Pediatric Nephrology最新文献

Background: Haemolytic uremic syndrome (HUS) is a life-threatening disease with a historically poor prognosis in children receiving maintenance kidney replacement therapy (KRT). This study aimed to analyse the incidence and outcome of chronic kidney disease stage 5 (CKD5) due to Escherichia coli-HUS (STEC-HUS) and complement-mediated HUS (CM-HUS) in children, compared with controls with non-HUS CKD5 over the last 24 years.

Methods: The study included 1488 children undergoing KRT in Poland between 2000 and 2023. Thirty-nine patients with CM-HUS and 18 with STEC-HUS were identified and analysed for incidence, KRT modality and survival.

Results: The incidence rate of CKD5 was 0.09 cases/million age-related population (marp) for STEC-HUS and 0.23/marp for CM-HUS, while no new cases have been observed in recent years. CKD5 due to CM-HUS developed significantly earlier from initial HUS manifestation than in STEC-HUS (median 0.2 vs. 9.8 years). CM-HUS was associated with younger age at initiation of KRT compared to STEC-HUS and non-HUS controls (median 6.0 years vs. 10.9 and 10.9 years), with higher risk of death (Hazard Ratio 1.92, 95% confidence interval 0.9-4.13) and worse 5-year kidney graft survival at 77%, 93% and 90%, respectively (p < 0.001).

Conclusions: In recent years, both CM-HUS and STEC-HUS have become increasingly rare causes of CKD5 in children. CKD5 due to CM-HUS in the eculizumab era and due to STEC-HUS after improving supportive treatment is exceptional. Children on KRT due to STEC-HUS had a significantly better survival, shorter waiting time for kidney transplantation and better kidney graft survival compared to the CM-HUS group.

Background: Most infants with febrile urinary tract infection (UTI) do not have an underlying anatomical risk factor. Thus, other non-anatomical risk factors should be considered. Since the most common pathogens arise from the fecal microbiota, our aim was to investigate whether the gut microbiota composition differs between febrile infants younger than 2 months with or without UTI.

Methods: In this prospective, case-control, pilot study, we performed 16S ribosomal ribonucleic acid amplicon sequencing to characterize gut microbiota of febrile neonates with and without UTI admitted to the pediatric ward at Shamir Medical Center between February 2019 and May 2021.

Results: The study cohort included 42 febrile neonates: 17 with and 25 without febrile UTI. We found a significant difference in beta diversity (i.e. between-sample/study group similarity indices) between the UTI and non-UTI group (p = 0.016). There were also distinct differences in the relative abundance of the 20 most prevalent genera. Furthermore, several genera were significantly enriched in the UTI group, with others dominating the non-UTI group. Streptococci were underrepresented in the UTI group. There was no difference in alpha diversity (i.e. within-sample diversity/richness) between groups.

Conclusion: Febrile neonates with UTI have a different fecal microbiota composition (beta-diversity), but not alpha diversity, in comparison to febrile neonates without UTI. A larger study is warranted to confirm these findings and their potential applications.

Glomerular filtration rate (GFR) can be measured directly, or estimated from biomarkers like serum creatinine and cystatin C, or both. Measuring GFR in children is cumbersome, as it requires the intravenous injection of an exogenous filtration marker like iohexol, and several blood samples to determine the concentration-time decay curve. Serum creatinine (SCr) measurement is inexpensive and is part of the routine biochemical blood tests that are commonly requested in daily clinical practice. SCr-based estimated GFR is therefore still the most widely used test to obtain information on kidney function, although SCr varies with age and sex during childhood and GFR remains nearly constant over the 2-18-year age range. These issues are partially resolved by factoring SCr by height, or rescaling SCr by the median of healthy subjects, making interpretation of SCr and eGFR more straightforward. Cystatin C has become an interesting alternative kidney biomarker, and estimating GFR from cystatin C has therefore become more important. The aim of this review is to show recent advances in measuring and estimating GFR in children.

Background: Asymptomatic, mild urinary tract dilatation (UTD) that does not resolve can progress in severity, which suggests the need for continued observation. However, no studies have investigated the factors that contribute to the non-resolution of mild UTD.

Methods: We conducted this prospective cohort study of children who were newly diagnosed with mild UTD during the neonatal period from 2013 to 2021. The patients were evaluated by periodic kidney ultrasound until 3 years of age. Sonographic reference values for kidney length were determined according to estimation formulas, and sonographic kidney volume was calculated using kidney length, width, and depth.

Results: This pilot study included 33 children with mild UTD, totaling 58 kidney units. The kidney units were graded as UTD P1 in 23 and UTD P2 in 35 units. Sonographic kidney length and volume were significantly higher for kidneys with UTD P2 units that did not resolve over 3 years than in those that resolved at 3 months, 6 months, and 1 year. The time to resolution of UTD P2 units in kidneys with a length of > 0.7 standard deviations at 3 months and > 1.2 standard deviations at 6 months was significantly longer than the time to resolution in kidneys with a length of ≤ 0.7 standard deviations at 3 months (p < 0.01) and ≤ 1.2 standard deviations at 6 months (p = 0.01).

Conclusions: Increased sonographic kidney length in UTD P2 is a prognostic factor for non-resolution of mild UTD.

Background: Very-low-birth-weight (VLBW) infants have significant risk factors for adverse health outcomes. Previous studies have focused on neurological, pulmonary, and cardiovascular complications, but the long-term outcomes of other organ functions particularly kidney function warrant further investigation. This prospective study aimed to compare kidney function between VLBW preterm and term infants at 5-6 years of age.

Methods: Participants underwent comprehensive assessments of kidney function and blood pressure. Estimated glomerular filtration rates (eGFR) for serum creatinine (Cr) and cystatin C (CysC) were calculated using the CKiD-U25 equations, and comparative analyses conducted between preterm and term groups. In the preterm group, perinatal growth rates of weight and height at various stages were monitored to investigate their potential association with kidney function.

Results: A total of 61 VLBW preterm and 40 term children participated in the study. The preterm group exhibited significantly higher serum CysC levels (0.97 vs. 0.87 mg/L, p = 0.001), lower eGFR-CysC (82.3 vs. 93.0 mL/min/1.73 m², p < 0.001), and smaller kidney length compared to the term group. Notably, 72% of VLBW preterm children exhibited abnormal eGFR-CysC levels (< 90 mL/min/1.73 m²). Preterm children exhibited significantly higher systolic and diastolic blood pressures, but growth velocities and perinatal characteristics did not significantly affect kidney function at preschool age.

Conclusions: Kidney function may be diminished in VLBW preterm children at preschool age. However, no significant effects of perinatal risk factors or growth on kidney function were observed. These findings underscore the importance of ongoing long-term monitoring of kidney health in this vulnerable population.

Objectives: To investigate the safety and efficacy of telitacicept in children with immunoglobulin (Ig) A vasculitis nephritis (IgAVN).

Methods: This is a case series of children with biopsy-confirmed IgAVN who received glucocorticoid with or without a second immunosuppressant and presented with urinary protein levels > 0.3 g/day/kg. The patients were administered telitacicept subcutaneously weekly as an adjunct to the standard treatment. The laboratory indices were assessed before and 24 weeks post-treatment, and the treatment's efficacy and side effects were analyzed.

Results: Seven patients (six males and one female) were enrolled in the study. The median age and body weight of patients were 13 years and 48 kg, respectively. The median disease duration was 29 months. After treatment with telitacicept (80 or 160 mg administered per week) until the 24th week, the 24-h urinary protein levels, percentage of CD19 + B cells, and IgA and IgM levels were decreased compared to the baseline values (P < 0.05). Serum albumin and complement C4 levels increased significantly in response to the treatment (P < 0.05). The serum creatinine, blood urea, serum total protein, IgG, and complement C3 levels and urine erythrocyte counts were not significantly different (P > 0.05) from the respective pre-treatment values. The enrolled patients did not experience any drug reactions.

Conclusions: The combination of telitacicept and the standard treatment showed good clinical effects in children with IgAVN. This treatment showed good safety and had good tolerance.

IgA nephropathy in children has a potential progression risk over decades of adult life. For this reason, pediatric nephrologists tend to treat the disease from the onset, aiming at halting the pathogenetic processes, based on expert opinion and general confidence with steroids for the lack of large pediatric controlled studies. Glucocorticosteroids are widely used, although without full comprehension of the fine molecular effects on IgAN, mostly based on trials performed in adults. In this review, a critical analysis of adult data is provided for extrapolating information useful for children, with a parallel evaluation of the results of the TESTING Trial, employing oral methylprednisolone, and of the NEFIgArd Trial, using enteric release budesonide. Patients' characteristics and the scheme of the two studies are surprisingly similar: Nefecon and methylprednisolone showed 40-50% proteinuria reduction from baseline, with a fast effect of methylprednisolone (3-6 months) and a similar effect on renal function decline. Large genome-wide studies, above-risk alleles, also discovered risk loci targetable by multiple drugs particularly those involved in the modulation of the mucosal immunity priming of B-cells toward the production of galactose deficient IgA1 (Gd-IgA1). The new KDIGO 2024 guidelines under public review in recent months will lower the proteinuria threshold for treatment to 0.5 mg/mg and consider the value of Nefecon in reducing the levels of Gd-IgAI1. The choice between old and new corticosteroids in treating children with IgAN is approaching. In the near future, the genetic data, complemented by blood and urine biomarkers, could be included in tools to guide therapeutic choices and monitoring.

Background: Artificial intelligence (AI) has emerged as a transformative tool in healthcare, offering significant advancements in providing accurate clinical information. However, the performance and applicability of AI models in specialized fields such as pediatric nephrology remain underexplored. This study is aimed at evaluating the ability of two AI-based language models, GPT-3.5 and GPT-4, to provide accurate and reliable clinical information in pediatric nephrology. The models were evaluated on four criteria: accuracy, scope, patient friendliness, and clinical applicability.

Methods: Forty pediatric nephrology specialists with ≥ 5 years of experience rated GPT-3.5 and GPT-4 responses to 10 clinical questions using a 1-5 scale via Google Forms. Ethical approval was obtained, and informed consent was secured from all participants.

Results: Both GPT-3.5 and GPT-4 demonstrated comparable performance across all criteria, with no statistically significant differences observed (p > 0.05). GPT-4 exhibited slightly higher mean scores in all parameters, but the differences were negligible (Cohen's d < 0.1 for all criteria). Reliability analysis revealed low internal consistency for both models (Cronbach's alpha ranged between 0.019 and 0.162). Correlation analysis indicated no significant relationship between participants' years of professional experience and their evaluations of GPT-3.5 (correlation coefficients ranged from - 0.026 to 0.074).

Conclusions: While GPT-3.5 and GPT-4 provided a foundational level of clinical information support, neither model exhibited superior performance in addressing the unique challenges of pediatric nephrology. The findings highlight the need for domain-specific training and integration of updated clinical guidelines to enhance the applicability and reliability of AI models in specialized fields. This study underscores the potential of AI in pediatric nephrology while emphasizing the importance of human oversight and the need for further refinements in AI applications.

Background: Idiopathic nephrotic syndrome (INS) in children is the most common glomerular disease and is characterized by recurrent relapses. There is no community consensus on the treatment of relapsing forms of nephrotic syndrome in children, unlike that for the initial presentation. To date, available treatments only enable relapsing patients to be maintained in remission, rather than modifying the course of the disease; therefore, more therapeutic trials are needed. The Société de Néphrologie Pédiatrique (SNP) decided to implement within its French centers a national coordinated long-term clinical research program for children treated for INS based on a Trials within Cohorts (TwiCs) model. The aim of this paper is to describe the PIN'SNP cohort and research program as well as the TwiCs design adapted to INS research in the French regulatory system.

Methods: This retrospective-prospective, multicenter research program will rely on a dynamic prospective cohort of children followed for an INS, known as the PIN'SNP cohort (i) to identify cases treated within SNP centers, (ii) to describe their clinical and epidemiological characteristics, and (iii) to provide a platform to nest prospective trials, and thus facilitate inclusion of patients in these future trials.

Conclusions: The PIN'SNP cohort is the first French national pediatric platform dedicated to the implementation of randomized nested trials along with longitudinal and observational studies on INS in children. The adaptation of the TwiCs design to inform all eligible patients/parents to each nested trial will facilitate methodological robustness and ethical acceptability and reinforce communication between investigators and participants.

Trial registration: number NCT04207580.