conducted for children younger than 24 months who visited the emergency room and were diagnosed with a UTI between January 2000 and December 2014. We selected urine culture data that grew Escherichia coli and Klebsiella pneumoniae. Baseline clinical information and results of antimicrobial susceptibility tests were analyzed by dividing the 15-year study time frame into three periods (A: 2000-2004, B: 2005-2009, and C: 2010-2014). RESULTS: During the study period, 478 applicable children were identified (E. coli, 89.7% and K. pneumoniae, 10.3%). Antibiotic resistance to third-generation cephalosporins was increased from period A to period C (A, 2.1%; B, 8.3%; C, 8.8%; P=0.025). Resistance to quinolones also showed a steady pattern during periods A to C, although it was not statistically significant (A, 7.9%; B, 9.7%; C, 12.4%; P=0.221). The incidence of Extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacteria increased from period A to period C (A, 1.4%; B, 7.6%; C, 8.2%; P=0.012). CONCLUSION: This study revealed that the common uropathogens E. coli and K. pneumoniae experienced increasing resistance rates against third-generation cephalosporins and a constant antibiotic resistance to quinolones in children younger than 24 months. We also showed a recent increased incidence of ESBL-producing gram-negative bacteria in patients with community-acquired UTIs. Therefore, it is necessary to actively surveil resistance in order to properly select empirical antibiotics.

The Use of Nafamostat Mesilate as an Anticoagulant during Continuous Renal Replacement Therapy for Children with a High Risk of Bleeding

PURPOSE: Nafamostat mesilate (NM), a synthetic serine protease inhibitor, has been investigated as an anticoagulant for adult patients with a high risk of bleeding, who need chronic renal replacement therapy (CRRT). However, little is known about the use of NM as an anticoagulant in pediatric CRRT. The aim of this study was to evaluate the ideal dosage, efficacy, and safety of NM in pediatric CRRT. METHODS: We conducted a retrospective study of 40 pediatric patients who had undergone at least 24 h of venovenous CRRTs between January 2011 and October 2013. We divided the patients according to risk of bleeding. Those at high risk received no anticoagulation (group 1) or NM as an anticoagulant (group 2), while those at low risk received heparin (group 3). RESULTS: Forty patients (25 male and 15 female; mean age, 8.2+/-6.6 years) were enrolled. The mean duration of CRRT was 13.0 days, and the survival rate was 57.5%. The mean hemofilter lifespan was 39.3 h in group 1 and 11.3 h in group 3. In group 2, hemofilter lifespan was extended from 7.5 h to 27.4 h after the use of NM (P=0.001). The mean hemofilter lifespan with NM was greater than with heparin (P=0.018). No patient experienced a major bleeding event during treatment with NM. CONCLUSION: NM may be a good alternative anticoagulant in pediatric patients with a high risk of bleeding requiring CRRT, and is not associated with bleeding complications.

Kikuchi-Fujimoto Disease, A Possible Complication of Rituximab Treatment

Rituximab, a chimeric anti-CD20 IgG1 monoclonal antibody, has been used as a rescue therapy for steroid-dependent or refractory nephrotic syndrome. However, the adverse effects of rituximab are yet to be investigated. We report a case of a 9-year-old boy with steroid-dependent nephrotic syndrome who developed Kikuchi-Fujimoto disease after several cycles of rituximab therapy. Kikuchi-Fujimoto disease is a benign, self-limited necrotizing histiocytic lymphadenitis of unknown etiology. In the present case, Kikuchi-Fujimoto disease developed when the peripheral blood B-cell count of the patient was at nadir, and the lesion regressed slowly but spontaneously after recovery of the B-cell count. To our knowledge, although the pathologic diagnosis of Kikuchi-Fujimoto disease was unavailable, this is the first report of Kikuchi-Fujimoto disease with clinical diagnosis as a possible adverse effect of rituximab.

Microalbuminuria in Normal Korean Children

PURPOSE: Although microalbuminuria is known as a predictor of clinical nephropathy and cardiomyopathy, few studies have investigated the incidence and reference range of microalbuminuria in healthy children. This study aimed to establish a reference range and to study the age-related trend for spot urine microalbumin/creatinine ratio in a Korean pediatric population. MATERIALS AND METHODS: 352 healthy children were studied from July 2007 through March 2010. Height, weight, serum creatinine, spot urine microalbumin/creatinine ratio, and glomerular filtration rate (GFR) were obtained for each subject. We divided the study population into 5 groups according to age, and compared the spot urine microalbumin/creatinine ratio with other variables using one-way analysis of variance (ANOVA), regression analysis and Pearson's correlation analysis. RESULTS: In this study, the data showed that the spot urine microalbumin/creatinine ratio decreased with age: 1-12 months, 22.72+/-13.80 mg/mmol (2SD: 3.33-54.40 mg/mmol); 13-28 months, 16.34+/-9.58 mg/mmol (2SD: 3.16-35.19 mg/mmol); 29-48 months, 13.12+/-9.74 mg/mmol (2SD: 3.01-41.57 mg/mmol); 4-6 years, 10.58+/-8.13 mg/mmol (2SD: 0.00-30.19 mg/mmol); and 7-19 years, 5.13+/-5.44 mg/mmol (2SD: 0.45-14.45 mg/mmol). The spot urine microalbumin/creatinine ratio showed correlation with age, height, height z-score, weight, weight z-score, GFR, body mass index (BMI) and body surface area (BSA). CONCLUSION: The spot urine microalbumin/creatinine ratio in normal Korean children decreased with age. This ratio could potentially be used to establish reference ranges and cutoff values for Korean children and to predict nephropathy and cardiomyopathy.

The relationships between clinical variables and renal parenchymal disease in pediatric clinically suspected urinary tract infection / 소아과

PURPOSE: To evaluate the significance of clinical signs and laboratory findings as predictors of renal parenchymal lesions and vesicoureteral reflux (VUR) in childhood urinary tract infection (UTI). METHODS: From July 2005 to July 2008, 180 patients admitted with a first febrile UTI at the Pediatric Department of Konkuk University Hospital were included in this study. The following were the clinical variables: leukocytosis, elevated C-reactive protein (CRP), positive urine nitrite, positive urine culture, and fever duration both before and after treatment. We evaluated the relationships between clinical variables and dimercaptosuccinic acid (DMSA) scan and voiding cystourethrography (VCUG) results. RESULTS: VCUG was performed in 148 patients; of them, 37 (25.0%) had VUR: 18 (12.2%) had low-grade (I-II) VUR, and 19 (10.5%) had high-grade (III-V) VUR. Of the 95 patients who underwent DMSA scanning, 29 (30.5%) had cortical defects, of which 21 (63.6%) had VUR: 10 (30.3%), low-grade (I-II) VUR; and 11 (33.3%), high-grade VUR. Of the 57 patients who were normal on DMSA scan, 8 (14.0%) had low-grade VUR and 6 (10.5%) had high-grade VUR. The sensitivity, specificity, and positive and negative predictive values of the DMSA scan in predicting high-grade VUR were 64.7%, 69.9%, 33.3%, and 89.5%, respectively. Leukocytosis, elevated CRP, and prolonged fever (> or =36 hours) after treatment were significantly correlated with the cortical defects on DMSA scans and high-grade VUR. CONCLUSION: Clinical signs, including prolonged fever after treatment, elevated CRP, and leukocytosis, are positive predictors of acute pyelonephritis and high-grade VUR.

Adverse Events Following Yellow Fever Vaccination in Korean Children / 소아감염

PURPOSE:Yellow fever, a mosquito-borne viral hemorrhagic fever, is one of the most lethal diseases. Recently there have been an increasing number of Korean children who have travelled to yellow fever endemic zones and were administered yellow fever vaccine (YFV). Therefore, we carried out this study to provide child travelers with safety information of YFV. METHODS:This study was conducted at the International Clinic of National Medical Center in Seoul between April 2007 and June 2008 for the evaluation of adverse events of YFV. One hundred twenty- five children received YFV (17-DD) and were prospectively monitored for adverse events through telephone interviews on day 3, 6, 9, 16, 23 and 30 after vaccination. RESULTS:Adverse events were observed in 31 (24.8%) of 125 child travelers who received the YFV. The mean age was 12.5+/-5.0 years. Sixty-six of the child travelers (52.8%) were males. The common adverse events were pain in 11 (8.8%), swelling in 8 (6.4%) and redness in 7 children (5.6%) at the injection site. The systemic adverse events included mild fever in 5 (4.0%), headache in 5 (4.0%), cough in 4 (3.2%), abdominal pain in 3 (2.4 %), and vomiting in 2 children (1.6%). Most of the adverse events were detected within 7 days of administration and there were no differences in adverse events by gender or age. All travelers who had complained of symptoms improved spontaneously or following symptomatic treatment. CONCLUSION:This study showed that YFV is well-tolerated and there were no reports of severe adverse events. Studies are ongoing to clarify the cause and risk factors for rare adverse events.

Analysis of the factors influencing headache and backache following lumbar puncture / 소아과

PURPOSE: This study aimed to examine the factors influencing the appearance of headache and backache following diagnostic lumbar puncture in children, focusing on the need for strict bed rest after lumbar puncture. METHODS: We studied 70 two-fifteen-year-old pediatric patients who underwent diagnostic lumbar puncture from July 2005 to July 2007 at Konkuk University Hospital. We divided them into two groups. Patients in the first group (n=24) were allowed free mobility and patients in the second group (n=46) were to have strict bed rest for four hours after puncture. Data were analyzed by age, sex, number of puncture attempts, cell counts and pressure in the cerebrospinal fluid (CSF), duration of bed rest, and occurrence of headache and backache. RESULTS: The rate of complications was not significantly related to sex, age, presence of enterovirus, CSF pressure, or postural headache. The occurrence of headache was significantly correlated with white blood cell (WBC) count in CSF (P=0.043). Symptom frequency did not differ significantly between the groups. Backache was significantly related to the frequency of puncture attempts (P=0.046). CONCLUSION: Strict bed rest following diagnostic lumbar puncture in children does not influence headaches and backaches. These are respectively related to the WBC count on the CSF profile and the frequency of attempts. Therefore, after lumbar puncture, absolute bed rest is not necessary and patients are more comfortable with free mobility.

Disorder of Sex Development with 5alpha-reductase Deficiency in Identical Twins / 대한소아내분비학회지

Children with abnormal sex development may present with ambiguous genitalia in the newborn period or lacking of secondary sexual characteristics in puberty. Clinicians should make a prompt and accurate diagnosis and counsel parents on therapeutic options to minimize or avoid medical and psychological complications. 5alpha-reductase deficiency is a rare autosomal recessive disorder of sex development caused by a mutation of the 5alpha-reductase type 2 gene. As a result, there is an abnormality in conversion of testosterone (T) to dihydrotestosterone (DHT) and children with 5alpha-reductase deficiency are born with ambiguous genitalia. Here, we report identical twins who presented with ambiguous genitalia with a 46,XY karyotype and were diagnosed as 5alpha-reductase deficiency.

A Case of Neonatal Jaundice due to Anti-Jk(b) / 대한주산의학회잡지

The Kidd (Jk) system is one of the most important blood group systems in transfusion medicine due to immediate or delayed hemolytic transfusion reactions as well as hemolytic disease of newborn (HDN). We experienced a case of jaundice and hemolytic anemia in a newborn due to anti-Jk(b) incompatibility appearing within the first 24 hours of life. The infant's direct and indirect antiglobulin tests were positive. There were no ABO and Rh (D) incompatibilities between the mother and the baby. Direct Coomb's IgG was strongly positive but C3d was negative. We started the exchange transfusion with the whole blood and had a favorable outcome. We report this case with a brief review of relevant literature.

A Case of Peters' Anomaly / 대한주산의학회잡지

Peters' anomaly is a rare form of anterior segment dysgenesis in which abnormal cleavage of the anterior chamber occurs. It is defined as a congenital central corneal opacity with corresponding defects in the posterior corneal stroma, Descemet's membrane, and endothelium. Peters' anomaly may be associated with other ocular or systemic abnormalities like microphthalmos, colobomata, retinal and optic nerve dysplasia, developmental delay, central nervous system defects, craniofacial abnormalities, seizure disorders, genitourinary malformations, and cardiopulmonary defects. Peters' anomaly may also have an inherited pattern, mostly autosomal recessive and dominant inheritance. Mutations involve the PAX6 gene, RIEG1 gene, and other genes. Management of infants with congenital corneal opacity is quite difficult, but penetrating keratoplasty is known as the effective treatment for visual outcome if it is performed within the first 3 months of life. We recently experienced a case of Peters' anomaly in association with atrial septal defect & chromosomal abnormality, therefore herein present it with a brief review of relevant literature.

A Case of Peters' Anomaly / 대한주산의학회잡지

Peters' anomaly is a rare form of anterior segment dysgenesis in which abnormal cleavage of the anterior chamber occurs. It is defined as a congenital central corneal opacity with corresponding defects in the posterior corneal stroma, Descemet's membrane, and endothelium. Peters' anomaly may be associated with other ocular or systemic abnormalities like microphthalmos, colobomata, retinal and optic nerve dysplasia, developmental delay, central nervous system defects, craniofacial abnormalities, seizure disorders, genitourinary malformations, and cardiopulmonary defects. Peters' anomaly may also have an inherited pattern, mostly autosomal recessive and dominant inheritance. Mutations involve the PAX6 gene, RIEG1 gene, and other genes. Management of infants with congenital corneal opacity is quite difficult, but penetrating keratoplasty is known as the effective treatment for visual outcome if it is performed within the first 3 months of life. We recently experienced a case of Peters' anomaly in association with atrial septal defect & chromosomal abnormality, therefore herein present it with a brief review of relevant literature.

Comparative study of therapeutic effects according to duration of medium-dose aspirin therapy at the acute stage of Kawasaki disease / 소아과

PURPOSE: This study was performed to compare the therapeutic effects according to duration of medium-dose aspirin(50-60 mg/kg/day) therapy at the acute stage of Kawasaki disease(KD). METHODS: Total 87 patients with KD were enrolled in this study. We performed retrospective analysis of clinical characteristics and echocardiographic findings based on medical records. Patient were randomly divided into 2 groups according to the duration of aspirin therapy at the acute stage of KD. Long-term group(LG, n=55) was administered medium-dose aspirin for 2 weeks after diagnosis of KD, and short-term group(SG, n=32) for 48 hours after intravenous immunoglobulin(IVIG) administration. The parameters of therapeutic effects were duration of fever after IVIG administration, incidence of unresponsive patients to single administration of IVIG, and development of transient dilatation or aneurysm of coronary arteries. RESULTS: There was no significant difference in the duration of fever after IVIG between the both group(LG 1.7+/-1.1 days, SG 1.8+/-1.1 days; P=0.588). The incidences of unresponsive patient to the single administration of IVIG were 5.5 percent, 6.3 percent in the each group. Transient dilatation of coronary arteries occurred at 18.2 percent(10/55) in the LG, and 15.6 percent(5/32) in the SG(P= 0.761). Prevalence of coronary aneurysm after subacute stage were 7.3 percent(4/55) in the LG, and 9.4 percent(3/32) in the SG(P=0.728). CONCLUSION: There was no significant difference in the therapeutic effects between long-term(2 weeks) and short-term(48 hours) administration of medium-dose aspirin at the acute stage of KD.

A Case of Epidermolysis Bullosa Letalis

No abstract available.