Utility of the Global Respiratory Severity Score for predicting the need for respiratory support in infants with respiratory syncytial virus infection.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of acute respiratory infection in children. One of the most important strategies for treatment of an RSV infection is to decide whether the patient needs respiratory support. This study aimed to assess the validity and clinical benefit of the Global Respiratory Severity Score (GRSS) and the Wang bronchiolitis severity score (WBSS) for clinical decision-making regarding providing respiratory support (high-flow nasal cannula, nasal continuous positive airway pressure, or ventilator) in infants with an RSV infection. STUDY DESIGN AND METHODS: This retrospective cohort study enrolled 250 infants aged under 10 months who were admitted to Atsugi City Hospital with an RSV infection between January 2012 and December 2019. The utility of these scores was evaluated for assessing the need for respiratory support through decision curve analysis by calculating the optimal GRSS and WBSS cut-offs for predicting the need for respiratory support. RESULTS: Twenty-six infants (10.4%) received respiratory support. The optimal cut-offs for the GRSS and the WBSS were 4.52 and 7, respectively. Decision curve analysis suggested that the GRSS was a better predictive tool than the WBSS if the probability of needing respiratory support was 10-40%. CONCLUSIONS: The GRSS was clinically useful in determining the need for respiratory support in infants aged under 10 months with an RSV infection.

Reference serum creatinine levels according to sex, age, and height in children with Down syndrome.

Standard serum creatinine (S-Cr) levels in healthy children fluctuate with age and sex. However, it is unclear if this fluctuation in S-Cr levels is present for children with Down syndrome (DS) who show atypical growth rate. Therefore, we aimed to establish specific reference S-Cr levels for DS and compare them with the prevailing standard levels. We retrospectively reviewed 984 children with DS aged 3 months to 18 years who visited our medical center. Patients with diseases affecting S-Cr levels were excluded. We calculated the reference S-Cr levels according to sex, age, and length/height using medical records. A total of 3765 examinations of 568 children with DS were registered for this study. Ages and S-Cr levels were examined for boys (y = 0.032x + 0.20; r = 0.868, P < 0.0001), and girls (y = 0.024x + 0.23; r = 0.835, P < 0.0001). S-Cr levels in children aged >9 years were significantly higher in boys than in girls. The 430 children with DS aged 2-8 years were examined 1867 times. Height and S-Cr levels showed a significantly strong positive correlation (r = 0.670, P < 0.001) with regression equation y = 0.37x. The quintic equations calculated with S-Cr levels and length/height for boys (336 children, 2043 tests, r = 0.887) and girls (232 children, 1722 tests, r = 0.805) werey = - 6.132x5 + 32.78x4 - 67.86x3 + 68.31x2 - 33.14x + 6.41, and y = 0.09542x5 + 1.295x4 - 6.401x3 + 10.35x2 - 6.746x + 1.772. All calculated results varied from the standard levels for healthy children.Conclusion: This study established reference S-Cr levels and quintic equations specific for children with DS. These reference levels would be potentially useful in evaluating S-Cr levels and renal function in this population. What is Known: •Standard serum creatinine levels vary with age and sex to reflect muscle mass. •Reference serum creatinine levels specific to children with Down syndrome who show growth rates different from those of healthy children have not been established. What is New: •Serum creatinine levels in children with Down syndrome showed different trajectories for sex, age, and length/height when compared with the standard levels for healthy children. •This report on specific reference serum creatinine levels for children with Down syndrome is useful in the assessment of renal function in these children.

Body temperature predicts recurrent febrile seizures in the same febrile illness.

BACKGROUND: The incidence of recurrent febrile seizures during the same febrile illness (RFS) is 14-24%. A pilot study found that body temperature and male sex were predictors of RFS. This study sought to validate body temperature as a predictor of RFS, calculate the optimal cut-off body temperature for predicting RFS, and identify the other predictors of RFS. METHODS: This prospective cohort study enrolled children with febrile seizures aged 6-60 months who visited the emergency department at Atsugi City Hospital, Japan, between March 1, 2019, and February 29, 2020. Children who had multiple seizures, diazepam administration before the emergency department visit, seizures lasting >15 min, underlying diseases, or who could not be followed up were excluded. The optimal cut-off body temperature was determined using a receiver-operating characteristic curve. RESULTS: A total of 109 children were enrolled, of whom 13 (11.9%) had RFS. A lower body temperature was significantly associated with RFS (P = 0.02). The optimal cut-off body temperature for predicting RFS was 39.2 °C. Children with RFS also had significantly lower C-reactive protein and blood glucose levels (P = 0.01 and 0.047, respectively), but none of the other factors considered were significantly associated with RFS. CONCLUSIONS: This large prospective study confirmed that body temperature is a predictor of RFS. The optimal cut-off body temperature for predicting RFS was 39.2 °C. Low C-reactive protein level and blood glucose level might be predictors of RFS, but this needs to be confirmed in prospective multicenter studies.

Familial juvenile hyperuricemia in early childhood in a boy with a novel gene mutation.

Familial juvenile hyperuricemic nephropathy (FJHN) is a rare autosomal dominant disease caused by mutations in the uromodulin (UMOD) gene. It is characterized by the development of gout, tubulointerstitial nephropathy, and end-stage renal disease. Here we report a case of FJHN that was diagnosed in early childhood in a boy with a novel gene mutation. At the age of 4 years, the patient was admitted with a diagnosis of purpura nephritis. He was discharged following symptom alleviation. However, hyperuricemia (7-9 mg/dL) and mild renal dysfunction [creatinine-estimated glomerular filtration rate (eGFR): 80-90 mL/min/1.73 m2] persisted after discharge. FJHN was suspected on the basis of a maternal family history of hyperuricemia, renal dysfunction, and dialysis. Direct sequence analysis performed at the age of 5 years revealed a novel missense mutation (c766T > G), p.Cys256Gly, in exon 3. Urate-lowering therapy was started, which provided good uric acid control (6.0 mg/dL). At the age of 8 years, persistent renal dysfunction was observed (eGFR: 80-90 mL/min/1.73 m2). Interestingly, cases of FJHN with c744C > G (p.Cys248Trp) mutations also exhibit a high incidence of juvenile onset, and identical disulfide bridges are considered responsible for the accumulation of mutant UMOD in the endoplasmic reticulum. Pediatricians should consider UMOD mutation analysis for families with autosomal dominant tubulointerstitial kidney disease (ADTKD) and a bland urinary sediment, even if hyperuricemia is mild. Also, sex and genotype are very important prognostic factors for ADTKD caused by UMOD mutations.

Impact of acute kidney injury in patients prescribed angiotensin-converting enzyme inhibitors over the first two years of life.

BACKGROUND: The association of long-term acute kidney injury (AKI) risk with angiotensin-converting enzyme (ACE) inhibitor use in neonates/infants is poorly understood. We examined this association to identify potential AKI risk factors. METHODS: We retrospectively evaluated 119 children aged < 2 years (72 boys; median age, 5.0 months) who received ACE inhibitors for congenital heart disease for ≥ 6 months between January 2009 and June 2019. We monitored the occurrence of AKI, defined according to the Kidney Disease Improving Global Outcomes guidelines. Demographic and clinical data were extracted from medical records. Risk factors associated with AKI onset were identified by a Cox proportional hazards regression analysis of variables previously identified as risk factors of AKI and those significant in a univariate analysis. RESULTS: Thirty-three of 119 patients (28%) developed AKI at a median follow-up of 1.3 years (interquartile range, 0.8-3.2 years). AKI incidence was 1257 events per 10,000 patient-years. Concomitant tolvaptan use (hazard ratio [HR], 3.81; 95% confidence interval [CI], 1.82-7.97; P < 0.01) and Down syndrome (HR, 3.22; 95% CI, 1.43-7.29; P < 0.01) were identified as independent risk factors of AKI onset. CONCLUSIONS: AKI was strongly associated with concomitant tolvaptan use and Down syndrome in our study population. Physicians should consider these factors when prescribing ACE inhibitors for neonates/infants. Low-dose ACE inhibitors slow CKD progression because of their antifibrotic properties. ACE inhibitors may be beneficial for patients with Down syndrome who have underlying CKD in a non-acute setting. Therefore, they should be administered to such patients with caution.

Is the estimated glomerular filtration rate formula useful for evaluating the renal function of Down syndrome?

BACKGROUND: Children with Down syndrome (DS) have different growth rates compared with normal children. The present study examined the reliability of a general formula, Uemura's formula, utilized in normal Japanese children to estimate renal function (estimated glomerular filtration rate - eGFR) in children with DS. METHODS: This study included 758 children aged 2-18 years with DS who visited our medical center. Patients with congenital heart disease, or congenital anomalies of the kidney or urinary tract detected via abdominal ultrasonography, chronic glomerulonephritis, and vesicoureteral reflux, etc., were excluded. Height and serum creatinine data gathered from 2421 examinations of 379 children with DS (224 boys and 155 girls) were used to evaluate Uemura's formula. RESULTS: The mean eGFR was lower in children with DS than in children without DS. Stage II chronic kidney disease was indicated in 44.6% of examinations and stage III in 0.8%. The association of eGFR with age differed between sexes. Boys with DS showed a significant but weak negative correlation between eGFR and age (r = -0.273, P < 0.001), whereas girls with DS showed a significant but very weak negative correlation (r = -0.111, P < 0.001). CONCLUSIONS: A new eGFR formula that takes into account specific growth rates and puberty is needed for children with DS because general renal function evaluation formulas are inappropriate for these patients.

Independent risk factors and long-term outcomes for acute kidney injury in pediatric patients undergoing hematopoietic stem cell transplantation: a retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) remains a frequent complication in children undergoing hematopoietic stem cell transplantation (HSCT) and an independent risk factor of the patient's survival and a prognostic factor of progression to chronic kidney disease (CKD). However, the causes of these complications are diverse, usually overlapping, and less well understood. METHODS: This retrospective analysis was performed in 43 patients (28 boys, 15 girls; median age, 5.5 years) undergoing HSCT between April 2006 and March 2019. The main outcome was the development of AKI defined according to the Pediatric Risk, Injury, Failure, Loss, End-stage Renal Disease (pRIFLE) criteria as ≥ 25% decrease in estimated creatinine clearance. The secondary outcome was the development of CKD after a 2-year follow-up. RESULTS: AKI developed in 21 patients (49%) within 100 days after HSCT. After adjusting for possible confounders, posttransplant AKI was associated with matched unrelated donor (MUD) (HR, 6.26; P = 0.042), but not total body irradiation (TBI). Of 37 patients who were able to follow-up for 2 years, 7 patients died, but none had reached CKD during the 2 years after transplantation. CONCLUSIONS: Posttransplant AKI was strongly associated with HSCT from MUD. Although the incidence of AKI was high in our cohort, that of posttransplant CKD was lower than reported previously in adults. TBI dose reduced, GVHD minimized, and infection prevented are required to avoid late renal dysfunction after HSCT in children since their combinations may contribute to the occurrence of AKI.

Predictors of recurrent febrile seizures during the same febrile illness in children with febrile seizures.

Febrile seizures (FS) are common in childhood. Of children who experience an FS, 14-24% experience recurrence within 24 h, during the same febrile illness (RFS). The aim of this pilot study was to identify the predictors of RFS among children who experience FS. We conducted a retrospective cohort study of children aged 6-60 months, who visited the emergency department (ED) at Atsugi City Hospital in Japan for treatment of an FS between December 1, 2018 and February 28, 2019. Exclusion criteria included multiple seizures before visiting the ED, diazepam administration before visiting the ED or on departure, seizures lasting >15 min, underlying diseases such as epilepsy, and absence of laboratory test results. The primary outcome was RFS. Fifty-one patients fulfilled the inclusion criteria, of whom nine (17.6%) had RFS. The incidence of RFS was significantly higher in children with a body temperature ≤ 39.8 °C during the ED visit (P = .01). The combination of male sex and a body temperature ≤ 39.8 °C had a sensitivity, specificity and negative predictive value of 88.9%, 76.2%, and 97.0%, respectively. In conclusion, the incidence of RFS was 17.6%. The major predictors of RFS were male sex and a body temperature ≤ 39.8 °C.

Glyceraldehyde-3-phosphate dehydrogenase of Mycoplasma pneumoniae induces infection-related glomerulonephritis
.

Infection-related glomerulonephritis (IRGN) was previously thought to be due mostly to Streptococcus species, but is now known to be caused by a variety of other pathogens. Nephritis-associated plasmin receptor (NAPlr) was originally isolated from group A streptococci as the protein responsible for acute poststreptococcal glomerulonephritis, and was shown to be identical to streptococcal glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Here, we describe a 7-year-old boy diagnosed with Mycoplasma pneumoniae IRGN presenting with acute nephritic syndrome. Laboratory data revealed a significant increase in serum anti-M. pneumoniae antibody titer. Renal biopsy revealed diffuse global endocapillary proliferation and cellular crescents in 5/43 glomeruli examined. Although antistreptolysin O antibody titer and serum complement C3 level were within the respective normal ranges, glomeruli showed positive staining for NAPlr and upregulation of plasmin activity. In addition, positive staining for NAPlr in the glomeruli was abolished by preabsorption of anti-NAPlr antibody with recombinant M. pneumoniae GAPDH. Western blotting analysis revealed anti-NAPlr antibody reactivity with a band at around the predicted size of GAPDH in the protein isolate of M. pneumoniae (37 kDa). Furthermore, immobilized M. pneumoniae GAPDH bound to anti-NAPlr antibody as well as plasmin in vitro. These data suggest that M. pneumoniae GAPDH has a function similar to streptococcal GAPDH (NAPlr) and may induce plasmin-related glomerular damage in M. pneumoniae IRGN. NAPlr could be a marker of glomerulonephritis related to infection not only by streptococci but also by &M. pneumoniae.

Independent Risk Factors and 2-Year Outcomes of Acute Kidney Injury after Surgery for Congenital Heart Disease.

BACKGROUND: Data are limited regarding risk factors for acute kidney injury (AKI) following cardiac surgery in children with congenital heart disease (CHD). This observational study was performed to examine temporal trends in AKI incidence according to the Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease (pRIFLE) criteria, identify independent risk factors for AKI after cardiac surgery, and examine associations between AKI and long-term mortality. METHODS: We retrospectively evaluated 418 patients (259 males, 159 females; median age, 5 months) who underwent cardiac surgery for CHD between April 2007 and August 2013. Patients were followed up for 2 years. AKI was defined according to the pRIFLE criteria as ≥25% decrease in estimated creatinine clearance. RESULTS: AKI developed postoperatively in 104 cases (24.9%). Approximately 80% belonged to the "Risk" category according to the pRIFLE criteria, and only 21 cases (5%) required renal replacement therapy (peritoneal dialysis in all cases). Multivariate analysis revealed 3 independent risk factors for onset of AKI: young age (<1 year), surgery in Risk Adjustment in Congenital Heart Surgery (RACHS-1) category ≥4, and long cardiopulmonary bypass (CPB) time (≥90 min). Twenty-three patients (22%) with AKI died during the 2-year follow-up. In multivariate cox hazard regression analysis, the most significant contributor to risk of mortality was AKI. CONCLUSIONS: Postoperative AKI was strongly associated with young age, high RACHS-1 category, and prolonged CPB time. In addition, mortality rate was higher in patients who survived after recovery from AKI than in those without AKI, even among the lower pRIFLE categories.

Tolvaptan in a pediatric patient with diuretic-resistant heart and kidney failure.

Despite conventional diuretic therapy, volume overload persists in many patients with decompensated heart failure. Adverse effects of diuretics are common, including worsening kidney function and electrolyte disturbance. Furthermore, decreased kidney function also affects the response to diuretics and is associated with an increased risk of mortality. A 10-year-old boy with congestive heart failure (CHF) complicated by advanced chronic kidney disease (CKD) presented with oliguria and generalized edema. He was being treated with furosemide and spironolactone, and these doses were increased to 3 mg/kg/day after admission. Although edema decreased temporarily, the symptoms worsened and furosemide resistance developed 2 months later. Tolvaptan (0.1 mg/kg/day) was started, resulting in a gradual increase in the plasma sodium level and adequate decongestion of the volume overload state. Cardiac function also improved. The use of tolvaptan should be considered in pediatric cases of conventional diuretic-resistant CHF, even when complicated by advanced CKD.