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.

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).

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.

Mechanical analysis of the improved superelastic Ni-Ti alloy wire using the orthodontic simulator with high-precision sensors.

PURPOSE: The authors have been using improved superelastic Nickel-Titanium alloy wire (ISW) to close and align extraction spaces simultaneously, instead of separately using rigid wires for closing extraction spaces and Ni-Ti alloy wires for leveling and aligning. ISW has a low stiffness, which makes it challenging to generate sufficient moments. This study aimed to demonstrate the forces and moments exerted on adjacent brackets using an orthodontic simulator (OSIM) attached to a high-precision 6-axis sensor. MATERIALS AND METHODS: In experiment 1, a 0.016 × 0.022-inch ISW, stainless steel (SS) wire, and ß-titanium wires were ligatured into the two brackets. The 0.018 × 0.025-inch slot self-ligating brackets were bonded to two simulated teeth at the same height, and the experiment was conducted using the high-precision OSIM. The distance between the brackets was 10 mm, the V-bend angles of the installed wires were 10°, 20°, 30°, and 40°, and the apex position was set at the center of the bracket. In experiment 2, 6.0- and 9.0-mm long elastomeric chains were placed on the same brackets as in Experiment 1 to measure forces and moments. The distance between the brackets was increased by 1.0 mm from 6.0 to 15.0 mm. Both experiments were conducted in a 37 °C thermostatic chamber similar to the oral environment. RESULTS AND DISCUSSION: In experiment 1, we measured moments on both sides for all the wires. As the V-bend angle increased, the absolute values of the moments also increased. With a V-bend angle of 10°, there was a significant (p < 0.05) difference in the moment generated in the left and right brackets among the three wire types. In the ISW, -1.67 ± 0.38 N・mm was generated in the left bracket, while 0.38 ± 0.26 N・mm was generated in the right bracket at 10°. At 20°, -1.77 ± 0.69 N・mm was generated in the left bracket, while 2.37 ± 0.94 N・mm was generated in the right bracket. At 30°, -2.98 ± 0.49 N・mm was generated in the left bracket, while 3.25 ± 0.32 N・mm was generated in the right bracket. Moreover, at 40°, -3.96 ± 0.58 N・mm was generated in the left bracket, while 3.55 ± 0.53 N・mm was generated in the right bracket. Furthermore, in experiment 2, the moments increased in proportion to the increase in distance between the centers of the two brackets. Absolute values of the moments were approximately equal for the left and right brackets. The 6.0-mm elastomeric chain generated a minimum force of -0.09 ± 0.05 N in the left direction when the distance between brackets was 6.0 mm, while a maximum of 1.24 ± 0.3 N when the distance between brackets was 12 mm in the right bracket. In the left bracket, minimum and maximum forces of -0.09 ± 0.07 and 1.3 ± 0.4 N were generated in the right direction, respectively. The 9.0-mm elastomeric chain generated a minimum force of 0.03 ± 0.07 N in the left direction when the distance between brackets was 9.0 mm, while a maximum of 1.3 ± 0.1 N when the distance between brackets was 15 mm in the right bracket. In the left bracket, minimum and maximum forces of 0.05 ± 0.06 and 0.98 ± 0.2 N were generated in the right direction, respectively. CONCLUSION: Mechanical data of the ISW have been collected in the study, which was previously difficult to perform owing to the low stiffness of the wire. It is suggested that the ISW can provide sufficient moments with the addition of V-bends to close the space by bodily movement.

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.

A Novel Mouse Model of Idiopathic Nephrotic Syndrome Induced by Immunization with the Podocyte Protein Crb2.

BACKGROUND: The cause of podocyte injury in idiopathic nephrotic syndrome (INS) remains unknown. Although recent evidence points to the role of B cells and autoimmunity, the lack of animal models mediated by autoimmunity limits further research. We aimed to establish a mouse model mimicking human INS by immunizing mice with Crb2, a transmembrane protein expressed at the podocyte foot process. METHODS: C3H/HeN mice were immunized with the recombinant extracellular domain of mouse Crb2. Serum anti-Crb2 antibody, urine protein-to-creatinine ratio, and kidney histology were studied. For signaling studies, a Crb2-expressing mouse podocyte line was incubated with anti-Crb2 antibody. RESULTS: Serum anti-Crb2 autoantibodies and significant proteinuria were detected 4 weeks after the first immunization. The proteinuria reached nephrotic range at 9-13 weeks and persisted up to 29 weeks. Initial kidney histology resembled minimal change disease in humans, and immunofluorescence staining showed delicate punctate IgG staining in the glomerulus, which colocalized with Crb2 at the podocyte foot process. A subset of mice developed features resembling FSGS after 18 weeks. In glomeruli of immunized mice and in Crb2-expressing podocytes incubated with anti-Crb2 antibody, phosphorylation of ezrin, which connects Crb2 to the cytoskeleton, increased, accompanied by altered Crb2 localization and actin distribution. CONCLUSION: The results highlight the causative role of anti-Crb2 autoantibody in podocyte injury in mice. Crb2 immunization could be a useful model to study the immunologic pathogenesis of human INS, and may support the role of autoimmunity against podocyte proteins in INS.

USP40 deubiquitinates HINT1 and stabilizes p53 in podocyte damage.

Podocyte damage is a major pathological lesion leading to focal segmental glomerulosclerosis (FSGS). Podocytes damaged by cellular stress undergo hypertrophy to compensate for podocytopenia. It is known that cyclin-dependent kinase inhibitors induced by p53 ensure podocytes hypertrophy; however, its precise mechanism remains to be further investigated. In this study, we found that ubiquitin specific protease 40 (USP40) is a novel regulator of p53. Although USP40 knockout mice established in the present study revealed no abnormal kidney phenotype, intermediate filament Nestin was upregulated in the glomeruli, and was bound to and colocalized with USP40. We also found that USP40 deubiquitinated histidine triad nucleotide-binding protein 1 (HINT1), an inducer of p53. Gene knockdown experiments of USP40 in cultured podocytes revealed the reduction of HINT1 and p53 protein expression. Finally, in glomerular podocytes of mouse FSGS, upregulation of HINT1 occurred in advance of the proteinuria, which was followed by upregulation of USP40, p53 and Nestin. In conclusion, USP40 bound to Nestin deubiquitinates HINT1, and in consequence upregulates p53. These results provide additional insight into the pathological mechanism of podocyte hypertrophy in FSGS.

Half of children with IgA vasculitis-associated nephritis with nephrotic state spontaneously recover.

BACKGROUND: The clinical spectrum of Henoch-Schönlein purpura nephritis (HSPN), now known as IgA vasculitis-associated nephritis (IgAVN), ranges from isolated microscopic haematuria to nephrotic syndrome, progressive glomerulonephritis, and kidney failure. The outcome also varies, and the management of IgAVN is controversial. The presence of nephrotic state at disease onset is thought to be a risk factor of a poor prognosis. However, not all patients with nephrotic state have a poor prognosis, and it is unclear whether they need early treatment. METHODS: We herein retrospectively examined the clinical course of paediatric IgAVN cases with nephrotic state (serum albumin [sAlb]<3.0 g/dL and urine protein-creatinine ratio of >2.0 g/ gCr) without kidney injury treated at our hospital between 2010 and 2018. RESULTS: Of the 216 patients with IgAVN identified, 17 met the inclusion criteria. The median follow-up period from disease onset to the last observation was 40.5 months (IQR:31.0-74.2). Eleven patients were male, the median age at onset was 5 years, the minimum serum Alb level was 1.9 g/dL, the maximum proteinuria value was 12.3 g/gCr, and the median minimum eGFR was 86.0 mL/min/1.73 m2 in the acute phase. Eight patients (47%) achieved resolution of nephrotic state within 3 months and complete remission without treatment by the last observation. The patients with spontaneous resolution of nephrotic state had less severe hypoalbuminaemia (Alb<2.0 g/dL) and tended to show a quick increase in the serum albumin level. CONCLUSIONS: Our study found that half of paediatric patients with IgAVN with nephrotic state achieved spontaneous resolution without treatment and enjoyed a favourable short-term outcome. Consideration of the duration of nephrotic state and trends in the serum albumin level in children with IgAVN may allow unnecessary kidney biopsies and immunosuppressive therapy to be avoided.

Perinatal factors contributing to chronic kidney disease in a cohort of Japanese children with very low birth weight.

BACKGROUND: Developmental programming of chronic kidney disease (CKD) in young adults is linked to preterm birth and intrauterine growth restriction (IUGR). Which confers a higher risk of progression to chronic kidney damage in children with very low birth weight (VLBW; born weighing < 1500 g): prematurity or IUGR? METHODS: This is a national historical cohort study of children with VLBW cared for in perinatal medical centers in Japan. Predictive factors included three latent variables (prematurity, IUGR, stress during neonatal period) and eight observed variables (gestational age, birth weight Z-score, maternal age, duration of treatment with antibiotics and diuretics, maternal smoking, late-onset circulatory collapse, kidney dysfunction) during the perinatal period. The primary endpoint was estimated glomerular filtration rate (eGFR) at age ≥ 3 years. A structural equation model was used to examine the pathologic constitution. RESULTS: The 446 children with VLBW included 253 boys and 193 girls, of mean age 5.8 ± 2.6 years and mean eGFR 111.7 ml/min/1.73 m2 at last encounter. Pathway analyses showed intrauterine malnutrition (ß = 0.85) contributed more to chronic kidney damage than stress during the neonatal period (ß = - 0.19) and prematurity (ß = 0.12), and kidney dysfunction and late-onset circulatory collapse were important observed variables in stress during the neonatal period. CONCLUSIONS: IUGR was more harmful to future kidneys of VLBW neonates. Neonatal kidney dysfunction and late-onset circulatory collapse were important risk factors for subsequent CKD development. This emphasizes the need for obstetricians to monitor for fetal growth restriction and neonatologists to minimize neonatal stress to prevent CKD in later life.

Association of crumbs homolog-2 with mTORC1 in developing podocyte.

The evidence that gene mutations in the polarity determinant Crumbs homologs-2 (CRB2) cause congenital nephrotic syndrome suggests the functional importance of this gene product in podocyte development. Because another isoform, CRB3, was reported to repress the mechanistic/mammalian target of the rapamycin complex 1 (mTORC1) pathway, we examined the role of CRB2 function in developing podocytes in relation to mTORC1. In HEK-293 and MDCK cells constitutively expressing CRB2, we found that the protein localized to the apicolateral side of the cell plasma membrane and that this plasma membrane assembly required N-glycosylation. Confocal microscopy of the neonate mouse kidney revealed that both the tyrosine-phosphorylated form and non-phosphorylated form of CRB2 commence at the S-shaped body stage at the apicolateral side of podocyte precursor cells and move to foot processes in a capillary tuft pattern. The pattern of phosphorylated mTOR in developing podocytes was similar to that of CRB2 tyrosine phosphorylation. Additionally, the lack of a tyrosine phosphorylation site on CRB2 led to the reduced sensitivity of mTORC1 activation in response to energy starvation. CRB2 may play an important role in the mechanistic pathway of developing podocytes through tyrosine phosphorylation by associating with mTORC1 activation.

Ensuring safe drug administration to pediatric patients with renal dysfunction: a multicenter study.

BACKGROUND: In pediatric patients, due to variations in baseline serum creatinine (Cr) reference values, renal dysfunctions sometimes go unnoticed. In addition, renally excreted drugs need dose adjustment while nephrotoxic drugs should be avoided altogether in patients with impaired renal function. However, most physicians are apparently unaware of these facts and may administer these drugs to vulnerable patients. METHODS: We administered a questionnaire to all physicians and pharmacists specializing in pediatric medical care at six Tokyo metropolitan government-run hospitals in Japan. RESULTS: 276 (59%) of 470 physicians and pharmacists participated. The rate of correct answers given by physicians who were asked to state the serum Cr reference range for 4-year-olds and 8-year-olds was 83 and 74%, respectively. On the other hand, the rate of correct answers given by pharmacists to the same question was only 27 and 24%, respectively. Only about 50% of physicians were aware that histamine H2-receptor antagonists and oseltamivir are renally excreted or that acyclovir and angiotensin II receptor blocker are nephrotoxic. However, most of the pharmacists recognized that histamine H2-receptor antagonists and oseltamivir are renally excreted drugs. CONCLUSIONS: For the majority of the investigated drugs, the awareness that we need to reduce dosages for patients with renal dysfunction was insufficient. To ensure safe drug administration, communication between physicians and pharmacists is paramount. There is an urgent need for the creation of a safe drug administration protocol for pediatric patients with renal dysfunction.