Search Results (439)

Background and Objectives: The long-term renal and cardiovascular effects of neonatal acute kidney injury (AKI) in preterm infants remain unclear. This study investigated whether neonatal AKI leads to persistent subclinical kidney injury and blood pressure changes in school-aged children born preterm. Methods: In this prospective cohort, preterm-born children (≤35 weeks’ gestation) with (n = 19) and without (n = 38) neonatal AKI were evaluated at 7–12 years. A term-born control group (n = 44) was included for biomarker comparison. Assessments included perinatal data, anthropometry, office and ambulatory blood pressure monitoring (ABPM), and renal ultrasonography. Kidney function was evaluated using serum creatinine (sCr), cystatin C, and estimated glomerular filtration rate (eGFR). Tubular injury was assessed using urinary kidney injury molecule-1/Cr (KIM-1/Cr), neutrophil gelatinase-associated lipocalin/Cr (NGAL/Cr), and trefoil factor 3/Cr (TFF3/Cr) ratios, as well as serum TFF3. Results: Conventional kidney function markers were similar among groups. However, the AKI group had higher serum cystatin C, lower cystatin C–based eGFR, and elevated urinary KIM-1/Cr and NGAL/Cr compared to no-AKI and term controls. Serum TFF3 was also higher in the AKI group. ABPM revealed higher nocturnal systolic blood pressure and blood pressure load in the AKI group. Kidney size did not differ between preterm subgroups. Conclusions: Neonatal AKI in preterm infants is associated with subtle alterations and potential renal stress or injury at school age, detectable only with sensitive biomarkers and ABPM. Further prospective studies are needed to validate these biomarkers and determine their role in predicting long-term outcomes in preterm infants with neonatal AKI. Full article

Nephrogenic diabetes insipidus (NDI) is a rare hereditary disorder characterized by renal resistance to arginine vasopressin (AVP), resulting in the kidneys’ inability to concentrate urine. Approximately 90% of NDI cases follow an X-linked inheritance pattern and are associated with pathogenic variants in the AVPR2 gene, which encodes the vasopressin receptor type 2. The remaining 10% are attributed to mutations in the AQP2 gene, which encodes aquaporin-2, and may follow either autosomal dominant or recessive inheritance patterns. We present the case of a male infant, younger than nine months of age, who was clinically diagnosed with NDI at six months. The patient presented recurrent episodes of polydipsia, polyuria, dehydration, hypernatremia, and persistently low urine osmolality. Despite adjustments in pharmacologic treatment and strict monitoring of urinary output, the clinical response remained suboptimal. Given the lack of improvement and the radiological finding of an absent posterior pituitary (neurohypophysis), the possibility of coexistent central diabetes insipidus (CDI) was raised, prompting a therapeutic trial with desmopressin. Nevertheless, in the absence of clinical improvement, desmopressin was discontinued. The patient’s management was continued with hydrochlorothiazide, ibuprofen, and a high-calorie diet restricted in sodium and protein, resulting in progressive clinical stabilization. Whole-exome sequencing identified a novel homozygous missense variant in the AQP2 gene (c.398T > A; p.Val133Glu), classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) criteria: PM2 (absent from population databases), PP2 (missense variant in a gene with a low rate of benign missense variation), and PP3 (multiple lines of computational evidence supporting a deleterious effect)]. NDI is typically diagnosed during early infancy due to the early onset of symptoms and the potential for severe complications if left untreated. In this case, although initial clinical suspicion included concomitant CDI, the timely initiation of supportive management and the subsequent incorporation of molecular diagnostics facilitated a definitive diagnosis. The identification of a previously unreported homozygous variant in AQP2 contributed to diagnostic confirmation and therapeutic decision-making. The diagnosis and comprehensive management of NDI within the context of polyuria-polydipsia syndrome necessitates a multidisciplinary approach, integrating clinical evaluation with advanced molecular diagnostics. The novel AQP2 c.398T > A (p.Val133Glu) variant described herein was associated with early and severe clinical manifestations, underscoring the importance of genetic testing in atypical or treatment-refractory presentations of diabetes insipidus. Full article

Cystinosis is a rare systemic disease characterized by the accumulation of cystine in tissues, leading to multi-organ damage. Infantile nephropathic cystinosis is the dominant and severe form of cystinosis with critical renal manifestations that require kidney transplantation at an early age if left untreated. Cysteamine, the lifelong cystine-depleting therapy, is the mainstay treatment of nephropathic cystinosis. Cysteamine prevents cystine crystal formation and delays disease progression. While the initially introduced cysteamine consists of an immediate-release (IR) formulation, a delayed-release (DR) formulation has been developed with a simplified dosing regimen (Q12H instead of Q6H) and an improved quality of life while maintaining comparable efficacy. Due to the rare incidence of the disease and lack of international guidelines, diagnosis and treatment initiation are oftentimes delayed, leading to a poor prognosis. Pediatric and adult nephrologists from Kuwait, Saudi Arabia, the United Arab Emirates (UAE), and Qatar, in addition to one international expert from Amsterdam, convened to share their clinical experience, reflecting on the challenges encountered and therapeutic approaches followed in the management of nephropathic cystinosis in the Gulf Cooperation Council (GCC) region. Experts completed a multiple-choice questionnaire and engaged in structured discussions, where they shed light on gaps and limitations with regard to diagnostic tests and criteria to ensure early diagnosis and timely treatment initiation. Based on available literature, experts suggested an algorithm to help guide nephropathic cystinosis management in the GCC. It is highly recommended for patients who do not tolerate IR-cysteamine and do not adhere to IR-cysteamine treatment to switch to DR-cysteamine. Given the systemic nature of the disease, a multi-disciplinary approach is required for optimal disease management. Full article

Chronic kidney disease (CKD) is a progressive condition which still leads to significant morbidity and mortality among patients at all ages. Its proper management should be focused on slowing down the disease sequelae, as well as establishing an early diagnosis and treatment of its complications. Eotaxin is a potent, selective eosinophil chemoattractant, which is reported to have an impact on various kidney diseases. Nevertheless, data regarding the potential correlation between eotaxin and CKD in a pediatric population is still scarce. This study aims to assess the concentration of eotaxin in children with CKD and evaluate potential correlations with selected biochemical markers and disease occurrence. Both serum and urine eotaxin concentrations were markedly higher in children with CKD compared to healthy controls. Moreover, Receiver Operating Characteristic (ROC) curves have shown that serum eotaxin and urine eotaxin levels demonstrated high sensitivity and high specificity for the allocation of patients to the study and control groups. The authors advanced a thesis that eotaxin might serve as a marker of CKD occurrence in a pediatric population. Such a research design is innovative, since it has not been analyzed in the literature yet. However, further studies are required. Full article

Idiopathic childhood nephrotic syndrome is a common glomerulopathy comprising proteinuria, hypoalbuminemia, and edema. Podocyte dysfunction is central to this disease process. Extracellular vesicles are released from stressed cells and can represent a molecular snapshot of the parent cell of origin. We previously showed that urinary large extracellular vesicles (LEVs) derived from podocytes are increased in patients with nephrotic syndrome relapse. Here, we investigated the role of mitochondrial DNA (mtDNA) within LEVs both in vitro and in vivo, revealing the novel finding that podocytes release LEVs containing mtDNA, driven by mitochondrial stress. A puromycin aminonucleoside nephrosis rat model showed foot process effacement on electron microscopy and urinary LEVs with significantly increased mtDNA. Prednisolone, which drives remission in nephrotic syndrome in children, attenuated mitochondrial stress and reduced the amount of mtDNA content within LEVs in vitro. Lastly, urinary LEVs from children with nephrotic syndrome also contain mtDNA, and it is the podocyte LEV-fraction which is preferentially enriched. Overall, these data support a potential mechanism of podocyte mitochondrial stress in non-genetic, idiopathic pediatric nephrotic syndrome. Full article

Objectives: Acute pyelonephritis (APN) caused by extended-spectrum β-lactamase (ESBL)-positive Enterobacteriaceae poses a growing therapeutic challenge in children, as carbapenems remain the mainstay of treatment even when susceptibility to alternative agents such as amikacin is demonstrated. However, the widespread and inappropriate use of carbapenems can lead to carbapenem resistance. The aim of this study was to compare the clinical efficacy of amikacin and carbapenems in the management of pediatric acute pyelonephritis caused by ESBL-positive Enterobacteriaceae. Methods: We analyzed cases of pediatric acute pyelonephritis caused by ESBL-positive Enterobacteriaceae that were treated with either carbapenems or amikacin over a two-year period. This study compared microbiological cure, clinical improvement, and recurrence rates across the amikacin and carbapenem treatment groups. Results: Fifty-five patients were evaluated. The median age of the patients was 3 years (range, 0.1–13 years). The causative agents were E. coli in 43 cases (78.2%) and Klebsiella spp. in 12 cases (21.8%). All were susceptible to both carbapenem and amikacin in vitro. Twenty patients (36.3%) received a carbapenem and thirty-five (63.7%) received amikacin. Twenty-four (43.6%) had an underlying urological disease. No difference was observed between the groups in terms of microbiological cure, clinical improvement, or recurrence rates. Conclusions: Amikacin may be a potential alternative to carbapenems for treating pediatric ESBL-positive APN when in vitro susceptibility is confirmed. Full article

Background: Ambulatory blood pressure monitoring (ABPM) is increasingly recognized as a more reliable indicator of blood pressure status in children than clinic-based measurements, with superior predictive value for cardiovascular morbidity and mortality. However, evidence on the clinical utility of ABPM-derived indices, such as pulse pressure (PP), pulse pressure index (PPI), rate pressure product (RPP), ambulatory arterial stiffness index (AASI), and average real variability (ARV), remains underexplored in the pediatric population, particularly among children with chronic kidney disease (CKD). Objective: To evaluate the correlation between ABPM-derived indices in children, with a subgroup analysis comparing those with and without CKD. Secondary objectives included identifying factors associated with AASI and ARV and assessing their utility in cardiovascular risk stratification. Methods: In this bicentric cross-sectional study, 70 children (41 with CKD and 29 controls) were enrolled. ABPM indices (PP, PPI, RPP, AASI, and ARV) were calculated, and both descriptive and inferential statistical analyses, including linear regression, were performed. Results: Systolic and diastolic hypertension were significant predictors of elevated ARV (p < 0.05), while body mass index (BMI) and glomerular filtration rate (GFR) were positively associated with AASI (p < 0.05). Use of angiotensin-converting enzyme inhibitors (ACEIs) was associated with reduced arterial stiffness (p = 0.02). Significant differences were observed in weight, BMI, PP, and PPI between the CKD and non-CKD groups, with ABPM demonstrating greater sensitivity in detecting vascular health markers. Conclusions: ABPM-derived indices, particularly PP, PPI, and ARV, show promise in improving cardiovascular risk assessment in children. These findings support the broader use of ABPM metrics for refined cardiovascular evaluation, especially in pediatric CKD. Full article

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder primarily affecting motor neurons. Emerging evidence suggests it also involves multiple organs, including potential cardiac manifestations. This study aimed to evaluate cardiac abnormalities in pediatric SMA patients compared to age-matched healthy controls, providing insight into underlying cardiomyopathy in this population. A total of 126 children were included in the study, with 63 SMA patients and 63 age-matched controls. We conducted clinical examinations, standard electrocardiography (ECG), and cardiac ultrasound (CUS) in all patients. Electrocardiographic analysis revealed a higher prevalence of sinus tachycardia in the SMA group and significantly deeper Q waves, indicating possible myocardial involvement. Echocardiographic findings demonstrated a significant reduction in left ventricular mass and left ventricular mass index in SMA patients compared to controls, despite normal systolic function. Statistical analysis confirmed that SMA diagnosis was an independent predictor of reduced myocardial mass, suggesting a distinct cardiac phenotype in SMA patients. This study provides new evidence of subclinical cardiac involvement in SMA, characterized by reduced myocardial mass, altered electrocardiographic parameters, and increased sinus tachycardia. These findings suggest a previously unrecognized form of cardiomyopathy in SMA that differs from cardiac manifestations typically seen in other neuromuscular disorders. Full article

Background and Objectives: The nephrotic syndrome (NS) is the most common acquired childhood kidney disease. Steroids represent the cornerstone of the therapeutic strategy, representing the first-line approach, but optimal therapeutic management is debated. This study aimed to compare different steroid therapeutic management protocols. Patients and Methods: A total of 140 NS pediatric patients were enrolled retrospectively. All the kids were divided among three different groups according to the three different steroid therapeutic schemes: 2240 mg/m² (group 1), 3360 mg/m² (group 2), or 3640 mg/m² (group 3) and divided in frequently relapsing (FR-NS) or steroid-dependent (SD) NS. Results: Within group 1, 50% of the population developed FR-NS; 100% of those kids were between 2 and 6 years old. Within the second group, 54% of the patients developed FR-NS, and 83% of these kids were between 2 and 6 years old, i.e., 45% of the group population. Within group 3, 45% of the patients developed FR-NS, and 70% of these kids were among 2 and 6 years old, i.e., 32% of the group population. This group exhibits the lowest percentage (42%) of patients in the highest relapse category (≥5 relapses) compared to the other protocols, indicating that this protocol might be more effective at reducing the number of frequent relapses. No specific predictor factors of FR- or SD-NS were revealed in the studied cohort. Conclusions: A longer steroid scheme does not correlate with a better outcome, nor does it reduce the number of relapses or prevent steroid failure. Full article

Background: Kidney transplantation is the treatment of choice for pediatric patients with end-stage kidney disease. However, transplantation in children weighing < 15 kg remains challenging due to limited donor availability and higher surgical and medical risks. We report our 35-year single-center experience in this population, focusing on perioperative and long-term outcomes. Methods: We retrospectively analyzed kidney transplants performed from 1987 to 2023 in children weighing < 15 kg. Data on demographics, donor type, complications, immunosuppression, and outcomes at 2, 5, and 10 years (including survival, graft function, rejection, infections, and urological issues) were collected. Outcomes were compared between deceased and living donors and between recipients weighing < 10 kg and ≥10 kg. Results: Ninety-six transplants were included (mean age 3.3 years; mean weight 11.1 kg), 80 from deceased and 16 from living donors. Most patients (69.8%) had been treated with peritoneal dialysis. Median follow-up was 120 months. Patient survival was 95.8%; graft survival was 78.1%. Eight grafts (8.3%) were lost to renal vein thrombosis, all in deceased-donor recipients (p = 0.60). Preserved renal function (eGFR > 60 mL/min/1.73 m²) declined from 80.4% at 2 years to 66.0% at 5 years and 18.0% at 10 years. Graft survival at 10 years was significantly lower in children < 10 kg vs. ≥10 kg (49.6% vs. 80.3%, p = 0.003). CAKUT was associated with higher urological complication rates (p = 0.017). No significant differences emerged between living and deceased donor groups. Conclusions: Transplantation in children < 15 kg is feasible with good outcomes, but those <10 kg present lower graft survival at 10 years. Multidisciplinary assessment and center experience are key to optimizing results. Full article

Hemolytic uremic syndrome (HUS), a thrombotic microangiopathy primarily affecting the kidneys, can also involve the central nervous system (CNS), often leading to significant morbidity and mortality. Neurologic manifestations are among the most severe extra-renal complications, particularly in children and during outbreaks of Shiga toxin-producing Escherichia coli (STEC)-associated HUS (typical (tHUS)). This review explores the clinical spectrum, pathophysiology, diagnostic workup, and age-specific outcomes of neurologic involvement in both typical (tHUS) and atypical (aHUS). Neurologic complications occur in up to 11% of pediatric and over 40% of adult STEC-HUS cases in outbreak settings. Presentations include seizures, encephalopathy, focal deficits, movement disorders, and posterior reversible encephalopathy syndrome (PRES). Magnetic resonance imaging (MRI) commonly reveals basal ganglia or parieto-occipital lesions, though subtle or delayed findings may occur. Laboratory workup typically confirms microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and kidney damage, with additional markers of inflammation or metabolic dysregulation. Eculizumab is the first-line treatment for aHUS with CNS involvement, while its utility in STEC-HUS remains uncertain. Although many children recover fully, those with early CNS involvement are at greater risk of developing epilepsy, cognitive delays, or fine motor deficits. Adults may experience lingering neurocognitive symptoms despite apparent clinical recovery. Differences in presentation and imaging findings between age groups emphasize the need for tailored diagnostic and therapeutic strategies. Comprehensive neurorehabilitation and long-term follow-up are crucial for identifying residual deficits. Continued research into predictive biomarkers, neuroprotective interventions, and standardized treatment protocols is needed for improving outcomes in HUS patients with neurological complications. Full article

Background: Neonates, particularly those born prematurely or with low birth weight, face an elevated risk of developing Acute Kidney Injury (AKI) due to various factors. Perinatal and maternal considerations, often linked to preterm delivery, contribute to this heightened risk. Methods: A retrospective study of neonates admitted to the intensive care unit at a single Israeli Hospital who were diagnosed as having AKI. The study includes follow-up data on these children. Results: During the study period, 971 neonates were admitted to the Pediatric Intensive Care Unit (PICU), and 47 cases had a documented diagnosis of AKI. Thirty-four of them had available long-term data and were included in this analysis. A total of 13 out of 26 subjects with available blood pressure measurements had high blood pressure for their age percentile compatible with the definition of hypertension, and 6 out of 34 (17.6%) had proteinuria. Conclusions: These findings underscore the importance of increased clinical awareness and structured long-term follow-up for neonates who experience AKI. Full article

Background/Objectives: Type 1 diabetes (T1D) in children is associated with increased cardiovascular risk, partly due to coexisting blood pressure (BP) disturbances. Ambulatory blood pressure monitoring (ABPM) is recommended for detecting subtle BP abnormalities, yet the relationship between glycemic control, T1D duration, and specific BP disturbances remains unclear. This study evaluated associations between HbA1c levels, T1D duration, and ABPM-derived BP parameters in a pediatric population with T1D. Methods: We included 357 children and adolescents (aged 7–18.8 years) with T1D treated at a tertiary center. All participants underwent 24 h ABPM. Glycemic control was assessed using HbA1c; values > 6.5% were considered suboptimal. We analyzed associations between HbA1c, T1D duration, and various BP parameters, including daytime and nighttime systolic and diastolic BP, nocturnal dipping, and hypertension defined by ABPM criteria. Logistic regression analyses were performed to identify independent predictors of elevated HbA1c. Results: Arterial hypertension was confirmed in 10% of patients, and 41% showed a non-dipping BP profile. There were no significant differences in HbA1c or T1D duration between dippers and non-dippers. However, patients with HbA1c > 6.5% had significantly higher 24 h diastolic BP and were more likely to meet hypertension criteria (p = 0.009). In univariate regression, both longer T1D duration (OR = 1.086; p = 0.033) and higher 24 h diastolic BP (OR = 1.065; p = 0.0068) were associated with elevated HbA1c. Both remained significant in multivariate analysis. Conclusions: Impaired glycemic control in children and adolescents with T1D was independently associated with higher 24 h diastolic BP and longer diabetes duration. Full article

Background and Aim: Pneumococcal pneumonia is a major cause of death globally, emphasizing the importance of vaccination, especially in low- and middle-income countries. In Iran, the 13-valent pneumococcal conjugate vaccine (PCV13) is available exclusively through private healthcare systems, resulting in a lack of studies on the prevalence of Streptococcus pneumoniae (S. pneumoniae) serotypes among vaccinated children. This research aimed to explore and compare the prevalence of nasopharyngeal pneumococcal carriage, serotype distribution, and antibiotic resistance patterns in healthy PCV13-vaccinated and -unvaccinated children. Methods: From August 2023 to November 2024, a multi-center, cross-sectional observational study was conducted in Tehran, Iran. This study included 204 nasopharyngeal samples collected from children aged from 18 to 59 months, involving both cases of children vaccinated with PCV13 and unvaccinated populations. S. pneumoniae was identified through a combination of culture methods and biochemical tests, confirmed by real-time PCR. Serotyping was achieved using cpsB sequencing, and the minimum inhibitory concentration method was employed to assess antibiotic resistance. Results: This study revealed similar S. pneumoniae carriage rates between PCV13-vaccinated and -unvaccinated Iranian children (20.6% vs. 21.6%). Serotypes 23F and 19F were prevalent in unvaccinated children, while 15B/15C was more prevalent in PCV13-vaccinated children. The included S. pneumoniae serotypes in PCV13 were detected more in the unvaccinated group. PCV13-vaccinated children exhibited no penicillin-resistant pneumococcal isolates, although four isolates were non-susceptible in unvaccinated children. Both groups showed substantial resistance to erythromycin and SXT. Previous respiratory infections, daycare attendance, residence in Tehran, and a history of antibiotic consumption increased the risk of pneumococcal carriage. Conclusions: PCV13 vaccination influences pneumococcal serotype distribution and antimicrobial susceptibility, although there was no significant difference regarding carriage rates between vaccinated and unvaccinated groups. These findings highlight the critical importance of vaccination in reducing invasive serotypes and antimicrobial resistance in children under five years old, emphasizing the importance of national PCV vaccination programs alongside continuous serotype surveillance. Full article

Background/Objective: Voiding cystourethrography is the gold-standard diagnostic tool for detecting vesicoureteral reflux and is commonly requested by pediatricians, pediatric nephrologists, emergency pediatricians, and pediatric urologists. However, VCUG is invasive, exposes patients to radiation, and carries a risk of iatrogenic urinary tract infection (UTI). This study aimed to assess the correlation between VCUG findings and factors such as age, gender, referring specialist, and clinical indication for the procedure to identify opportunities to reduce unnecessary VCUG examinations. Methods: A retrospective analysis of 197 pediatric patients who underwent VCUG over 12 months at the Institute for Child and Youth Health Care of Vojvodina was conducted. Results: The Mann–Whitney U test showed no statistically significant age difference between patients with normal (median: 2.5 years) and pathological (median: 3 years) VCUG findings (Z = −0.415, p = 0.678). The chi-square test showed that patients with a single urinary tract infection (10 patients) and other clinical indications (24 patients) had a higher chance of normal VCUG findings (0.041 and 0.011, respectively). Binary logistic regression analysis showed that patients referred by pediatric urologists were 2.06 times more likely to have pathological VCUG findings than those referred by pediatric nephrologists (p = 0.013, OR = 2.059; 95%CI: 0.166–3.634). Regarding clinical indications, the chance that VCUG findings would be normal was 2.7 times higher in patients with other indications than in patients with recurrent UTIs (p = 0.038, OR = 2.729; 95% CI: 1.055–7.059). Conclusions: Pediatric urologists tend to refer patients for VCUG more selectively than pediatric nephrologists. Avoiding VCUG in cases of a single UTI or non-specific clinical indications could significantly reduce the number of unnecessary procedures, minimizing patient exposure to radiation and potential complications. Full article