Sodium removal per ultrafiltration volume in automated peritoneal dialysis in pediatric patients.

BACKGROUND: The standard rate of sodium removal in adult anuric patients on continuous ambulatory peritoneal dialysis (CAPD) is 7.5 g/L of ultrafiltration volume (UFV). Although automated PD (APD) is widely used in pediatric patients, no attempt has yet been made to estimate sodium removal in APD. METHODS: The present, retrospective cohort study included pediatric patients with APD who were managed at Tokyo Metropolitan Children's Medical Center between July 2010 and November 2017. The patients underwent a peritoneal equilibrium test (PET) at our hospital. Sodium removal per UFV was calculated by peritoneal function and dwell time using samples from patients on APD with 1- and 2-h dwell effluent within three months of PET and 4- and 10-h dwell effluent at PET. RESULTS: In total, 217 samples from 18 patients were included, with 63, 81, and 73 of the samples corresponding to the High [H], High-average [HA], and Low-average [LA] PET category, respectively. Sodium removal per UFV (g/L in salt equivalent) for dwell times of one, two, four, and ten hours was 5.2, 8.8, 8.0, and 11.5 for PET [H], 5.3, 5.8, 5.6, and 8.1 for PET [HA], and 4.6, 5.1, 5.1, and 7.1 for PET [LA], respectively. CONCLUSIONS: Sodium removal per UFV in pediatric APD was less than the standard adult CAPD and tended to be lower with shorter dwell times, leading to sodium accumulation. Therefore, salt intake should be restricted in combination with one or more long daytime dwells, especially in anuric patients.

Joint Fluid Cell Count in Acute Bacterial Arthritis Patients Proven Positive Culture in Children.

BACKGROUND: Acute bacterial arthritis (ABA) is a serious, pediatric infection that can result in motor comorbidities. Normally, a joint fluid white blood cell (WBC) count of 50,000 or more cells/mm 3 is used to make a presumptive diagnosis of ABA. This study evaluated the utility of the joint fluid WBC count for diagnosing pediatric ABA confirmed by a positive culture result. METHODS: Patients with ABA between March 2010 and March 2023 at Tokyo Metropolitan Children's Medical Center were included. ABA was confirmed by positive joint fluid culture results for a pathogenic organism. Patients with negative results and those without a joint fluid WBC count were excluded. Electronic medical records were retrospectively reviewed for demographic data, timing of arthrocentesis, culture results and the joint fluid WBC count. RESULTS: Ninety-five patients with ABA were identified; of these, 22 were included. The median age was 5 years [interquartile range (IQR): 2-10 years]. Males comprised 55% of the population. The median joint fluid WBC count was 19,575 (IQR: 6806-47,388) cells/mm 3 , and 23% of the patients had 50,000 cells/mm 3 or more. The median time from symptom onset to arthrocentesis was 3 days (IQR: 2-5 days). The isolated organisms were methicillin-susceptible Staphylococcus aureus (50%), methicillin-resistant S. aureus (9%), Streptococcus pyogenes (27%), Streptococcus pneumoniae (5%), Klebsiella pneumoniae (5%) and Salmonella spp. (5%). CONCLUSIONS: Most of the patients with ABA confirmed by positive results of a joint fluid culture had a joint fluid WBC count of less than 50,000 cells/mm 3 .

A Case of Unilateral Renal Agenesis Detected by Abdominal Point-Of-Care Ultrasound.

As the interest in point-of-care ultrasound (POCUS) for investigating pediatric abdominal emergencies has been growing, an increasing number of literatures about abdominal POCUS has been published. We describe a noteworthy instance of a systematic approach using abdominal POCUS for detecting unilateral renal agenesis (URA) in previously healthy children with suspected intussusception. A previously healthy three-year-old girl was brought to our emergency department (ED) due to abdominal pain and bloody diarrhea. POCUS was performed to investigate the presence of intussusception. POCUS was able to rule out intussusception and detect URA. The investigation led the patient to a proper nephrology follow-up. When performing abdominal POCUS to evaluate gastrointestinal pathologies, it is important to pay attention to concomitant congenital anomalies of the kidney and urinary tract (CAKUT).

Fractional excretion of total protein in patients with nephrotic syndrome.

BACKGROUND: The urine protein to creatinine ratio (UPCR) correlates well with the 24-h urine protein test (24-h UPT) and is a reliable indicator of proteinuria. However, in nephrotic syndrome, the correlation between the UPCR and the 24-h UPT tends to decrease. To address this, we introduced the fractional excretion of total protein (FETP), which reflects serum total protein and creatinine levels because severe hypoproteinemia and/or elevated serum creatinine levels tend to occur under these conditions. The 24-h UPT corrected for body surface area (BSA) (24-h UPT/BSA) was used to take body size into consideration. The correlation coefficients for 24-h UPT/BSA and FETP and 24-h UPT/BSA and UPCR were calculated. The statistical significance of the differences between these coefficients was also calculated. METHODS: Thirty-six pediatric patients with nephrotic syndrome were included in this study. The FETP was calculated as total protein clearance/creatinine clearance (%). Correlation coefficients were calculated for 24-h UPT/BSA and FETP and 24-h UPT/BSA and UPCR. The statistical significance of the differences between these coefficients was also calculated. RESULTS: The mean ± standard error of FETP was 0.11% ± 0.013%. The correlation coefficients of FETP and UPCR with 24-h UPT/BSA were 0.91 and 0.81, respectively. The FETP demonstrated a significantly stronger correlation with 24-h UPT/BSA than with UPCR (p = 0.01). CONCLUSIONS: The FETP correlated more strongly with 24-h UPT/BSA than with UPCR in patients with nephrotic syndrome. The FETP is a reliable indicator of proteinuria in nephrotic syndrome, especially in patients with severe hypoproteinemia or elevated serum creatinine levels.

Proportion of Successful Lumbar Punctures in Infants Younger Than Three Months.

It is important to perform lumbar punctures (LPs) without a single traumatic tap in infants younger than three months owing to the risk of serious complications. The proportion of LPs in which clear cerebrospinal fluid (CSF) was obtained has been previously reported, but some of the procedures involved a traumatic tap. The present study aimed to identify the proportion of LPs in which clear CSF was obtained without a single traumatic tap and the factors associated with successful LPs in infants younger than three months. This retrospective, observational study included children younger than three months who underwent an LP in the pediatric emergency department between April 2018 and March 2021. The primary outcome was the proportion of successful LPs, defined as LPs obtaining clear CSF without a single traumatic tap. Multiple logistic regression analysis was used to identify factors related to successful LPs. Of 126 eligible patients, 121 were included. Among these, 83 (69%) were in the successful group. No factors significantly associated with successful LPs were found. Larger studies based on an accurate definition of successful LPs, such as that provided by this study, are needed to investigate related factors to increase the rate of successful LPs in this age group.

Combined usage of serodiagnosis and O antigen typing to isolate Shiga toxin-producing Escherichia coli O76:H7 from a hemolytic uremic syndrome case and genomic insights from the isolate.

IMPORTANCE: Hemolytic uremic syndrome (HUS) is a life-threatening disease caused by Shiga toxin-producing Escherichia coli (STEC) infection. The treatment approaches for STEC-mediated typical HUS and atypical HUS differ, underscoring the importance of rapid and accurate diagnosis. However, specific detection methods for STECs other than major serogroups, such as O157, O26, and O111, are limited. This study focuses on the utility of PCR-based O-serotyping, serum agglutination tests utilizing antibodies against the identified Og type, and isolation techniques employing antibody-conjugated immunomagnetic beads for STEC isolation. By employing these methods, we successfully isolated a STEC strain of a minor serotype, O76:H7, from a HUS patient.

Treatment Delay of Febrile Urinary Tract Infections Among Infants With Respiratory Symptoms.

OBJECTIVE: To evaluate whether antibiotic treatment of febrile urinary tract infection (UTI) is delayed in febrile infants with respiratory symptoms compared with those without. STUDY DESIGN: Data of infants 2-24 months of age diagnosed with UTI from March 1, 2012 to May 31, 2023 were collected from our hospital's medical charts and triage records. Patients with known congenital anomalies of the kidney and urinary tract or a history of febrile UTI were excluded. Patients were classified as having respiratory symptoms if they had any of the following symptoms or clinical signs: cough, rhinorrhea, pharyngeal hyperemia and otitis media. Time to first antibiotic treatment from fever onset was compared between patients with and without respiratory symptoms. A Cox regression model was constructed to adjust for potential confounders. RESULTS: A total of 214 patients were eligible for analysis. The median age of the eligible patients was 5.0 months (interquartile range: 3.0-8.8) and 118 (55%) were male. There were 104 and 110 patients in the respiratory symptom and no respiratory symptom groups, respectively. The time to first antibiotic treatment was significantly longer in the group with respiratory symptoms (51 hours vs. 21 hours). Respiratory symptoms were significantly associated with a longer time to first treatment after adjustment for age and sex in the Cox regression model (hazard ratio = 0.63, 95% confidence interval: 0.47-0.84). CONCLUSIONS: Treatment of febrile UTI infants with respiratory symptoms tends to be delayed. Pediatricians should not exclude febrile UTI even in the presence of respiratory symptoms.

Technical requirements and devices available for long-term hemodialysis in children-mind the gap!

Children requiring long-term kidney replacement therapy are a "rare disease" cohort. While the basic technical requirements for hemodialysis (HD) are similar in children and adults, key aspects of the child's cardiovascular anatomy and hemodynamic specifications must be considered. In this article, we describe the technical requirements for long-term HD therapy for children and the devices that are currently available around the world. We highlight the characteristics and major technical shortcomings of permanent central venous catheters, dialyzers, dialysis machines, and software available to clinicians who care for children. We show that currently available HD machines are not equipped with appropriately small circuits and sensitive control mechanisms to perform safe and effective HD in the youngest patients. Manufacturers limit their liability, and health regulatory agencies permit the use of devices, only in children according to the manufacturers' pre-specified weight limitations. Although registries show that 6-23% of children starting long-term HD weigh less than 15 kg, currently, there is only one long-term HD device that is cleared for use in children weighing 10 to 15 kg and none is available and labelled for use in children weighing less than 10 kg anywhere in the world. Thus, many children are being treated "off-label" and are subject to interventions delivered by medical devices that lack pediatric safety and efficacy data. Moreover, recent improvements in dialysis technology offered to adult patients are denied to most children. We, in turn, advocate for concerted action by pediatric nephrologists, industry, and health regulatory agencies to increase the development of dedicated HD machines and equipment for children.

Association of Yersinia Infection With Kawasaki Disease: A Prospective Multicenter Cohort Study.

BACKGROUND: Yersinia infection is known to present with Kawasaki disease (KD)-like symptoms although differentiating the 2 has been a challenge. The present study aimed to describe the clinical characteristics and prevalence of Yersinia infection presenting with KD-like symptoms. METHODS: The present, prospective, multicenter study enrolled patients who received a diagnosis of KD between January 2021 and January 2022 at 2 hospitals in Tokyo. Stool samples were collected within 3 days of the start of KD treatment, and cultures were performed for Yersinia . Clinical history and symptoms suggestive of Yersinia infection were also evaluated. RESULTS: During the study period, 141 KD patients were screened and 117 patients with evaluable stool samples were registered. Only 1 patient was positive for Yersinia pseudotuberculosis , which was detected from both stool and blood cultures. The patient was refractory to KD treatment but improved after initiation of appropriate antibiotic therapy. CONCLUSIONS: Routine screening for Yersinia is not appropriate for patients with KD and should be limited to certain patients in high-risk areas and those who are refractory to the standard KD treatment.

Clinical implications of gallbladder enlargement in Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) presents with gallbladder enlargement (GBE) or hydrops in the acute phase. Although GBE is highly specific to KD, epidemiological data on GBE have not been updated. In this study we evaluated the occurrence rate of GBE in KD and characterized the clinical features of patients who developed GBE. METHODS: The present study was a prospective, observational study. The maximum longitudinal area of the gallbladder and the common bile duct diameter in KD patients were measured by ultrasonography at the start of initial intravenous immunoglobulin (IVIG) therapy (day 0) and on days 7, 30, and 60 of therapy. The primary outcome was the complication rate of GBE (z- score ≥2.0) on day 0. The secondary outcome was the association of GBE with cholestasis, unresponsiveness to IVIG, and coronary artery lesions (CAL). RESULTS: Gallbladder enlargement occurred in 35% (35/101) of patients on day 0. Cholestasis and severe patients (Kobayashi score [KS] ≥5) were more common in the GBE group (20.6% vs. 1.6%, p = 0.002, and 54.3% vs. 15.2%, p < 0.001, respectively). In patients with a KS of ≤4, the non-responder rate was higher in the GBE group (44% vs. 20%, p = 0.0495) but did not differ in those with a KS of ≥5 (21% vs. 20%, p = 0.95). The rate of CAL occurrence did not differ significantly between the groups (8.6% vs. 6.1%, p = 0.64). CONCLUSIONS: Gallbladder enlargement occurred in 35% of KD patients and was associated with cholestasis. Gallbladder enlargement may not only be a diagnostic finding, but also a severity marker in KD patients.

Viral loads of parainfluenza virus type 3 and severity of respiratory diseases in children.

BACKGROUND: Parainfluenza virus type 3 (PIV-3) is one of the common pathogens for respiratory infections in children. Whether viral load of PIV-3 is associated with severity of respiratory diseases in children is not yet known. Our aim was to determine significance of PIV-3 viral load among infected children. METHODS: We conducted a single-center, retrospective study at Tokyo Metropolitan. Children's Medical Center, Japan, from June to August 2021. Hospitalized children were screened with a posterior nasal swab for multiplex PCR, and viral load was subsequently measured from remained samples by real-time PCR. Demographic data were collected from digital charts. PIV-3 positive patients were categorized into mild group with no oxygen demand, moderate group with low-flow oxygen demand and severe group with high-flow nasal cannula oxygen or non-invasive positive pressure ventilation or mechanical ventilation. Viral loads were compared among mild, moderate and severe groups. RESULTS: 151 patients were positive for PIV-3. We found no statistically significant association among PIV-3 viral load and severity of respiratory diseases (p = 0.35), and no statistically significant association between severity of illness and co-detection of other viruses. In each severity group, relatively high viral load per posterior nasal swab was observed at the time of testing. CONCLUSION: Among PIV-3 patients, we could not find statistically significant between viral load and their severity, therefore we could not conclude that viral load is a good surrogate marker for clinical severity of PIV-3.

Eculizumab for paediatric patients with atypical haemolytic uraemic syndrome: full dataset analysis of post-marketing surveillance in Japan.

BACKGROUND: Eculizumab was approved for atypical haemolytic uraemic syndrome (aHUS) in Japan in 2013. Post-marketing surveillance (PMS) was mandated by regulatory authorities to assess the safety and effectiveness of eculizumab in patients with aHUS in a real-world setting. METHODS: Paediatric patients in the PMS cohort who were <18 years of age at the first administration of eculizumab and diagnosed with aHUS [excluding Shiga toxin-producing Escherichia coli HUS, thrombotic thrombocytopaenic purpura and secondary thrombotic microangiopathy (TMA)] were included in the effectiveness and safety analysis. Clinical endpoints of effectiveness [complete TMA response, TMA event-free status, platelet (PLT) count and lactate dehydrogenase (LDH) normalization, serum creatinine (sCr) decrease and estimated glomerular filtration rate (eGFR) improvement] were analysed in patients treated with at least one dose of eculizumab. Serious adverse events (SAEs) were also evaluated. RESULTS: A total of 40 paediatric patients (median age 5 years) were included. The median eculizumab treatment duration was 66 weeks. PLT count, LDH and eGFR significantly improved at 10 days post-treatment. Complete TMA response, haematologic normalization, sCr decrease, eGFR improvement and TMA event-free status were achieved by 73.3%, 73.3%, 70.0%, 78.3% and 77.5% of patients, respectively. Discontinuation criteria were met by 18 patients: 13 patients maintained treatment discontinuation at the end of observation and 5 patients, including 1 patient with aHUS relapse, continued the treatment but extended the treatment interval. During eculizumab treatment, 59 SAEs (0.66/person-year) were reported. Although four deaths were reported, none of them were related to eculizumab. CONCLUSION: Eculizumab was well tolerated and effective for paediatric patients with aHUS in the real-world setting in Japan.

Different Clinical Courses of Nephronophthisis in Dizygotic Twins.

Siblings with nephronophthisis occasionally show different clinical courses; however, the reasons for this remain unclear. We herein report cases of nephronophthisis in a pair of dizygotic twins with different clinical courses. The brother developed end-stage kidney disease at 17 years old; however, his sister did not show kidney insufficiency. Kidney biopsies revealed severe tubulointerstitial damage at 14 and 22 years old in the brother and sister, respectively. Both had a homozygous NPHP1 deletion with different heterozygous mutations related to hereditary cystic kidney disease. Since the dizygotic twins were exposed to similar environmental factors, genetic factors may have influenced their clinical course more strongly than environmental factors.

Factors related to ultrafiltration volume with icodextrin dialysate use in children.

BACKGROUND: Icodextrin has a lower absorption rate, and icodextrin peritoneal dialysate contributes to more water removal than glucose dialysate in patients with high peritoneal permeability. There are limited data on icodextrin dialysate use in children. METHODS: This study included all pediatric patients who received peritoneal equilibration tests and peritoneal dialysis with icodextrin dialysate at the study center. The factors related to ultrafiltration volume with icodextrin dialysate with long dwell time were statistically analyzed. Then the ultrafiltration volume with icodextrin and medium-concentration glucose dialysate was compared in individual cycles in the same patients. RESULTS: Thirty-six samples were included in the icodextrin group, and nine samples were used to compare the ultrafiltration volume with icodextrin and glucose dialysate. Dwell time, D/P-creatinine, D/D0-glucose, age, height, and weight correlated significantly with the ultrafiltration volume of icodextrin dialysate (p < 0.05). A dwell volume equal to or more than 550 mL/m2 was associated with a significantly higher ultrafiltration volume than a lower dwell volume (p = 0.039). Multiple regression analysis revealed that dwell time (p = 0.038) and height (p < 0.01) correlated with ultrafiltration volume significantly. In addition, the ultrafiltration volume was superior (p < 0.01), and dwell time was longer (p = 0.02), with icodextrin dialysate than with medium-concentration glucose dialysate. CONCLUSIONS: The ultrafiltration volume with icodextrin dialysate decreases in patients with small stature. Providing sufficient dwell time and volume is important for maximal water removal even in children. Ultrafiltration volume is superior with icodextrin than medium-concentration glucose dialysate for long dwell times. A higher resolution version of the Graphical abstract is available as Supplementary information.