Background and Objectives:
Maturation of the gut microbiota (GM) in infants is critically affected by environmental factors, with potential long-lasting clinical consequences. Continuous low-dose ...antibiotic prophylaxis (CAP) is the standard of care for children with vesicoureteral reflux (VUR), in order to prevent recurrent urinary tract infections. We aimed to assess short-term GM modifications induced by CAP in infants.
Methods:
We analyzed the GM structure in 87 infants (aged 1-5 months) with high-grade VUR, previously exposed or naïve to CAP. Microbial DNA was extracted from stool samples. GM profiling was achieved by 16S rRNA gene-based next-generation sequencing. Fecal levels of short- and branched-chain fatty acids were also assessed.
Results:
36/87 patients had been taking daily CAP for a median time of 47 days, while 51/87 had not. In all patients, the GM was predominantly composed by
Bifidobacteriaceae
and
Enterobacteriaceae
. Subgroup comparative analysis revealed alterations in the GM composition of CAP-exposed infants at phylum, family and genus level. CAP-exposed GM was enriched in members of
Enterobacteriaceae
and Bacteroidetes, especially in the genera
Bacteroides
and
Parabacteroides
, and showed a trend toward increased
Klebsiella
, often associated with antibiotic resistance. In contrast, the GM of non-CAP children was mostly enriched in
Bifidobacterium
. No differences were found in fatty acid levels.
Conclusions:
In infants with VUR, even a short exposure to CAP definitely alters the GM composition, with increased relative abundance of opportunistic pathogens and decreased proportions of health-promoting taxa. Early low-dose antibiotic exposure might bear potential long-term clinical risks.
Steroid-sensitive nephrotic syndrome is an immunological disorder mediated by still poorly defined circulating factor(s) that target the podocyte and damage the filtration barrier. Fatty acids (FA) ...have several biological roles and, in particular, are strictly involved in cell to cell communication, inflammatory processes and regulation of lymphocyte pools. Studies of FAs during INS have been mainly focused on biochemical changes during the phase of proteinuria; while no information is available about FA profile in patients with idiopathic nephrotic syndrome (INS) on stable remission. Aim of this study is to assess differences in blood FA profile between pediatric patients with INS during the phase of stable remission. Blood fatty acid profile of 47 pediatric patients on stable remission and 47 matched healthy controls were evaluated with gas chromatography. Patients with INS on stable remission had significantly higher levels of PUFA and omega-6 than controls (40.17 vs. 37.91% and 36.95 vs. 34.79%), lower levels of SFA and MUFA. Considering the single fatty acids, levels of omega-6 18:2n6 linoleic acid and omega-6 20:4n6 arachidonic acid were significantly higher in patients with INS than in controls (23.01 vs. 21.55%,
-value 0.003 and 10.37 vs. 9.65%,
-value 0.01). Moreover, patients with INS showed lower levels of SFA 14:0 (0.74 vs. 0.92%) and 18:0 (10.74 vs. 11.74%) and MUFA 18:1n9 oleic acid (18.50 vs. 19.83%). To the best of our knowledge this is the first study assessing FAs profile in children with INS in stable remission. In a population of 47 patients, we were able to demonstrate a higher blood level of linoleic and arachidonic acid, and consequently of omega-6 and PUFA, compared to controls. Persistently higher than normal levels of either linoleic or arachidonic acid, could be viewed as candidate biomarker for a state of risk of relapse in children with idiopathic nephrotic syndrome.
Background:
A great majority of children with idiopathic nephrotic syndrome will relapse after successful treatment of the initial episode. The possibility that different steroid dosing regimens at ...onset, adjusted for risk factors, can reduce the rate of relapse represents an interesting option to investigate.
Objectives:
To evaluate the effect of the initial steroid regimen, adjusted for time to remission (TTR), on the frequency of relapses and steroid dependence, and to verify the influence of prognostic factors on disease course.
Methods:
A multicentre, prospective, cohort study. Children with nephrotic syndrome, with TTR ≤ 10 days (Group A), were given a 20-week prednisone regimen (2,828 mg/m
2
) and those with a TTR >10 days, a 22-week regimen (3,668 mg/m
2
) (Group B). Previously published retrospective data from the same centers were also evaluated. Main outcomes were: relapse rate, number of frequent relapsers + steroid dependent children and total prednisone dose after induction.
Results:
143 children were enrolled. Rate of relapsed subjects (77 vs. 79%) and frequent relapsers + steroid dependent subjects (40 vs. 53%) did not differ between Groups A and B, or between the retrospective and prospective cohorts. The cumulative prednisone dose taken after the induction treatment was similar in both groups and in the retrospective and prospective cohorts. TTR was not associated with relapse risk. Age at onset and total serum protein were significantly lower in relapsing patients. At ROC analysis, the best cut-off was 5.3 years for age at onset and 4.2 g/dL for total serum protein. According to these cut-offs, older children with higher total serum protein had a higher relapse free survival rate (58%) than younger children with lower total serum protein (17%).
Conclusions:
TTR was not found to be a prognostic factor of relapse; because of this, different steroid regimens, adjusted for TTR, did not modify the relapse rate in any relevant measure. Conversely, younger age and low total serum protein were independent predictors of relapse risk, however this outcome was not modified by higher prednisone regimens.
Clinical Trial Registration:
https://www.ClinicalTrials.gov/
, identifier: NCT01386957 (
www.nefrokid.it
).
Background
Children with underlying kidney diseases display a mild course of SARS-CoV-2 infection, but they only accounted for a minority of cases until the spread of the Omicron variant. ...Nonetheless, idiopathic nephrotic syndrome (INS) has been advocated as a predictor of worse outcome.
Methods
We investigated the spread, severity, and risk of relapse related to SARS-CoV-2 infection among children with INS. The incidence and characteristics of SARS-CoV-2 infections, immunosuppression, and vaccination status were retrospectively collected from the beginning of the pandemic to May 31, 2022.
Results
We enrolled 176 patients (73 females, median age 10.22 years); 28 had a steroid-resistant disease, and 108 (61.4%) were on immunosuppressive therapy. Sixty-one (34.7%) patients reported a SARS-CoV-2 infection, with incidence peaking between December 2021 and January 2022. No hospitalization or deaths were reported, and symptoms were absent or mild. The rate of SARS-CoV-2 infection was similar in children with and without immunosuppression (33.8% vs 35.2%;
p
= 0.85). None of the 38 immunosuppressed patients discontinued the therapy, but they had a longer time to negativization (13.31 vs. 10.04 days;
p
= 0.03). Proteinuria was detected in 7 patients, but only one had a relapse requiring steroid therapy, with prompt remission and a mild course.
Conclusions
After the spread of the Omicron variant, the rate of SARS-CoV-2 infection in children with INS was much higher than previously reported. In this large cohort, symptoms were mild, even in immunosuppressed patients and those with proteinuria. During the infection, transient proteinuria was common with a low rate of relapses.
Graphical abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information
Single nucleotide polymorphisms (SNPs) in gene encoding pro- and anti-inflammatory factors have been associated with the occurrence of aGvHD. We retrospectively tested a wide panel of 38 ...polymorphisms in 19 immunoregulatory genes, aiming to first establish, in a pediatric HSCT setting, which SNPs were significantly associated with the development of aGvHD. A significant association was found between aGvHD grades II–IV and SNPs of donor IL10-1082GG, and Fas-670CC + CT and recipient IL18-607 TT + TG genotype. aGvHD grades III-IV resulted associated with donor IL10-1082GG, Fas-670CC + CT, and TLR4-3612TT as well as the use of peripheral CD34+ cells as stem cell source. The multivariate analysis confirmed the association between donor IL10-1082GG and Fas-670CC + CT and aGvHD grades II–IV and between donor IL10-1082GG and TLR4-3612TT and aGvHD grades III-IV. In conclusion we found an association between IL10, FAS, and TLR4 in the donor and IL18 in the recipient and an increased risk of developing aGvHD in transplanted children. Knowledge of the SNPs of cytokine genes associated with aGvHD represents a useful tool for an integrated pretransplantation risk assessment and could guide the physicians to an optimal and more accurate HSCT planning.
Acute pyelonephritis in children Morello, William; La Scola, Claudio; Alberici, Irene ...
Pediatric nephrology (Berlin, West),
08/2016, Letnik:
31, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Acute pyelonephritis is one of the most serious bacterial illnesses during childhood.
Escherichia coli
is responsible in most cases, however other organisms including
Klebsiella, Enterococcus, ...Enterobacter, Proteus
, and
Pseudomonas
species are being more frequently isolated. In infants, who are at major risk of complications such as sepsis and meningitis, symptoms are ambiguous and fever is not always useful in identifying those at high risk. A diagnosis of acute pyelonephritis is initially made on the basis of urinalysis; dipstick tests for nitrites and/or leukocyte esterase are the most accurate indicators of infection. Collecting a viable urine sample for urine culture using clean voided methods is feasible, even in young children. No gold standard antibiotic treatment exists. In children appearing well, oral therapy and outpatient care is possible. New guidelines suggest less aggressive imaging strategies after a first infection, reducing radiation exposure and costs. The efficacy of antibiotic prophylaxis in preventing recurrence is still a matter of debate and the risk of antibiotic resistance is a warning against its widespread use. Well-performed randomized controlled trials are required in order to better define both the imaging strategies and medical options aimed at preserving long-term renal function.
Acute pyelonephritis may result in renal scarring. Recent prospective studies have shown a small benefit of antibiotic prophylaxis in preventing symptomatic and febrile urinary tract infections ...(UTIs), while being underpowered to detect any influence in prevention of renal damage.
Review of the literature and a meta-analysis to evaluate the effect of antibiotic prophylaxis on UTI-related renal scarring.
Medline, Embase, and Cochrane Controlled Trials Register electronic databases were searched for studies published in any language and bibliographies of identified prospective randomized controlled trials (RCTs) performed and published between 1946 and August 2016.
Subjects 18 years of age or younger with symptomatic or febrile UTIs, enrolled in prospective RCTs of antibiotic prophylaxis where
Tc dimercaptosuccinic acid scans were performed at entry into the study and at late follow-up to detect new scar formation.
The literature search, study characteristics, inclusion and exclusion criteria, and risk of bias assessment were independently evaluated by 2 authors.
Seven RCTs (1427 subjects) were included in the meta-analysis. Our results show no influence of antibiotic prophylaxis in preventing renal scarring (pooled risk ratio, 0.83; 95% confidence interval, 0.55-1.26) as did a subanalysis restricted to those subjects with vesicoureteral reflux (pooled risk ratio, 0.79; 95% confidence interval, 0.51-1.24).
Limitations include the small number of studies, short duration of follow-up, and insufficient children with high-grade dilating reflux and/or renal dysplasia enrolled in the studies.
Antibiotic prophylaxis is not indicated for the prevention of renal scarring after a first or second symptomatic or febrile UTI in otherwise healthy children.
Background
Histological findings of kidney involvement have been rarely reported in pediatric patients with SARS-CoV-2 infection. Here, we describe clinical, laboratory, and histological findings of ...two pediatric cases with almost exclusive kidney involvement by SARS-CoV-2.
Results
A 10-year-old girl with IgA vasculitis nephritis underwent kidney biopsy, showing diffuse and segmental mesangial-proliferative glomerulonephritis, and steroid therapy was initiated. After the worsening of the clinical picture, including an atypical skin rash, she was diagnosed with SARS-CoV-2. The re-evaluation of initial biopsy showed cytoplasmatic blebs and virus-like particles in tubular cells at electron microscopy. Despite SARS-CoV-2 clearance and the intensification of immunosuppression, no improvement was observed. A second kidney biopsy showed a crescentic glomerulonephritis with sclerosis, while virus-like particles were no longer evident.
The second patient was a 12-year-old girl with a 3-week history of weakness and weight loss. Rhinitis was reported the month before. No medications were being taken. Blood and urine analysis revealed elevated serum creatinine, hypouricemia, low molecular weight proteinuria, and glycosuria. A high SARS-CoV-2-IgG titre was detected. Kidney biopsy showed acute tubular-interstitial nephritis. Steroid therapy was started with a complete resolution of kidney involvement.
Conclusion
We can speculate that in both cases SARS-CoV-2 played a major role as inflammatory trigger of the kidney damage. Therefore, we suggest investigating the potential kidney damage by SARS-CoV-2 in children. Moreover, SARS-CoV-2 can be included among infectious agents responsible for pediatric acute tubular interstitial nephritis.
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