A major complication of type 1 diabetes is diabetic kidney disease (DKD). Albuminuria and impaired glomerular filtration rate are the main characteristics of DKD. Neutrophil gelatinase-associated lipocalin (NGAL) levels may rise even in the early stages of DKD, even in patients with normoalbuminuria. We present the first systematic review and meta-analysis examining the prognostic role of NGAL exclusively in pediatric patients with type 1 diabetes. A search through major databases was carried out until September 24, 2024, investigating the prognostic role of NGAL in kidney injury in pediatric patients with type 1 diabetes. A p < 0.05 was considered statistically significant. A study quality assessment was conducted using the Newcastle-Ottawa Scale. The standardized mean difference in urinary NGAL (uNGAL) levels between the type 1 diabetes group and healthy controls was statistically significant (SMD = 0.63, 95%CI [0.36,0.90]). A moderate positive relationship between uNGAL and ACR was identified (r = 0.53, 95 % CI [0.31-0.70]). The uNGAL revealed a high overall diagnostic accuracy (AUC = 0.881). Urinary NGAL appears to be a valuable biomarker for early detection and understanding of DKD in individuals with type 1 diabetes. Future clinical studies should prioritize assessing the accuracy of NGAL in identifying kidney injury in pediatric patients with type 1 diabetes and the association of NGAL with traditional biomarkers in groups with similar characteristics.

Background: Advances in neonatal care have improved survival rates in preterm neonates. However, concerns persist regarding the long-term kidney implications of prematurity. Nephrogenesis is disrupted, particularly in those born very preterm (≤ 32 weeks of gestation), increasing the risk of early kidney dysfunction and hypertension later in life. Objectives: This systematic review and meta-analysis aimed to evaluate kidney health outcomes in former very preterm children and adolescents compared to full-term peers. Data sources: A systematic literature search was conducted in MEDLINE/PubMed, Scopus, and Web of Science from their earliest available records to October 9, 2024. Study eligibility criteria: We included observational studies comparing kidney health parameters between children/adolescents born very preterm (gestational age – GA ≤ 32 weeks) and their full-term counterparts (gestational age > 36 weeks or birth weight > 2000 g) within the age range of 6 to 18 years. Participants and interventions: Children and adolescents aged 6–18 years born very preterm were compared to their full-term counterparts. The analyzed kidney function markers included serum Cystatin C, serum creatinine (sCr), estimated glomerular filtration rate (eGFR) based on sCr (Cr-eGFR), and blood pressure (systolic and diastolic, SBP/DBP). 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, subgroup and meta-regression analyses were conducted for further exploration of the outcomes. Statistical analyses were performed using R software (Version 4.3.2). Results: Thirteen studies (16 reports; 2,112 participants) were included. Very preterm children and adolescents had higher serum Cystatin C (0.05 mg/L; 95%CI: 0.02–0.08), lower Cr-eGFR (-11.87 mL/min/1.73 m ² ; 95%CI: -22.44 to -1.31), and higher SBP (1.96 mmHg; 95%CI: 0.21–3.71). Sensitivity analysis confirmed Cystatin C findings but rendered Cr-eGFR and SBP differences non-significant. Subgroup analysis showed a significant GA effect on sCr ( p < 0.0001), though the ≥ 28 weeks subgroup included only two studies. Limitations: Considerable heterogeneity across studies persisted despite sensitivity and subgroup analyses. The lack of randomized controlled trials and longitudinal studies limits result interpretation, while non-significant meta-regression findings hinder full explanation of heterogeneity. Insufficient data prevented the assessment of additional kidney function parameters. Conclusions and implications of key findings: Cystatin C was elevated in very preterm individuals compared to full-term peers, reinforcing its role as an early marker of kidney dysfunction. While differences in Cr-eGFR and SBP lost significance after sensitivity analysis, these markers remain relevant for long-term follow-up in this vulnerable population. Systematic review registration number: PROSPERO (CRD42024554702). Graphical

Background: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease associated with increased cardiovascular (CV) burden. Besides increased arterial stiffness and subclinical atherosclerosis, microvascular dysfunction is considered an important component in the pathophysiology of CV disease. However, there is a lack of data regarding the effect of multiple target organ damage (TOD) on CV health. Objectives: This study aimed to evaluate (i) the presence of microvascular changes in SLE in various vascular beds, (ii) the possible associations between the accumulation of microvascular TOD and CV risk and (iii) whether Galectin-3 represents a predictor of combined microvascular TOD. Methods: Participants underwent (i) evaluation of skin microvascular perfusion (laser speckle contrast analysis), (ii) fundoscopy (non-mydriatic fundus camera), (iii) indirect assessment of myocardial perfusion (subendocardial viability ratio) and (iv) determination of urine albumin-to-creatinine ratio (UACR). CV risk was calculated using the QResearch Risk Estimator version 3 (QRISK3). Serum Galectin-3 levels were determined. Results: Forty-seven SLE patients and fifty controls were studied. SLE patients demonstrated impaired skin microvascular reactivity (160.2 ± 41.0 vs. 203.6 ± 40.1%), retinal arteriolar narrowing (88.1 ± 11.1 vs. 94.6 ± 13.5 μm) and higher UACR levels compared to controls. Furthermore, SLE individuals had significantly higher Galectin-3 levels [21.5(6.1) vs. 6.6(6.6) ng/dL], QRISK3 scores [7.0(8.6) vs. 1.3(3.6)%] and a greater chance for microvascular dysfunction. In the SLE group, patients with multiple TOD exhibited higher QRISK3. In the multivariate analysis, the accumulation of TOD correlated with disease activity and Galectin-3 (p < 0.05). Conclusions: Our study showed for the first time that SLE patients exhibit a greater number of cases of TOD. The accumulation of TOD was associated with increased CV risk. Clinicians dealing with SLE should be aware and seek microvascular alterations.

Background: Prematurity has been linked to kidney dysfunction from infancy through adulthood. Children born very preterm are at particular risk due to interrupted nephrogenesis. However, early detection remains challenging, and a uniform monitoring strategy is lacking. Methods: This cross-sectional study involved school-aged (6–16 years) children born at ≤ 32 weeks of gestation, with no history of small for gestational age (SGA). They were further stratified by birth weight (BW): low, very low, and extremely low (LBW, VLBW, ELBW) categories. Age- and sex-matched full-term children served as controls. Anthropometry, blood pressure (BP), and kidney function were assessed, using traditional (urea; creatinine, Cr; β2-microglobulin, B2M; albuminuria) and modern biomarkers (cystatin C, CysC; symmetric dimethylarginine, SDMA). Estimated glomerular filtration rate (eGFR) based on Cr and Cr-CysC was also calculated. Statistical analysis was performed using R (version 4.3.2), with significance set at p < 0.05. Results: Eighty-one children were included: 43 preterm (77% from multiple pregnancies) and 38 controls. Compared to controls, preterm participants had higher serum cystatin C ( p < 0.001) and lower Cr-CysC-eGFR ( p < 0.001). They also had higher serum urea ( p = 0.002), but all individual values were within the normal range. No differences were observed in BP, serum Cr, Cr-eGFR, or albuminuria. ELBW children had lower body mass index (BMI) ( p = 0.048) and higher B2M ( p = 0.046) than LBW peers. Conclusions: School-aged children born very preterm may already exhibit subtle signs of kidney dysfunction, with ELBW children showing greater metabolic and renal strain. Cystatin C and Cr-CysC-eGFR appear promising biomarkers for early detection of kidney alterations in this high-risk population. Graphical

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.

Background: Skin and myocardial microvascular dysfunction in prediabetes remains underexplored, and limited studies have investigated the microcirculation in prediabetes in multiple vascular beds. This study aimed to examine microvascular alterations in patients with prediabetes, patients with type 2 diabetes mellitus (DM), and normoglycemic controls without established cardiovascular disease (CVD). Methods: In this cross-sectional study, the microcirculation was assessed using established and novel noninvasive techniques. The skin microvascular reactivity was evaluated using laser speckle contrast analysis (LASCA). The myocardial perfusion was assessed by the subendocardial viability ratio (SEVR). The retinal microvasculature was evaluated using digital nonmydriatic fundus photography, the renal microvascular damage through the urinary albumin-to-creatinine ratio (ACR), and the peripheral vasculopathy by the augmentation index (AIx). Results: Sixty-seven participants were included (22 controls, 24 with prediabetes, 21 with DM; aged: 55.9 ± 9.4 years). Patients with prediabetes and DM showed significantly reduced baseline-to-peak skin flux responses in LASCA compared with controls (p = 0.006), and lower SEVR values (p = 0.001). Moreover, no significant differences were identified in the retinal, renal, or peripheral microvascular indices. In multivariate analysis, systolic blood pressure and glucose were independently associated with skin microvascular dysfunction, while the heart rate and arteriovenous ratio were associated with the SEVR. Conclusions: In this cross-sectional study, impaired skin and myocardial microvascular function were observed in patients with prediabetes in the absence of overt CVD. These findings suggest that LASCA and the SEVR may serve as sensitive markers for the detection of early, subclinical microvascular dysfunction in prediabetes.