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.

Intellectual Functioning of Pediatric Patients with Chronic Kidney Disease:Results from the KNOW-Ped CKD

Background@#Chronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD. @*Methods@#Eighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6–16 years), or Wechsler Adult Intelligence Scale (> 16 years). @*Results@#The mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < −1.88), failure to thrive (weight Z scores < −1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs. @*Conclusion@#On linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time.

Intellectual Functioning of Pediatric Patients with Chronic Kidney Disease:Results from the KNOW-Ped CKD

Background@#Chronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD. @*Methods@#Eighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6–16 years), or Wechsler Adult Intelligence Scale (> 16 years). @*Results@#The mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < −1.88), failure to thrive (weight Z scores < −1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs. @*Conclusion@#On linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time.

A Comprehensive Review of Coronavirus Disease 2019: Epidemiology, Transmission, Risk Factors, and International Responses

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide pandemic. The first reports of patients with COVID-19 were provided to World Health Organization on December 21, 2019 and were presumably associated with seafood markets in Wuhan, China. As of October 25, 2020, more than 42 million cases have been confirmed worldwide, with more than 1.1 million deaths. Asymptomatic transmission contributes significantly to transmission, and clinical features are non-specific to the disease. Thus, the diagnosis of COVID-19 requires specific viral RNA testing. The disease demonstrates extensive human-to-human transmissibility and has infected healthcare workers at high rates. Clinical awareness of the epidemiology and the risk factors for nosocomial transmission of COVID-19 is essential to preventing infection. Moreover, effective control measures should be further identified by comprehensive evaluation of hospital and community responses. In this review, we provide a comprehensive update on the epidemiology, presentation, transmission, risk factors, and public health measures associated with COVID-19. We also review past insights from previous coronavirus epidemics [i.e., severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS)] to suggest measures to reduce transmission.

A Review of Pre-Exposure Prophylaxis Adherenceamong Female Sex Workers

Globally and in Africa specifically, female sex workers (FSWs) are at an extraordinarily high risk of contracting human immunodeficiencyvirus (HIV). Pre-exposure prophylaxis (PrEP) has emerged as an effective and ethical method with which to preventHIV infection among FSWs. PrEP efficacy is, however, closely linked to adherence, and adherence to PrEP among FSWs is a complexand interrelated process that has been shown to be of importance to public health policies and HIV control and interventionprograms. This comprehensive review categorizes barriers to and facilitators of adherence to HIV PrEP for FSWs, and describes fivestrategies for promoting PrEP adherence among FSWs. These strategies encompass 1) a long-term educational effort to decreasethe stigma associated with sex work and PrEP use, 2) education on how PrEP works, 3) lifestyle modification, 4) research on nextgenerationPrEP products to address the inconvenience of taking daily pills, and 5) integration of PrEP into existing services, suchas social services and routine primary care visits, to reduce the economic burden of seeking the medication. Our review is expectedto be useful for the design of future PrEP intervention programs. Multidisciplinary intervention should be considered to promotePrEP adherence among FSWs in order to help control the HIV epidemic.

Expression of Phospholipase A2 Receptor in PediatricHepatitis B Virus-Related Membranous Nephropathy

Purpose@#Hepatitis B virus (HBV) infection is among etiologies of secondarymembranousnephropathy (MN) in pediatric patients. We evaluated expressionof phospholipase A2 receptor (PLA2R), a specific target antigen of primary MN, inpediatric HBV-related MN. @*Methods@#We retrospectively reviewed patients with biopsy-proven HBV-relatedMN from the renal biopsy registry and electronic medical records of SeveranceHospital, Seoul, Korea, from 1993 to 2004. Paraffin-embedded human kidneytissues were retrieved and immunohistochemically stained for PLA2R. @*Results@#Ten pediatric patients with 13 biopsied specimens were reviewed. Thepredominant pathological stage was stage II–III, and second was stage II. Theintensity of staining for IgG was greatest, with less intense staining for IgM, IgA,C3, C4, and C1q. All the patients had angiotensin-converting enzyme inhibitorcombined with glucocorticoid, and four patients converted to cyclosporine treatmentfrom glucocorticoid monotherapy. Urinalysis of all the patients normalizedafter variable period. PLA2R staining was demonstrated in the outer glomerulus in3 out of 13 biopsies, 2 of which were obtained from the same patient over a 5-yearinterval. @*Conclusions@#PLA2R was expressed in a small number of cases diagnosed aspediatricHBV-related MN, indicating that some HBV-related MN cases may beprimary MN concurrent with HBV infection.

The Role of Thymic Stromal Lymphopoietin (TSLP) in Glomerulonephritis

Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like cytokine that is an important trigger and initiator of many allergic diseases. TSLP promotes a T-helper type 2 (Th2) cytokine response that can be pathological. A relationship is formed both at the induction phase of the Th2 response through polarization of dendritic cells to drive Th2 cell differentiation and at the effector phase of the response, by promoting the expansion of activated T cells and their secretion of Th2 cytokines and TSLP. In transgenic mice with TSLP overexpression, it has been reported that TSLP leads to the development of mixed cryoglobulinemic membranoproliferative glomerulonephritis. In addition, TSLP can play an important role in the pathogenesis of IgA nephropathy and systemic lupus erythematosus-related nephritis. From our knowledge of the role of TSLP in the kidney, further studies including the discovery of new therapies need to be considered based on the relationship between TSLP and glomerulonephritis.

Interleukin-13 Increases Podocyte Apoptosis in Cultured Human Podocytes

PURPOSE: Podocytes are important architectures that maintain the crucial roles of glomerular filtration barrier functions. Despite this structural importance, however, the mechanisms of the changes in podocytes that can be an important pathogenesis of minimal change nephrotic syndrome (MCNS) are not clear yet. The aim of this study was to investigate whether apoptosis is induced by interleukin (IL)-13 in cultured human podocytes. METHODS: Human podocytes were treated with different IL-13 doses and apoptotic cells were analyzed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL assay) and fluorescence-activated cell sorting (FACS). RESULTS: The IL-13 increased the number of TUNEL-positive cells in a dose-dependent manner at 6 and 18 hours (P<0.05 and P<0.05, respectively). The apoptosis rate was appeared to be increased slightly in the IL-13-stimulated podocytes (8.63%, 13.02%, and 14.46%; 3, 10 and 30 ng/mL, respectively) than in the control cells (7.66%) at 12 hours by FACS assay. CONCLUSION: Our study revealed that IL-13 expression may increase podocyte apoptosis. Blocking the IL-13 signal pathway can potentially play an important role in regulating the apoptosis of podocytes.

A Successfully Treated Case of Recurrent Focal Segmental Glomerulosclerosis (FSGS) with Plasmapheresis and High dose Methylprednisolone Pulse Therapy

Focal segmental glomerulosclerosis (FSGS) in children, which is a kind of nephrotic syndrome showing steroid resistance, usually progresses to a substantial number of end stage renal disease (ESRD). Although the pathogenesis of primary FSGS is unclear, several recent studies have reported that FSGS is associated with circulating immune factors such as soluble urokinase-type plasminogen activator receptor (suPAR) or anti-CD40 autoantibody. We report a successfully treated case of a 19-year-old female patient who experienced a recurrence of primary FSGS. After the diagnosis of FSGS, the patient progressed to ESRD and received a kidney transplantation (KT). Three days later, recurrence was suspected through proteinuria and hypoalbuminemia. She has been performed plasmapheresis and high dose methylprednisolone pulse therapy and shown remission status without increasing proteinuria for four years after KT. In conclusion, strong immunosuppressive therapy may be helpful for a good prognosis of recurrent FSGS, suppressing several immunologic circulating factors related disease pathogenesis.

Therapeutic Plasma Exchange in Pediatric Kidney Disease: 23-year Experience at the Severance Children's Hospital in Korea

PURPOSE: The American Society for Apheresis provides clinical guidelines for therapeutic apheresis in adults, but there are no guidelines for children. This study aimed to analyze the effect of therapeutic plasma exchange (TPE) in pediatric patients with various kidney diseases in Korea. METHODS: We retrospectively reviewed the data of 16 children (up to 18 years of age) who were admitted to Severance Children's Hospital with refractory kidney disease. All patients received TPE between 1994 and 2016. Clinical and laboratory characteristics such as age, weight, sex, change in blood urea nitrogen (BUN), and creatinine level before and after TPE, and complications after TPE were analyzed. RESULTS: The mean age and weight of the 16 patients at the time of TPE was 11.3±4.0 years and 34.6±17.5 kg, respectively. The BUN level was 35.4 mg/dL before TPE and significantly decreased to 21.5 mg/dL (P=0.025) at 1 week and 20.5 mg/dL (P=0.01) at 1 month after TPE. The creatinine level significantly decreased from 1.20 mg/dL before TPE to 0.90 mg/dL (P=0.02) at 1 week after TPE. Four complications (hypovolemia, anemia, hypocalcemia, and thrombocytopenia) were reported, but were not fatal. CONCLUSION: Our findings suggest that TPE is an effective therapeutic modality in children with refractory kidney disease and can be indicated for the treatment of various kidney diseases.

Therapeutic Plasma Exchange in Pediatric Kidney Disease: 23-year Experience at the Severance Children's Hospital in Korea

PURPOSE: The American Society for Apheresis provides clinical guidelines for therapeutic apheresis in adults, but there are no guidelines for children. This study aimed to analyze the effect of therapeutic plasma exchange (TPE) in pediatric patients with various kidney diseases in Korea. METHODS: We retrospectively reviewed the data of 16 children (up to 18 years of age) who were admitted to Severance Children's Hospital with refractory kidney disease. All patients received TPE between 1994 and 2016. Clinical and laboratory characteristics such as age, weight, sex, change in blood urea nitrogen (BUN), and creatinine level before and after TPE, and complications after TPE were analyzed. RESULTS: The mean age and weight of the 16 patients at the time of TPE was 11.3±4.0 years and 34.6±17.5 kg, respectively. The BUN level was 35.4 mg/dL before TPE and significantly decreased to 21.5 mg/dL (P=0.025) at 1 week and 20.5 mg/dL (P=0.01) at 1 month after TPE. The creatinine level significantly decreased from 1.20 mg/dL before TPE to 0.90 mg/dL (P=0.02) at 1 week after TPE. Four complications (hypovolemia, anemia, hypocalcemia, and thrombocytopenia) were reported, but were not fatal. CONCLUSION: Our findings suggest that TPE is an effective therapeutic modality in children with refractory kidney disease and can be indicated for the treatment of various kidney diseases.