Nikolaos Gkiourtzis

Background Delayed dimercaptosuccinic acid (DMSA) scintigraphy is increasingly selective after febrile urinary tract infection (fUTI), creating a need for reliable non-invasive risk markers. We evaluated systemic and urinary biomarkers, microbiological profiles, and ultrasound findings to predict DMSA-defined kidney scarring following a first fUTI. Methods This prospective cohort included 83 children with first fUTI or any fUTI with previous normal DMSA scintigraphy. Pre-antibiotic urine sample was analyzed for urinary kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL), pentraxin-3 (uPTX3), and creatinine (uCr). Delayed DMSA scintigraphy and voiding cystourethrography (VCUG) were clinically indicated rather than universal. Analyses included ROC curves, bootstrap confidence intervals, paired DeLong comparison, exploratory cutoffs, and sensitivity analyses. Results Dimercaptosuccinic acid scintigraphy was available in 45 children; 16 had kidney scars. Procalcitonin discriminated scarring better than CRP in the common analytic population (AUC 0.626 vs 0.429; DeLong p=0.028). Urinary pentraxin-3/uCr had the highest apparent urinary AUC (0.727), but the signal did not survive false-discovery-rate correction and was attenuated after excluding zero-coded uPTX3 values. Non-E. coli infection was strongly associated with scarring (OR 9.43, 95% CI 2.29-38.84). Among 54 children underwent VCUG, 19 were diagnosed with VUR and 17 high-grade VUR; abnormal ultrasound was associated with any VUR (OR 4.29) and high-grade VUR (OR 4.33). Exploratory biomarker cutoffs showed no marker with both high sensitivity and high specificity for scarring. Conclusions Procalcitonin outperformed CRP in scar detection, but demonstrated only moderate standalone discrimination. Neither urinary biomarkers nor internally derived cutoffs proved robust enough for independent clinical use. Risk stratification should integrate microbiology, systemic inflammation, and imaging, and requires external validation.

Background and Objectives: Children with febrile urinary tract infections (fUTIs) may be at risk for kidney scarring. Inflammatory biomarkers may predict the risk of scarring. The aim of this study was to investigate the predictive role of PCT, CRP and other markers in scarring in pediatric patients with first fUTI. Materials and Methods: The study was in accordance with the institution’s ethics committee (No. 108/2023). Included patients underwent a kidney–ureter–cyst ultrasound (US). The primary outcomes of this study were the associations of procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBC) with kidney scarring. The secondary outcomes were the associations of PCT, CRP, and WBC with vesicoureteral reflux (VUR). A p < 0.05 was considered statistically significant. Results: Sixty-five pediatric patients (1–16 years of age) with a first fUTI, from February 2023 to January 2025, were included. Sixteen patients had VUR, and thirteen patients developed kidney scarring. C-reactive protein was significantly elevated in the VUR group (p = 0.026). In a series of logistic regression analyses, abnormal US findings and severe VUR were associated with scarring (p = 0.009 and p = 0.016, accordingly). The optimal cut-off value for PCT in predicting scarring was calculated as 6.05 ng/mL (sensitivity: 36% and specificity: 97%), and for CRP as 3.62 mg/dL (sensitivity: 63.6% and specificity: 62.1%). Conclusions: This study showed a significant difference in CRP levels between the groups with and without VUR. Abnormal US findings and severe VUR were the most significant predictors of kidney scarring. Significant difference was not reached in PCT and WBC levels between the groups with and without VUR or with and without kidney scarring. The small sample size may have influenced the study’s outcomes.

Background: Children with nephrotic syndrome (NS) are frequently exposed to chronic inflammation, hypertension, and multiple metabolic abnormalities, such as hyperlipidemia, that may contribute to early development of atherosclerosis and cardiovascular disease. However, the extent of subclinical cardiovascular involvement remains unclear. Objectives: This systematic review and meta-analysis aimed to investigate the presence of subclinical atherosclerosis and cardiovascular disease in pediatric patients with NS, using carotid intima-media thickness (cIMT), carotid-femoral pulse wave velocity (c-f PWV), and left ventricular mass (LVM) index as surrogate markers. Data sources: A systematic literature search was conducted in PubMed/MEDLINE, Scopus, and Cochrane Library databases from their inception until December 20, 2024. Study eligibility criteria: Eligible studies included observational studies that evaluated early markers of atherosclerosis and cardiovascular disease in children with NS. Participants and interventions: Children and adolescents with NS under the age of 18 years were compared to healthy controls. Surrogate markers included cIMT, PWV, and LVI index. Blood pressure was evaluated as a cardiovascular risk factor. Study appraisal and synthesis methods: The Newcastle–Ottawa Scale was used to assess study quality. The mean difference with 95% confidence intervals was used for continuous outcomes. Statistical significance was set at p < 0.05. Sensitivity and subgroup analyses and meta-regression were conducted for further exploration of the outcomes. Statistical analyses were performed using R software (Version 4.3.2). Results: Sixteen studies with a total of 1461 participants (668 patients with NS and 793 healthy controls) met inclusion criteria. Children with NS had significantly increased cIMT compared to controls (MD = 0.06 mm; 95% CI: 0.05–0.07; p < 0.001), with substantial heterogeneity across studies. No statistically significant differences were observed for c-f PWV and LVM index. Moderate correlations were found between cIMT and disease duration ( r = 0.47) and number of relapses ( r = 0.45). A small positive correlation was observed between cIMT and triglycerides, but not with total or LDL cholesterol. Limitations: This meta-analysis is limited by the observational and predominantly cross-sectional nature of the included studies, substantial heterogeneity across studies, and the highly diverse study population. Furthermore, in many studies, the phenotypes of NS were poorly characterized, or grouped together, and insufficient data were provided for treatment regimens, limiting interpretation of the results. Conclusions and implications of key findings: Children with NS exhibit increased cIMT, which may be associated with increased future cardiovascular risk. However, prospective longitudinal studies are needed to determine whether these surrogate markers can predict such an association. Graphical

Tubulointerstitial damage is a common diabetic kidney disease (DKD) complication caused by diabetes mellitus. However, many patients may not present with albuminuria or impaired glomerular filtration rate (GFR), making it difficult to detect kidney dysfunction. Kidney injury molecule-1 (KIM-1) is an emerging biomarker of early DKD, reflecting tubular injury before glomerular dysfunction. We explored the association between KIM-1 and DKD in children and adolescents with type 1 diabetes (T1D). We included 10 studies with 842 participants published between 2016 and 2025. A literature search of MEDLINE/PubMed, Cochrane Library, and Scopus was conducted from inception through January 5, 2026. The mean difference with a 95% confidence interval (CI) was calculated, and a P-value of <0.05 was considered statistically significant. A quality assessment of the included studies was conducted using the Newcastle-Ottawa Scale. In the meta-analysis of four studies, the urinary KIM-1 (uKIM-1)/creatinine ratio was elevated before changes in estimated GFR (95% CI, 0.02–0.48; P=0.03). This review suggests that uKIM-1/creatinine ratio and uKIM-1 may act as promising tubular biomarkers associated with early kidney injury in pediatric patients with T1D. However, further data are needed to clarify their role in pediatric DKD.

Resumo Introdução: Doença renal diabética (DRD) é uma das principais complicações do diabetes mellitus tipo 1 (DM1). Na prática clínica, albuminúria e taxa de filtração glomerular estimada (TFGe) reduzida são as principais características da DRD. Estudos posteriores revelaram que a lesão intersticial também é observada quando ocorre DRD. Portanto, a aplicação de um biomarcador para a detecção precoce da DRD foi fundamental. Esta revisão sistemática teve como objetivo resumir a literatura sobre o papel prognóstico da cistatina C na injúria renal em crianças e adolescentes com DM1. Métodos: Desde o início até 24 de setembro de 2024, realizou-se extensa pesquisa bibliográfica nos principais bancos de dados (MEDLINE/PubMed, Cochrane Library e Scopus) para investigar o papel prognóstico da cistatina C na injúria renal em pacientes pediátricos com DM1. A diferença média foi utilizada para desfechos contínuos com IC95%. Um valor p < 0,05 foi considerado estatisticamente significativo. A avaliação da qualidade dos estudos incluídos foi realizada por meio da Escala de Newcastle-Ottawa. Resultados: Incluímos onze estudos com 2.199 participantes nessa revisão sistemática. A meta-análise incluiu quatro estudos. Não houve diferença estatisticamente significativa nos níveis séricos de cistatina C entre os pacientes com DM1 e o grupo controle. Conclusão: Embora estudos individuais tenham demonstrado algum benefício do uso da cistatina C sérica para o prognóstico de DRD em pacientes pediátricos com DM1, a meta-análise dos estudos incluídos não alcançou significância estatística. Estudos clínicos futuros devem concentrar-se no papel prognóstico da cistatina C (sérica e urinária) na identificação de injúria renal em pacientes pediátricos com DM1.

Introduction: Diabetic kidney disease (DKD) is a major complication of type 1 diabetes mellitus (T1D). In clinical practice, albuminuria and reduced estimated glomerular filtration rate (eGFR) are the main characteristics of DKD. Later studies revealed that interstitial damage is also observed as DKD occurs. Therefore, the application of a biomarker for early DKD detection was critical. This systematic review aimed to summarize the literature about the prognostic role of cystatin C in kidney injury in children and adolescents with T1D.

Background: Neutrophil extracellular traps (NETs) are granule- and nucleus-derived structures that support innate immunity. While the contribution of NETs to adult infections and autoimmune diseases is well studied, evidence in children is still inconsistent. This review aimed to summarize current findings on NETs in pediatric infections. Methods: This study followed the Cochrane Handbook for Systematic Reviews of Interventions and adhered to the PRISMA guidelines. A search was conducted in major databases (MEDLINE/PubMed and Scopus) from inception until 5 September 2025. The study quality was evaluated using the modified Newcastle–Ottawa Scale. Results: Eleven studies were included in the systematic review. In respiratory disease, the role of NETs was well described and their formation correlated with severity. Patients with febrile urinary tract infections showed elevated urinary NET-associated markers. In COVID-19 infection, NET levels were unchanged in uncomplicated cases but elevated in multisystem inflammatory syndrome in children. Findings in sepsis were inconsistent. Conclusions: This systematic review presents the published evidence on NET formation in the pediatric population, assessing the current knowledge and identifying the gaps to guide research. Future studies should aim to standardize NET detection methods, evaluate their prognostic value in large prospective cohorts, and explore the various NET-associated mechanisms in children.

Ureteropelvic junction obstruction (UPJO) is a major cause of obstructive uropathy in pediatric patients. However, the optimal management remains controversial. We aimed to summarize the evidence comparing surgical versus conservative treatment. We searched MEDLINE/PubMed (2016 to 31 October 2024) and the Cochrane Central Register of Controlled Trials (CENTRAL) on 31 October 2024. The primary outcome was split renal function (SRF). Results were summarized in a structured table. Study quality was assessed using the ROBINS-I tool and the level of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. Our search resulted in 2.251 reports. We included two non-randomized interventional studies with 136 patients. One study reported no statistically significant difference in SRF between the study groups after 1 year of follow up, while the second study reported higher SRF in surgical group 6 months postoperatively. The studies were judged to have a serious risk of bias, and the quality of evidence was rated as very low. The paucity of eligible data precluded the performance of a meta-analysis. Our findings could not support clinical recommendations. This study highlights the lack of high-quality evidence that will come from large, prospective, well-designed trials comparing surgical intervention to updated conservative treatment options.

Myositis ossificans (MO) is currently defined as a self‐limiting ossifying lesion affecting any extra‐skeletal soft tissue type but mostly afflicting skeletal muscles. The pathogenetic mechanism of the disease is incompletely understood, especially in paediatric cases, and has been rarely described in neonates. Ossifying myositis related to chronic kidney disease (CKD) and vitamin D deficiency has been well documented in adults with CKD‐mineral bone disease (CKD‐MBD), but no paediatric cases have been described. Therefore, we describe a neonate with ossifying myositis following CKD and vitamin D deficiency, with complete remission after adequate treatment. An extremely premature neonate was admitted to our neonatal intensive care unit and presented with acute kidney injury and vitamin D deficiency in the first days of life. An x‐ray and computed tomography scan detected muscle ossification of the iliopsoas, gluteus maximus and thigh muscles. Whole‐body bone scintigraphy revealed a pathological increase in osteoblastic activity and a change in bone morphology and confirmed the persistence of muscle ossification after initial treatment. Treatment with alfacalcidol and cholecalciferol led to gradual clinical and laboratory improvement. A biopsy was not performed since the symmetrical lesions of the affected muscles confirmed by x‐rays, CT and bone scintigraphy ruled out the suspicion of malignancy. So far, neonatal MO related to CKD has not been described in the literature stressing the diagnostic and treatment challenges.

Background: Children with febrile urinary tract infections (fUTI), especially those with acute pyelonephritis (APN) and vesicoureteral reflux (VUR), may face several complications, especially kidney scarring. Different biomarkers, such as urinary neutrophil gelatinase-associated lipocalin (uNGAL) and procalcitonin (PCT), have been studied for predicting kidney scarring without the need for a DMSA scan. Objectives: This systematic review and meta-analysis examines the role of biomarkers in pediatric patients with a history of fUTI and their prognostic value in the diagnosis of APN and prediction of kidney scarring. Data sources: A search through major databases (MEDLINE/PubMed and Scopus) was conducted from inception until January 2, 2025. The mean difference (95% CI) was applied. A p < 0.05 was considered statistically significant. Results: The systematic review included 2300 participants from 28 studies. Procalcitonin and uNGAL were higher in individuals with scarring after a fUTI episode compared to those without scarring ( p = 0.035 and p < 0.0001, respectively). In addition, PCT was higher in patients with APN compared to those with lower UTI ( p < 0.0001). Finally, the good and moderate overall diagnostic accuracy (I ² = 29.8%) of PCT in predicting APN (AUC: 0.861) and uNGAL (I ² = 16.8%) in predicting kidney scarring after an episode of fUTI (AUC: 0.74), respectively, should be considered. Conclusions: This study showed that PCT and uNGAL can detect APN and kidney scarring after fUTI. More studies should be conducted exploring the role of other biomarkers in scarring after an episode of fUTI in pediatric patients with or without VUR. Graphical