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Background/purpose: Congenital nephrotic syndrome (CNS) is one of the important causes of end-stage kidney disease in children. Studies on the genotype, phenotype, and clinical outcome in infants with CNS caused by genetic mutations are scarce., Methods: We analyzed the genetic background, clinical manifestations, treatment response, and prognosis of pediatric patients with CNS in Taiwan., Results: Fifteen infants with CNS were enrolled, and 11 patients of median age 21 (interquartile range 3∼44) days caused by genetic mutations from 10 unrelated families were included in the study. Of the eleven patients, 9 had extra-renal manifestations including microcephaly, facial dysmorphism, and skeletal anomalies. More than two-thirds of the patients had disease onset before 1 month of age. Diffuse meningeal sclerosis was the most common histological characteristic. Whole exome sequencing followed by direct Sanger sequence revealed mutations in OSGEP (R247Q), WT1 (R366H and R467Q), LAMB2 (Q1209∗ and c. 5432-5451 19 bp deletion), NUP93 (D302V), and LAGE3 (c.188+1G > A). Three of the variants were novel. Corticosteroids and/or immunosuppressants were administered in 2 patients, but both were refractory to treatment. During the mean 3.5 years of follow-up, all but two died of uremia and sepsis. The two survivors reached end-stage kidney disease and required peritoneal dialysis, and one of them underwent uneventful renal transplantation., Conclusion: The majority of patients with CNS in Taiwan were caused by OSGEP followed by WT1 mutation. R247Q is the hotspot mutation of OSGEP in Taiwan. CNS patients in Taiwan suffer from significant morbidity and mortality., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background/purpose: We investigated the diagnostic performance of the anal sphincter relaxation integral (ASRI) for infants with Hirschsprung's disease (HD)., Methods: We performed water-perfused high-resolution anorectal manometry (HRAM) in 18 infants (9 with HD), and solid-state HRAM in another 18 infants (4 with HD). We calculated the ASRI during the rectoanal inhibitory reflex (RAIR) maneuver at pressure cutoffs of <10 mmHg (ASRI 10) and <15 mmHg (ASRI 15). We investigated the diagnostic performance of the ASRI for HD in infants undergoing water-perfused and solid-state HRAM., Results: HD infants who underwent either water-perfused or solid-state HRAM had significantly lower ASRI 10 and ASRI 15 values, compared with non-HD infants (P < 0.05 and P < 0.05, respectively). Using the water-perfused HRAM system, ASRI 10 and ASRI 15 values of <7 and <29 mmHg s.cm, respectively, exhibited good diagnostic performance for HD (88.89% and 88.89%, respectively). Receiver operating characteristic curve analysis indicated that ASRI 10 and ASRI 15 values of <5.5 and <20 mmHg s.cm, respectively, were optimal for the diagnosis of HD infants when using the solid-state HRAM system, with high diagnostic accuracies of 83.33% and 83.33%, respectively., Conclusion: ASRI may assist the diagnosis of HD infants using either water-perfused or solid-state HRAM. These systems require different catheter-specific ASRI cutoffs for the prediction of HD., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Cases of glomerulopathy after COVID-19 vaccination have been reported in the adult population, while only a few cases have been reported in children and adolescents. For better understanding of this association in pediatric population, we aimed to describe clinical course of patients with glomerulopathy within 60 days of COVID-19 vaccination who were under followed up in the pediatric nephrology department of National Taiwan University Children's Hospital., Methods: We reviewed the clinical characteristics, vaccine types, and outcomes of patients with newly diagnosed glomerular diseases or relapse of underlying glomerulopathy within 60 days after COVID-19 vaccination at our facility between January 2021 and July 2022., Results: Thirteen pediatric patients were found to have newly diagnosed glomerular diseases or relapse from their underlying glomerulopathy after receiving their first, second, or third COVID-19 vaccines in our facility. Of the five pediatric patients with newly diagnosed glomerulopathy after vaccination, thin basement membrane nephropathy, idiopathic nephrotic syndrome, and hematuria have been identified. Seven patients had relapse episodes of underlying nephrotic syndrome and one patient with underlying isolated microscopic hematuria developed subnephrotic proteinuria after COVID-19 vaccination. All patients experienced remission or improvement with either immunosuppressive or conservative treatment during the follow-up period., Conclusions: This is the largest case series to date of pediatric glomerulopathy after COVID-19 vaccination. From our report, patients with either newly diagnosed or relapse of glomerulopathy after vaccination had good outcomes, and receiving vaccination to prevent COVID-19 infection or complications should be encouraged in pandemic era under close monitoring kidney manifestations., Competing Interests: Conflict of interests The authors declare no conflicts of interest., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Atypical hemolytic uremic syndrome (aHUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, is a rare but life-threatening systemic disorder caused by the dysregulation of the complement pathway. Current advances in molecular analysis and pathogenesis have facilitated the establishment of diagnosis and development of effective complement blockade. Based on this recent consensus, we provide suggestions regarding the diagnosis and management of aHUS in Taiwan. The diagnosis of aHUS is made by the presence of TMA with normal ADAMTS13 activity without known secondary causes. Although only 60% of patients with aHUS have mutations in genes involving the compliment and coagulation systems, molecular analysis is suggestive for helping establish diagnosis, clarifying the underlying pathophysiology, guiding the treatment decision-making, predicting the prognosis, and deciding renal transplantation. Complement blockade, anti-C5 monoclonal antibody, is the first-line therapy for patients with aHUS. Plasma therapy should be considered for removing autoantibody in patients with atypical HUS caused by anti-CFH or complement inhibitor is unavailable., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

We present the case of a 6-year-old Taiwanese boy with a fulminant course of COVID-19 manifesting as high fever, acute consciousness changes, and status epilepticus. Brain MRI showed restricted diffusion in the bilateral hemisphere. Electroencephalogram showed diffuse slow waves with few spikes. CSF study was clear without evidence of common pathogens. He received treatment with antiviral agents, corticosteroids, intravenous immunoglobulins, and anti-IL-6 monoclonal antibodies. However, progressive fulminant hepatitis, hyperammonaemia, and disseminated intravascular coagulopathy developed. Rescue therapy with hybrid continuous renal replacement therapy and plasma exchange were performed in the first 11 days. The patient improved and was extubated on the 11th day. After physical therapy, his neurological function improved significantly. The patient was discharged under rehabilitation after 1 month of hospitalization. Viral sequencing confirmed infection with the Omicron BA.2.3 variant, one of the dominant strains in Taiwan and Hong Kong. Whole-exome sequencing revealed heterozygous uncertain significance variants in TICAM-1, RNF 31, and mitochondrial MT-RNR1, which provide additional support for the fulminant course. To the best of our knowledge, this is the first reported case of COVID-19 in a child with a fulminant course of acute encephalitis and hepatitis who successfully recovered by hybrid continuous renal replacement therapy and plasma exchange., (Copyright © 2023. Published by Elsevier B.V.)

Background: Acute kidney injury (AKI) is the most frequent complication in critically ill neonatal and pediatric patients receiving extracorporeal membrane oxygenation (ECMO) support. This study analyzed risk factors for in-hospital mortality and the incidence of AKI in neonatal and pediatric patients received ECMO support., Methods: We reviewed the medical records of 105 neonatal and 171 pediatric patients who received ECMO support at the intensive care unit (ICU) of a tertiary care university hospital between January 2008 and December 2015. Demographic, clinical, and laboratory data were retrospectively collected as survival and AKI predictors, utilizing the Kidney Disease Improving Global Outcome (KDIGO) consensus definition for AKI., Results: In the 105 neonatal and 171 pediatric patients, the overall in-hospital mortality rate were 58% and 55% respectively. The incidence of AKI at post-ECMO 24 h were 64.8% and 61.4%. A greater KDIGO 24-h severity was associated with a higher in-hospital mortality rate (chi-square test; p < 0.01) and decreased survival rate (log-rank tests, p < 0.01). In univariate logistic regression analysis of in-hospital mortality, the CVP level at post ECOMO 24-h increased odds ratio (OR) (OR = 1.27 [1.10-1.46], p = 0.001) of in-hospital mortality in neonatal group; as for pediatric group, elevated lactate (OR = 1.12 [1.03-1.20], p = 0.005) and PT (OR = 1.86 [1.17-2.96], p = 0.009) increased OR of in-hospital mortality. And the KDIGO 24h stage 3 had the strongest association with in-hospital mortality in both neonatal (p = 0.005) and pediatric (p = 0.001) groups. In multivariate OR of neonatal and pediatric groups were 4.38 [1.46-13.16] (p = 0.009) and 3.76 [1.70-8.33] (p = 0.001), respectively., Conclusion: AKI was a significant risk factor for in-hospital mortality in the neonatal and pediatric patients who received ECMO support. A greater KDIGO24-h severity was associated with higher mortality rates and decreased survival rate in both neonatal and pediatric groups. Of note, KDIGO24h can be an easy and early tool for the prognosis of AKI in the neonatal and pediatric patients., Competing Interests: Declaration of competing interest A conflict of interest occurs when an individual's objectivity is potentially compromised by a desire for financial gain, prominence, professional advancement or a successful outcome. JFMA Editors strive to ensure that what is published in the Journal is as balanced, objective and evidence-based as possible. Since it can be difficult to distinguish between an actual conflict of interest and a perceived conflict of interest, the Journal requires authors to disclose all and any potential conflicts of interest., (Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Proteinuria is a common finding in children. It may be due to a benign cause, but it can also represent early renal injury. Of children with persistent proteinuria noted in mass urine screening programs, 35% have a urine protein level greater than 100 mg/dl and many of them are associated with many underlying renal diseases. The aim of this study was to identify the etiology and prognosis of persistent proteinuria in children., Methods: We collected data on urine protein from January 2011 to December 2016 in a tertiary medical center. During this 6-year period, 37,645 children received urinalysis, and 2.3% were found to have persistent proteinuria. We reviewed their medical charts for clinical diagnoses and renal function. According to the level of persistent proteinuria, we divided the children into three groups (mild, moderate, and severe)., Results: Most clinical diagnoses in the mild persistent proteinuria group were not readily identifiable. In the moderate and severe groups, acute kidney injury was the leading cause of significant proteinuria, followed by systemic lupus erythematosus, steroid-sensitive nephrotic syndrome, and congenital urogenital tract anomalies. There were significant differences in the rate of chronic renal insufficiency among the three groups. Prematurity with extremely low birth weight was also a major factor associated with pediatric chronic renal insufficiency., Conclusion: Assessing persistent proteinuria in children is important due to the diverse range of associated diseases or mortality., (Copyright © 2017. Published by Elsevier B.V.)

Background/purpose: The zebrafish (Danio rerio) is a new animal model for cardiac research. Zebrafish possessing a green fluorescent heart facilitates the dynamic observation of cardiac development, morphology, and function in vivo. However, the effect of an excessive expression of green fluorescent protein (GFP) in cardiac muscle on the heart function of zebrafish has not been reported., Methods: We cloned a 1.6 kb polymerase chain reaction (PCR) product containing the upstream sequence (870 bp), exon 1 (39 bp), intron 1 (682 bp), and exon 2 (69 bp) of the zebrafish cardiac myosin light chain 2 gene. A germ line-transmitted zebrafish possessing a green fluorescent heart was generated by injecting this PCR product fused with the GFP gene with ends consisting of inverted terminal repeats of an adeno-associated virus., Results: Green fluorescence was intensively and specifically expressed in the myocardial cells located around both the heart chambers. Two lines with different GFP expression were bred (A26 and A277). The luminance of A277 was brighter than that of A26 (1.7-fold). The 4 days postfertilization (dpf) cardiac function and morphology were similar between these two groups. However, the 8 dpf cardiac growth seemed to be retarded in the A277 group. The 8 dpf heart rate, stroke volume, and cardiac output were also significantly lower in the A277 group., Conclusion: Excess expression of GFP seems to exert some detrimental effects on zebrafish hearts.