Case Report: The Application of Dupilumab in Atopic Dermatitis Children Complicated With Nephrotic Syndrome.

Nephrotic syndrome (NS) tends to be more common in patients with history of allergies. Atopic dermatitis (AD) is one of the most common allergic diseases in children. Dupilumab, a dual IL-4 and IL-13 inhibitor, has been widely used to treat AD patients. However, the efficacy and safety of Dupilumab in NS is unclear. We reported two AD patients with NS comorbidities treated with Dupilumab. The outcomes showed the good control of NS and less systemic steroids and/or immunosuppressive agents use during the Dupilumab treatment period, accompanied by significant relief of AD symptoms. We suggest prospective pilot studies and randomized controlled trials could be carried out to validate the efficacy and safety of Dupilumab in the treatment of NS patients.

Possible PKHD1 Hot-spot Mutations Related to Early Kidney Function Failure or Hepatofibrosis in Chinese Children with ARPKD: A Retrospective Single Center Cohort Study and Literature Review.

PKHD1 mutations are generally considered to cause autosomal recessive polycystic kidney disease (ARPKD). ARPKD is a rare disorder and one of the most severe conditions leading to end-stage renal disease in childhood. With the biallelic deletion mutation, patients have difficulty in surviving the perinatal period, resulting in perinatal or neonatal death. This study retrospectively analyzed patient characteristics, imaging characteristics, laboratory examinations and family surveys from 7 Chinese children with different PKHD1 gene mutations diagnosed by high-throughput sequencing from January 2014 to February 2018. Of the 7 children, there were 3 males and 4 females. Eight missense mutations, two frameshift mutations, two deletion mutations, and two intronic slicing mutations were identified. Six of the mutations have not previously been identified. In the literature search, we identified a total of 29 Chinese children with PKHD1 mutations. The missense mutation c.2507T>C in exon 24 was found in one patient in our study, and five patients with liver fibrosis but normal renal function were reported in the literature. The missense mutation c.5935G>A in exon 37 was found in two patients in our study and three cases in the literature. Four patients had renal failure at an age as young as 1 year of those five patients with the missense mutation c.5935G>A in exon 37. It was concluded that: (1) Kidney length more than 2-3 SDs above the mean and early-onset hypertension might be associated with PKHD1-associated ARPKD; (2) The more enlarged the kidney size is, the lower the renal function is likely to be; (3) c.5935G>A may be a hot spot that leads to early renal failure in Chinese children with PKHD1 mutations; (4) c.2507T>C may be a hot-spot mutation associated with hepatic lesions in Chinese children with PKHD1.

Relationship between Vesicoureteral Reflux and Glomerular Filtration Rate in Children.

Vesicoureteral reflux (VUR) is one of the most common urinary tract anomalies in children and causes renal damage and studies focusing on the effect of VUR on renal function are rare. We recruited 35 primary VUR patients with recurrent urinary tract infection (UTI) and 10 non-VUR patients with recurrent UTI. Contrast-enhanced voiding urosonography (ceVUS) was performed for VUR grading, and renal dynamic imaging was used for evaluating glomerular filtration rate (GFR, mL/min). Standardized GFR (sGFR), namely GFR/BSA (mL·min-1·m-2), was calculated based on the body surface area (BSA). Total sGFR (tsGFR, mL·min-1·m-2) was obtained from the sum of sGFR on the left and right sides of all the children. The risk of renal regurgitation was equal in the unilateral reflux group. The sGFR of children with grade IV (45.74±18.05 mL·min-1·m-2) and grade V (49.67±23.63 mL·min-1·m-2) reflux was significantly lower than that in children with grade III (77.69 ±22.21 mL·min-1·m-2). The renal function compensation of contralateral non-reflux kidney increased in unilateral reflux group, which was higher than that in the control group and level II, IV and V of reflux group respectively. In VUR group of the same grade, sGFR decreased with the age at diagnosis. In unilateral grade V reflux group, the tsGFR was lower than that in the unilateral grade III reflux group (133.51±48.21 vs. 186.87±53.49 mL·min-1·m-2). The patients with VUR of unilateral grade II were significantly older than those with VUR of unilateral grades III and IV. This study indicates that severe VUR is significantly associated with decreased renal function. Therefore, VUR should be diagnosed early and managed individually.

Kindergartens Reopening in the Period of Regular Epidemic Prevention and Control, Benefitial or Harmful?

In the period of regular epidemic prevention and control of Coronavirus disease 2019 (COVID-19) in our country, work resumption has been fully advanced. But there are still new sporadic local cases and imported cases across the country. In this situation, whether kindergartens reopening will increase the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread still remains uncertain. We reviewed two pediatric patients with moderate COVID-19, collected the epidemiologic information and monitored the cycle threshold value of rectal specimen and the viral loads, and discussed the transmission of SARS-CoV-2 in pediatric patients and the virulence of feces in children with moderate COVID-19, in order to analyze the risk of kindergartens reopening.

Risk factors and prognostic factors of acute kidney injury in children: A retrospective study between 2003 and 2013.

Recent report on epidemiology of acute kidney injury (AKI) is lacking for Chinese children. We aimed to investigate the risk factors for stage and prognostic factors for renal recovery in hospitalized children. Pediatric patients (≤18 years old) admitted during 2003 to 2013 were enrolled in this study. AKI was defined and staged using Kidney Disease Improving Global Outcomes (KDIGO) criteria. Logistic regression analysis was performed to determine the risk factors and prognostic factors. The morbidity of pediatric AKI was 0.31% (205/65 237). There were 45 (22.0%) cases in stage III, 30 (14.6%) cases in stage II and 130 (63.4%) cases in stage III. The majority of etiologies were intrinsic renal defects (85.4%). Age, weight, vomit, etiology, blood urea nitrogen (BUN) at admission and several blood gas measurements were associated with AKI stage III. Age (OR=0.894; 95% CI, 0.832-0.962; P=0.003), vomit (OR=2.375; 95% CI, 1.058-5.333; P=0.036) and BUN at admission (OR=1.135; 95% CI, 1.085-1.187; P<0.001) were identified as independent risk factors for AKI stage III. After treatment, 172 (83.9%) patients achieved complete or partial recovery. The mortality was 3.9%. Variables were found as prognostic factors for renal recovery, such as age, stage, hospital stay, BUN at discharge, white blood cells, red blood cells, platelets (PLTs), blood pH and urine blood. Among them, AKI stage (stage III vs. stage I; OR, 6.506; 95% CI, 1.640-25.816; P=0.008), BUN at discharge (OR, 0.918; 95% CI, 0.856-0.984; P=0.016) and PLTs (OR, 1.007; 95% CI, 1.001-1.013; P=0.027) were identified as independent prognostic factors. AKI is still common in Chinese hospitalized children. Identified risk factors and prognostic factors provide guiding information for clinical management of AKI.

Twenty-three-year review of disease patterns from renal biopsies: an experience from a pediatric renal center.

BACKGROUND: The aim of this study was to investigate the clinical and pathological characteristics as well as their associations with trends for diseases in 1,579 pediatric renal biopsies from 1989 to 2012. METHODS: The clinical and pathological data were retrospectively analyzed for children undergoing renal biopsy from 1989 to 2012 in our hospital. RESULTS: Primary glomerulonephritis (PGN) accounted for 60.1% of total cases, followed by secondary glomerulonephritis (SGN) (31.2%) and hereditary nephropathy (8.3%). The major clinical patterns of PGN and SGN were nephritic syndrome (NS) and Henoch-Schönlein purpura nephritis (HSPN), respectively. Minimal change disease/mild disease (MCD/ML), IgAN and mesangial proliferative glomerulonephritis (MsPGN) were the most common pathological patterns of PGN. Male patients were most likely to suffer from NS, HBV-associated glomerulonephritis (HBVGN) or Alport syndrome, while females were most likely to suffer from isolated hematuria, rapidly progressive glomerulonephritis (RPGN), lupus nephritis (LN), ANCA-associated glomerulonephritis or thin basement membrane disease. The proportions of NS, isolated hematuria, acute nephritic syndrome, chronic nephritic syndrome, HBVGN, LN and hemolytic uremic syndrome changed significantly with aging. The clinical patterns of PGN were significantly correlated with the distribution of pathological types: MCD/ML and IgMN presented most often as NS; MCD/ML and IgAN presented most often as isolated hematuria; IgAN and MsPGN presented most often as hematuria with proteinuria. The spectrum of NS, HSPN, HBVGN and IgAN changed during the 23 years, and the percentage of repeated renal biopsies was low (1.2%) in pediatric cases with kidney disease. CONCLUSIONS: Glomerular diseases in children are closely related to age and sex of patient. The spectrum of kidney diseases from our center has changed significantly over the last 23 years.

[Clinical and pathological characterization of antineutrophil cytoplasmic antibody associated small vasculitis in children].

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA) associated small vasculitides (ASV) are rare in children and often complicated in clinical manifestations and have very poor prognosis. In order to deepen our understanding of ANCA-associated small vasculitis (ASV) in children, the present study aimed to characterize their clinical manifestations, serum ANCA and renal histopathological findings and outcomes in Chinese children. METHODS: Serum ANCA was qualitatively tested with indirect immunofluorescence microscopy and anti-proteinase 3 (PR(3)) and anti-myeloperoxidase (MPO) activity were quantitated by enzyme-linked immunosorbent assays (ELISA), and renal biopsies were done to investigate the pathological changes. The clinical manifestation, serum ANCA and renal histopathological findings and outcome were characterized in 5 children with ANCA associated small vasculitis. RESULTS: (1) Five children with ANCA associated small vasculitis only accounted for 1.20% of children in whom renal biopsy was performed and 0.25% of hospitalized children with renal diseases during the same period. The age of onset of the 5 children with ASV was between 8 to 12 years with mean age 10.5 years. All ASV children were female. (2) All ASV children were negative for C-ANCA and showed normal anti-proteinase 3 activities, but positive for P-ANCA with high anti-myeloperoxidase activities between 98 to 242 kEU/L. The mean value of MPO-ANCA was 154.5 kEU/L (normal range < 12.7 kEU/L). (3) All ASV in the children was microscopic polyarteritis with wide-spread glomerular crescents formation and capillary tuft fibrinoid necrosis. Variety of complement C3 deposits and weak immunoglobulin deposits were noted in all ASV but one child who showed relatively strong deposits of IgA and IgM. The electronic dense deposits were mainly located in subendothelial space but were also found in the glomerular basement membrane in one child. (4) Three children with ASV died within one year after diagnosis, and two got remission and restored renal function after combined pulse therapy with methylprednisolone and cyclophosphamide (CTX), but remained to have hematuria and small amount of proteinuria after 1 and 5 year follow-up, respectively. CONCLUSION: Childhood ASV was female and P-ANCA predominant, more vulnerable to progress to renal failure and poorer in prognosis than adult cases. Qualitative and quantitative ANCA measurement and renal biopsy were key to the diagnosis of ASV in children.