Search Results (51)

Background: Idiopathic nephrotic syndrome (NS) in children is characterized by urinary protein loss and potential disruptions in trace element homeostasis. The dynamic changes in zinc, copper, and magnesium levels in relation to disease activity remain incompletely defined. Objective: This study aimed to evaluate serum zinc, copper, and magnesium and urinary copper and magnesium alterations in homeostasis in pediatric nephrotic syndrome and to examine their associations with disease stage, proteinuria, disease duration, renal function, and corticosteroid response. Materials and Methods: This is a prospective cohort study involving 108 participants, including 74 pediatric patients with idiopathic nephrotic syndrome and 34 healthy controls, comprising 164 clinical and biological assessments. Serum and urinary concentrations of Zn, Cu, and Mg were analyzed, alongside clearance parameters and the fractional excretion of magnesium. Statistical analysis included non-parametric tests, Spearman correlations, ROC analysis, and multivariable logistic regression. Results: Serum zinc levels were significantly lower during active disease phases and normalized during remission (p < 0.001); however, these differences in serum zinc concentration with stages of the NS disappeared after adjustment for serum protein levels (p = 0.424), suggesting a transport deficit secondary to hypoproteinemia. Although serum zinc concentrations were also significantly reduced in patients with concomitant infection, adjustment for serum protein levels attenuated this association, and the zinc-to-protein ratio did not differ significantly according to infection status (p = 0.08). Urinary copper levels and clearance were elevated during active disease and positively correlated with proteinuria (rho = 0.35–0.38; p < 0.001); the Cu/Zn ratio varied significantly across disease stages (p < 0.001) and was associated with both disease activity and a tendency toward corticosteroid resistance. Magnesium demonstrated a pattern of tubular conservation during active phases, with elevated fractional excretion values during remission (p < 0.001) and inverse correlations with proteinuria. Disease duration, but not relapse burden, was positively correlated with serum zinc and fractional magnesium excretion and inversely correlated with serum magnesium. In the multivariable analysis, serum proteins emerged as the sole independent predictor of disease activity, while age and the Cu/Zn ratio were associated with corticosteroid resistance. Conclusions: Pediatric nephrotic syndrome induces significant alterations in zinc, copper, and magnesium homeostasis, dependent on glomerular permeability and plasma protein status. Zinc changes with stages of NS likely reflect a secondary transport defect. In contrast, zinc changes with infection likely occurred because of a shift of zinc to the intracellular compartment. Urinary copper serves as a marker of glomerular permeability and magnesium highlights tubular adaptation. The Cu/Zn ratio and magnesium handling parameters may prove clinically useful in monitoring disease activity and treatment response. Full article

Background: Pediatric idiopathic nephrotic syndrome (INS) is classified primarily by corticosteroid response, delaying identification of steroid-resistant disease and exposing children to unnecessary treatment toxicity. Novel biomarkers could enable earlier biological stratification and treatment guidance. Objectives: The study aimed to map available evidence on candidate biomarkers in pediatric INS published since 2020, with emphasis on anti-nephrin autoantibodies and their potential for clinical translation. Data Sources: PubMed/MEDLINE and Web of Science Core Collection (January 2020–October 2025), with a supplementary verification search in Scopus and Embase and manual reference screening. Eligibility Criteria: Original studies reporting circulating, urinary, or tissue-based biomarkers in children aged 0–18 years with idiopathic NS, with outcomes related to diagnosis, treatment response, relapse prediction, or monitoring. Studies in adults only, secondary NS, or animal models were excluded. Results: After screening, 34 studies met the eligibility criteria and were included, grouped into five categories: autoantibodies, urinary markers, immune cell signatures, cytokines/chemokines, and exploratory markers (metabolomics, extracellular vesicles, lipid profiles, microRNAs). Anti-nephrin IgG emerged as the most mechanistically informative marker, with seroprevalence declining across phenotypes (SSNS 68%, SDNS 28%, non-genetic SRNS 14%, genetic SRNS 2%) and positivity predicting response to intensified immunosuppression. Of the candidates reviewed, urinary NGAL and peripheral B-cell subset monitoring are the most readily implementable with existing laboratory infrastructure. Conclusions: Pediatric INS encompasses a spectrum of immune-mediated podocytopathies that may soon be distinguishable by emerging biomarker profiles. Anti-nephrin autoantibodies provide the strongest mechanistic evidence for an autoimmune podocytopathy. Full article

Objective: Idiopathic nephrotic syndrome (INS) is a rare, relapsing kidney disease. Trigger for relapses, among others, may be exposure to gluten in patients with INS and celiac disease (CD). CD is a gluten-sensitive disorder. The prevalence of CD ranges from 1% in the general population to 8% in patients with autoimmune diseases. The aim of the study was to assess the incidence of CD in patients with INS and the influence of a gluten-free diet on the course of INS. Material and Methods: A retrospective cohort study was conducted on 147 patients hospitalized between February 2020 and September 2024 in a single medical center. Patients were categorized into two groups: 98 patients with INS and 49 from the control group. The analysis included age, gender, total dose of glucocorticoids (GCs), duration of INS, serum levels of immunoglobulin class A (IgA) and G (IgG), the presence of antibodies against tissue transglutaminase (tTG) and endomysium (EMA), and urine analysis. A medical questionnaire regarding pathological symptoms during infancy and allergic diseases of patients and family members was conducted. Results: CD was diagnosed in 8% of patients with INS. A total of 66% of patients with INS and CD who followed a gluten-free diet had no or less frequent relapses. Conclusions: CD is more common in patients with INS than in the general population. A gluten-free diet in patients with INS and CD may decrease the frequency of nephrotic proteinuria relapses. CD may be oligosymptomatic, and it is important to search for it in all patients with INS. Owing to the small number of patients with CD among INS in the study, this issue requires further research. Full article

Idiopathic nephrotic syndrome (INS) is the most prevalent glomerular illness in children. Even while immunologic processes are well-established, oxidative stress is becoming more widely acknowledged as a significant factor in the etiopathogenesis of illness. Assessing its activity and treatment response may be made easier with the use of trustworthy, non-invasive indicators to track redox balance. We report on the oxidative stress levels of a 10.7-year-old boy with INS with five clinical time points in one year. The FRAS5 analyzer was used to calculate the oxidative stress index (OSI), plasma antioxidant capacity (PAT) and derivatives of reactive oxygen metabolites (d-ROMs) as biomarkers. A 4-tier oxidative state classification scheme based on d-ROM and PAT thresholds was used to interpret the values. The patient had low antioxidant defense, moderate oxidative and increased OSI at relapses, a positive transition to reduced oxidative burden and enhanced defense during remission. The order of events showed a dynamic redox response associated with glucocorticoid (GC) medication and disease activity. The potential value of d-ROM, PAT, and OSI as dynamic biomarkers for tracking disease activity, response to treatment and residual oxidative burden in pediatric INS is supported by this case. To confirm their function in more comprehensive clinical decision-making, more research is required. Full article

Idiopathic steroid-sensitive nephrotic syndrome (ISSNS) is the most common glomerular disease in children, yet its molecular mechanisms and lipid-mediated pathophysiology remain poorly understood. In this study, we performed comprehensive non-targeted metabolomic analysis of serum samples obtained from children with ISSNS during both the nephrotic and remission phases to identify metabolic alterations associated with disease status. Using liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-QTOF-MS), we profiled low-molecular-weight metabolites and identified significant alterations in several lipid classes, including sphingolipids, glycerophospholipids, and lysophospholipids. Several sphingomyelin and phosphatidylcholine species showed strong correlations with total cholesterol levels, reflecting lipid alterations consistent with the hyperlipidemic state that characterizes ISSNS. In contrast, oxidized phosphatidylcholines may more specifically reflect oxidative membrane injury and glomerular permeability changes associated with disease status. These findings highlight membrane lipid remodeling as a key feature of active disease and suggest potential lipid-based biomarkers for disease monitoring and therapeutic evaluation in pediatric ISSNS. This study provides a metabolomic framework for understanding lipid-driven mechanisms of ISSNS pathophysiology. Full article

The COVID-19 pandemic has underscored the need for telemedicine to ensure continuity of pediatric care during health emergencies. This paper presents NS-Assist, a hybrid web–mobile decision support system for managing Idiopathic Nephrotic Syndrome (INS) in children. The system combines rule-based reasoning and fuzzy inference to assist clinicians in diagnosis, treatment adjustment, and relapse monitoring, while enabling caregivers to record and track daily health data. Implemented using Spring Boot, ReactJS, and Flutter with a secure MySQL database, NS-Assist integrates medical expertise with computational intelligence to support remote decision-making. A pilot evaluation involving 40 participants, including clinicians and caregivers, showed improved communication, reduced consultation time, and enhanced follow-up continuity. These results highlight the system’s potential as a reliable and adaptable framework for pediatric telemedicine in resource-constrained and emergency settings. Full article

Background/Objectives: This study investigated the correlation of oxidative stress biomarkers with the activity of idiopathic nephrotic syndrome (INS) in Slovenian children. Methods: In this prospective study, sequential plasma and urine samples from 20 children with INS in different phases of disease activity were taken: at first disease presentation or relapse (before glucocorticoid (GC) treatment), at time of remission achievement, and after discontinuation of GC treatment. This study measured oxidative stress biomarkers, such as 8-hydroxy-2′-deoxyguanosine (8-OHdG), hexanoyl-lysine (HEL) adduct, dityrosine (DiY), and 15-isoprostane F2t, using competitive enzyme-linked immunosorbent assay (ELISA) and assessed oxidative status using the FRAS 5 analytical system, which enables rapid photometric measurement of both oxidative and antioxidant capacity from biological fluids. Two complementary tests were performed: the d-ROMs test (derivatives of reactive oxygen metabolites) and the PAT (plasma antioxidant test). The oxidative stress index (OSI) was calculated as the ratio between them. Results: Concentrations of isoprostanes in urine were statistically significantly lower in patients at first disease presentation or relapse compared to time of remission achievement. Values of PAT test in serum were significantly highest after GC treatment. Values of d-ROMs test in serum were significantly lower at time of remission achievement compared to first disease presentation or relapse. Values of 8-OHdG, HEL, DiY (in plasma and urine), isoprostanes, and OSI in plasma did not statistically significantly differ in various phases of disease activity. Conclusions: Isoprostanes in urine and PAT in serum could serve as potential biomarkers of oxidative stress and disease activity in children with INS. Full article

Membranous nephropathy (MN) is the most prevalent cause of nephrotic syndrome (NS) in adults, and it can be primary (idiopathic) with an unknown cause or secondary due to a variety of conditions (lupus, infections, malignancies, medications, etc.). It progresses to chronic kidney disease (CKD) in up to 60% of patients, and 10 to 30% develop end-stage kidney disease (ESKD). This retrospective study examines the importance of specific factors, including baseline demographic and clinical data, kidney biopsy PH findings, and selected biochemical parameters, influencing MN outcomes after 10 years of follow-up. The cohort included 94 individuals in whom a diagnosis of MN was established by percutaneous biopsy of the left kidney’s lower pole at the University Clinical Center of Serbia (UCCS) between 2008 and 2013. According to the outcomes, patients were divided into three groups: the recovery (Rec) group, with complete remission, including normal serum creatinine (Scr) and proteinuria (Prt), the group with development of chronic kidney disease (CKD), and the group with development of end-stage kidney disease (ESKD). Nephropathologists graded pathohistological (PH) results from I to III based on the observed PH findings. During the follow-up period, 33 patients were in the Rec group, CKD developed in 53 patients, and ESKD developed in 8 patients. Baseline creatinine clearance levels (Ccr), Scr, and uric acid (urate) were found to be significantly associated with the outcomes (p < 0.001). The lowest values of baseline Scr and urate were observed in the Rec group. The presence of acute kidney injury (AKI) or CKD at the time of kidney biopsy was associated with the more frequent development of ESKD (p = 0.02). Lower Ccr was associated with a higher likelihood of progressing to CKD (B = −0.021, p = 0.014), whereas older age independently predicted progression to ESKD (B = 0.02, p = 0.032). Based on this study, it was concluded that the most important biochemical and clinical factors that are associated with the outcomes of this disease are the values of Scr, Ccr, and urate and the existence of CKD at the time of kidney biopsy. Unlike most previous studies, the presence of HTN had no statistical significance in the outcome of the disease. 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

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

Idiopathic nephrotic syndrome (NS) is associated with immune dysfunction and increased susceptibility to infections. Oral health may influence systemic inflammation and disease progression. This study aimed to evaluate the salivary levels of interleukin-6 (IL-6) and interleukin-18 (IL-18) in children with NS and their association with dental health, particularly caries prevalence and the consequences of untreated caries. A cross-sectional study was conducted on 86 children aged 5–17 years, including 40 NS patients and 46 healthy controls. Clinical dental examinations assessed caries prevalence using the dmft/DMFT index and the impact of untreated caries using the pufa/PUFA index. Unstimulated saliva samples were collected, and IL-6 and IL-18 concentrations were measured using enzyme-linked immunosorbent assay. NS patients exhibited a significantly lower prevalence of active carious lesions than controls (50% vs. 72%, p = 0.039). The DMFT index was lower in the NS group (p = 0.003). Salivary IL-6 levels were significantly reduced in NS patients compared to controls (p = 0.015), while IL-18 levels showed no significant difference. IL-6 positively correlated with decayed permanent teeth and pulp/periapical tissue diseases, whereas IL-18 correlated with white spot lesions and pulp infections. IL-6 and IL-18 could serve as potential non-invasive indicators of disease progression in NS patients. Full article

Idiopathic nephrotic syndrome (INS) and other pediatric kidney diseases represent significant challenges due to their complex pathogenesis, often involving dysregulated immune responses and renal injury. Biologic therapies, defined as targeted treatments derived from living organisms, have gained traction in managing these conditions, offering a potential shift in therapeutic paradigms. This review examines the current and emerging role of biologics in treating pediatric kidney diseases, focusing on indications, contraindications, adverse effects, therapeutic positioning, and a comparison with alternative immunosuppressive treatments. Full article

(1) This study investigates the association of plasma concentrations of various cytokines and chemokines with the disease activity of idiopathic nephrotic syndrome (INS) in children in Slovenia. (2) In a prospective single-center study lasting 18 months, we took sequential plasma samples from children with INS at disease onset or relapse (prior to corticosteroid (CS) therapy), at remission, and after discontinuation of CS therapy. The Olink^®Target 48 Cytokine Panel was applied to analyze 45 analytes in the plasma samples, adhering to the manufacturer’s protocol. We performed a statistical analysis with a paired samples analysis with a t-test as well as with a non-parametric Wilcoxon correction test. (3) We included 18 pediatric patients with INS in the study. We demonstrated statistically significant differences in the concentrations of CSF1, IL4, FLT3LG, CCL19, and MMP12 in the patients at disease onset or relapse compared to those in remission, differences in the concentrations of CSF1 and IL17F in the patients at disease onset or relapse compared to those in remission after CS treatment, and differences in the concentrations of CCL19, MMP12, and CCL13 in the patients in remission compared to those in remission after CS treatment. (4) The findings support potential roles of certain cytokines and chemokines, especially CSF1, CCL19, and MMP12, in influencing the disease activity of INS. Full article

Background: Idiopathic nephrotic syndrome (INS) is the most common cause of nephrotic syndrome in children. A hallmark of the disease is the rapid remission of proteinuria following a high dose of steroids. Recurrent disease or steroid dependence are common, leading to a high steroid burden and the introduction of steroid sparing therapy. Anti-CD20 antibodies have been increasingly used with excellent results in complicated INS. Nevertheless, their use can be limited by the occurrence of infusion-related reactions (IRRs). Methods: This report discusses further treatment options for children who are intolerant to RTX and presents the first report of a successful switch to obinutuzumab (OBI) for a child with difficult-to-treat steroid-dependent nephrotic syndrome (SDNS) and RTX intolerance who was unresponsive to a desensitization protocol. Results: A 12-year-old boy with SDNS since the age of 2, was treated with steroids, cyclophosphamide and cyclosporine A (CsA). Because of the prolonged use of calcineurin inhibitors, a course of rituximab (RTX) was planned. Unfortunately, during first infusion, the boy presented with IRR. A desensitization protocol following the first unsuccessful infusion also failed. Facing the risks of long-term cyclosporine therapy, a decision was made to switch to another type of anti-CD20 antibody. Obinutuzumab infusion with a modified premedication scheme was uneventful. Conclusions: Switching therapy to obinutuzumab may be considered an option in nephrotic children who are intolerant to RTX when alternative therapies have been exhausted. The addition of montelukast to premedication and employment of desensitization protocols may decrease the risk of infusion-related reactions to anti-CD20 agents. Full article

Minimal Change Disease (MCD) is a predominant cause of idiopathic nephrotic syndrome in the pediatric population, yet presents significant clinical challenges due to its frequent relapses and steroid resistance. Despite its relatively benign histological appearance, MCD is characterized by severe proteinuria, hypoalbuminemia, and edema, which may affect patient outcomes. Current treatment strategies primarily rely on corticosteroids, which are effective in inducing remission but are associated with high relapse rates, steroid resistance, and numerous long-term side effects, underscoring the need for more targeted and effective therapeutic approaches. This narrative review synthesizes current knowledge on the pathophysiological mechanisms underlying MCD, focusing on the following three critical areas: podocyte dysfunction, immune dysregulation, and genetic susceptibility. Podocyte dysfunction, particularly involving alterations in nephrin, plays a central role in the breakdown of the glomerular filtration barrier, leading to the characteristic proteinuria observed in MCD. Immune dysregulation, including the presence of autoantibodies against nephrin and other podocyte components, exacerbates podocyte injury and contributes to disease progression, suggesting an autoimmune component to the disease. Genetic factors, particularly mutations in the NPHS1 and NPHS2 genes, have been identified as significant contributors to disease susceptibility, influencing the variability in treatment response and overall disease severity. Understanding these mechanisms is crucial for developing targeted therapies that address the underlying causes of MCD rather than merely managing its symptoms. This review highlights the need for further research into these pathophysiological processes to pave the way for more personalized and effective treatment strategies, ultimately improving patient outcomes and reducing reliance on corticosteroids. Full article