Search Results (37)

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransferase deficiency with two clinical variants (fish-eye Disease and the p.Leu364Pro mutation), lead to NS through mechanisms involving podocyte and lipid metabolism dysfunction. Congenital disorders of glycosylation and Nail–Patella Syndrome emphasize the role of deranged protein processing and transcriptional regulation in glomerular injury. The link of NS with type 1 diabetes, though rare, suggests an etiology on the basis of common HLA loci and immune dysregulation. Histopathological analysis, particularly electron microscopy, shows mainly podocyte damage, mesangial sclerosis, and alteration of the basement membrane, which aids in differentiating rare forms. Prompt recognition of these novel etiologies by genetic analysis, renal biopsy, and an interdisciplinary panel is essential to avoid delays in diagnosis and tailored treatment. 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: Podocytes are essential for kidney function, and their dysfunction can result in nephrotic syndrome, such as minimal change disease (MCD). Oxidative stress contributes to podocyte damage. We investigated the therapeutic potential of intravenously infused mesenchymal stem cells (MSCs) in a puromycin aminonucleoside (PAN)-induced rodent MCD model, focusing on oxidative stress modulation. Methods: Sprague-Dawley rats were divided into three groups: intact, PAN-Vehicle, and PAN-MSC. MCD was induced through subcutaneous PAN injection. MSCs were infused intravenously in the PAN-MSC group on day 7. Urinary albumin, serum albumin, and creatinine levels were assessed. Histological analysis of the renal cortex was performed. Podocyte protein (NPHS1, NPHS2, and PODXL) and antioxidant enzyme (SOD1, SOD2, and GPX1) levels were measured using quantitative real-time reverse-transcription PCR (qRT-PCR). Results: MSC infusion significantly reduced proteinuria and restored podocyte structure in the PAN-MSC group. Electron microscopy revealed that infused MSCs could inhibit the fusion of the foot process induced by PAN injection. qRT-PCR showed that intravenous infusion of MSCs rescued the inhibition of GPX1 expression. GFP-labeled MSCs accumulated at the podocyte injury sites. Conclusion: Systemic MSC infusion mitigates PAN-induced MCD by reducing proteinuria, preserving podocyte structure, and modulating oxidative stress via the GPX1 pathway, offering a potential therapeutic approach for nephrotic syndrome. Full article

Background and Clinical Significance: Nephrotic syndrome predisposes patients to venous thromboembolism. This case highlights the challenges of diagnosing pulmonary embolism in nephrotic syndrome patients with renal dysfunction, and emphasizes the utility of ventilation–perfusion lung scintigraphy when the contrast is contraindicated. Case Presentation: A 52-year-old male presented with fatigue, left back pain, dyspnea, and lower limb edema. The laboratory findings indicated nephrotic syndrome with significant proteinuria, hypoalbuminemia, and impaired renal function. Elevated inflammatory markers and lung infiltrates on chest CT suggested pneumonia. Despite antibiotic therapy, lung shadows, and elevated D-dimer persisted. Lower extremity ultrasound was negative for deep vein thrombosis. Due to concerns about contrast-associated nephropathy, ventilation–perfusion lung scintigraphy was performed, revealing a right lung base mismatch, leading to a diagnosis of pulmonary embolism and infarction. A kidney biopsy confirmed minimal change in disease. The patient achieved complete remission of nephrotic syndrome and was discharged on oral anticoagulation. His oral anticoagulation was discontinued after 3 months due to sustained remission and the absence of deep vein thrombosis. Conclusions: Pulmonary embolism and infarction can occur even in the absence of deep vein thrombosis. ventilation–perfusion lung scintigraphy is useful for detecting pulmonary embolism in patients with impaired renal function. 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

Background: Percutaneous ultrasound-guided renal biopsy (PRB) is a key element for diagnosis and management of several renal pathologies. We aimed to lay out the experience of our pediatric nephrology unit performing PRBs. The rationale and findings of these biopsies, safety issues and considerations of the extracted data are going to be analyzed. Methods: A retrospective study was conducted from 2008 to 2023 based on the review of the medical records of pediatric patients who underwent PRBs. In total, 216 kidney biopsies in 206 patients were performed: 115 (53.2%) during the 2008–2015 period and 101 (46.8%) during the 2016–2023 period. Results: The most frequent clinical indication for PRBs was nephritic syndrome followed by nephrotic syndrome, observed in 84 (40.8%) and 72 (34.9%) patients, respectively. The predominant diagnosis was minimal change disease (MCD) (23.3%), followed by focal segmental glomerulosclerosis (FSGS) (15%) equal to lupus nephritis (LN) (15%), and immunoglobulin A nepropathy (10.2%). Minor complications, such as subcapsular hematomas were observed in approximately 15% of patients while no therapeutic intervention was needed. Conclusions: This report is the first review of pathohistological data covering a pediatric population over a 15-year period in Greece and one of the largest in southeastern Europe, especially in the Balkan region. The main indication for a PRB was nephritic syndrome; however, MCD was the main histological diagnosis. This study emphasis the fact that PRBs constitute a safe and reliable method of diagnostic approach to kidney diseases in childhood and offers important information on therapeutic approaches as well as the prognosis of these patients. Full article

Focal segmental glomerulosclerosis (FSGS) is a major cause of nephrotic syndrome and often leads to progressive kidney failure. Its varying clinical presentation suggests potential genetic diversity, requiring further molecular investigation. This study aims to elucidate some of the genetic and molecular mechanisms underlying FSGS. The study focuses on the use of bioinformatic analysis of gene expression data to identify genes associated with familial FSGS. A comprehensive in silico analysis was performed using the GSE99340 data set from Gene Expression Omnibus (GEO) comparing gene expression in glomerular and tubulointerstitial tissues from FSGS patients (n = 10) and Minimal Change Disease (MCD) patients (n = 8). These findings were validated using transcriptomics data obtained using RNA sequencing from FSGS (n = 3) and control samples (n = 3) from the UAE. Further validation was conducted using qRT-PCR on an independent FFPE cohort (FSGS, n = 6; MCD, n = 7) and saliva samples (FSGS, n = 3; Control, n = 7) from the UAE. Three genes (TUBB6, RPL27, and PFDN5) showed significant differential expression (p < 0.01) when comparing FSGS and MCD with healthy controls. These genes are associated with cell junction organization and synaptic pathways of the neuron, supporting the link between FSGS and the neural system. These genes can potentially be useful as diagnostic biomarkers for FSGS and to develop new treatment options. Full article

There have been exciting advances in our knowledge of primary glomerular diseases and nephrotic syndromes in recent years. Beyond the histological pattern from renal biopsy, more precise phenotyping of the diseases and the use of modern nephrogenetics helps to improve treatment decisions and sometimes also avoid unnecessary exposure to potentially toxic immunosuppression. New biomarkers have led to easier and more accurate diagnoses and more targeted therapeutic decisions. The treatment landscape is becoming wider with a pipeline of promising new therapeutic agents with more sophisticated approaches. This review focuses on all aspects of entities that are associated with nephrotic syndromes with updated information on recent advances in each field. This includes podocytopathies (focal segmental glomerulosclerosis and minimal-change disease), membranous nephropathy, membranoproliferative glomerulonephritis, IgA nephropathy, fibrillary glomerulonephritis, amyloidosis, and monoclonal gammopathy of renal significance in the context of the nephrotic syndrome, but also renal involvement in systemic diseases, diabetic nephropathy, and drugs that are associated with nephrotic syndromes. Full article

Background: Prostate cancer is the most common malignancy in men. Secondary nephrotic syndrome, a feature of paraneoplastic syndrome, occurs in 11% of cases and is mainly caused by membranous glomerulopathy. The association between minimal change disease and prostate cancer is rare. Only one cause has been described in the available literature. Case presentation: We present the case of a 77-year-old patient who was admitted to our department with stage 3 acute kidney injury and with nephrotic syndrome with anasarca (creatinine: 168 µmol/L, eGFR: 33 mL/min/1.73 m², albumin: 18.5 g/L, total cholesterol: 6.86 mmol/L, urine albumin creatinine ratio: 812.7 mg/mmol). In the differential diagnosis of nephrotic syndrome, looking for a secondary cause is essential, so the parainfectious causes of nephrotic syndrome were excluded. An elevated prostate-specific antigen (10.69 ng/L) was found when screening for oncological causes, and prostate adenocarcinoma was identified on biopsy. A renal biopsy was then performed with a finding of minimal change disease. Despite the generally accepted guidelines of prostate carcinoma in that stage and age of the patient being watchful waiting, antiandrogen therapy was started with the cooperation of a urologist. There was a significant improvement in renal parameters in the patient (creatinine: 87 µmol/L, eGFR: 73 mL/min/1.73 m², albumin: 33.4 g/L, urine albumin creatinine ratio: 27.6 mg/mmol). Conclusion: This case shows the importance of multidisciplinary cooperation in the treatment of secondary causes of nephrotic syndrome. In the case of proven paraneoplastic syndrome, it is necessary to start treating the malignancy; however, in general, a conservative approach without treatment is recommended. Full article

Background: The pathogenesis of idiopathic nephrotic syndrome (INS) has not been fully explained. Among the likely factors, tumor necrosis factor - alpha (TNF-α) is considered. We aimed to evaluate the TNF-α (sTNF-α, uTNF-α) levels in the serum and urine of INS children, with the aim of determining its association with proteinuria, and of determining its usefulness as a marker of the disease severity. Methods: Fifty-one examined patients were divided into subgroups depending on the number of relapses as follows: group IA—first episode; group IB—more than two relapses, and according to treatment modality; group IIA—glucocorticosteroids (GS) alone; and group IIB—GS with immunosuppressants. Healthy age-matched children served as the control group. Results: sTNF-α and uTNF-α levels were significantly increased in active phases in the whole INS group compared to the control group. They decreased in remission, but remained significantly higher when compared to the control group. During remission in the IB group, sTNF-α levels were significantly higher than in IA, whereas, in the relapse phase, these values were similar. In the IA group, a positive correlation between proteinuria and sTNF-α was demonstrated. Conclusions: Our findings suggest that TNF-α plays a role in the development of INS, and may be used as a prognostic marker, as well as an indicator for the continuation of therapy. Additional research is required to verify this statement. Full article

The nephrotic syndrome holds significant clinical importance and is characterized by a substantial protein loss in the urine. Damage to the glomerular basement membrane or podocytes frequently underlies renal protein loss. There is an increasing belief in the involvement of the complement system, a part of the innate immune system, in these conditions. Understanding the interactions between the complement system and glomerular structures continually evolves, challenging the traditional view of the blood–urine barrier as a passive filter. Clinical studies suggest that a precise inhibition of the complement system at various points may soon become feasible. However, a thorough understanding of current knowledge is imperative for planning future therapies in nephrotic glomerular diseases such as membranous glomerulopathy, membranoproliferative glomerulonephritis, lupus nephritis, focal segmental glomerulosclerosis, and minimal change disease. This review provides an overview of the complement system, its interactions with glomerular structures, and insights into specific glomerular diseases exhibiting a nephrotic course. Additionally, we explore new diagnostic tools and future therapeutic approaches. Full article

Kidney biopsy (KB) has become essential in the nephrologist’s approach to kidney diseases, both for diagnosis, treatment, and prognosis. Our objective is to describe the preliminary results of KBs in Niger, one of the poorest countries in the world. This is a descriptive cross-sectional study that took place over 36 months in the nephrology/dialysis department of the Zinder National Hospital. Biopsy results were obtained in less than 5 working days. Patients were responsible for covering the cost of the kidney biopsy. The data collected were analyzed using Epi Info V7 software. We performed 120 kidney biopsies during the study period. The average age of the patients was 35 years ± 15.4 [5–68]. The male/female sex ratio was 2:1. Patients’ medical history included herbal medicine use in 33% of cases and high blood pressure in 27.5% of cases. Proteinuria was present at a rate of ≥3 g/24 h in 46.6% of them. The primary indication for kidney biopsy was glomerular syndrome in 62.5% of cases, including 50% with nephrotic syndrome. All kidney biopsies were performed with real-time ultrasound guidance, using an automatic gun fitted with a 16G needle. Regarding complications, macroscopic hematuria was present in 12.5% of cases. Inadequate kidney biopsy was infrequent (5.8% of cases). The most common findings were (i) glomerular diseases (58.4%), such as membranoproliferative glomerulonephritis (13.3%), focal-segmental glomerulosclerosis (10.6%), lupus nephritis (8.8%), minimal change disease (8%), and membranous nephropathy (2.7%), and (ii) tubulointerstitial changes (31.8%). Diabetic nephropathy was rare (2.6%), as was IgA nephropathy (0.9%). We have demonstrated that implementing a sustainable kidney biopsy program in a very poor country is feasible, thanks to the dedication of a specialized renal pathologist. Having a clear diagnosis can assist in properly treating these renal patients according to international guidelines, thereby delaying the progression to end-stage kidney disease. Full article

Introduction: Nephrotic syndrome (NS) remains the most common presentation of glomerular diseases in children. Moreover, NS is primarily idiopathic, accounting for 90% of cases, with an average onset age between 2 and 10 years. The objective of our study was to describe the characteristics and outcomes of NS in children from three major hospitals in one of the world’s poorest countries, Chad. Patients and Methods: This observational, cross-sectional, descriptive, and multicenter study took place over a period of 36 months (1 January 2019–31 December 2021) and was carried out in three hospitals in N’Djamena, Chad. Children aged 1–15 years presenting with NS were included in the study. Results: Out of 16,776 children hospitalized or followed up with in outpatient clinics, 24 cases of NS were identified, yielding a prevalence of 0.14%. The median age at presentation was 6.16 years (1–10). Nineteen children were male (sex ratio 3.8). Eight cases were classified as impure NS (33.3%). Edema was present in all patients, while oliguria was present in 29.16% (n = 7), and arterial hypertension was present in 20.83% (n = 5) of cases. Mean proteinuria, albuminemia, and total proteins were 2.86g/L, 19.13g/L and 30.41g/L, respectively. The median serum creatinine was 87.3 µmol/L (75–1375 µmol/L). Three patients experienced acute renal failure upon admission. Four patients had secondary NS. All idiopathic NS patients (n = 20) who had received corticosteroid therapy had a 90% response rate to steroids. Non-responsive or relapsed patients underwent kidney biopsy (n = 7), revealing focal segmental glomerulosclerosis (FSGS; n = 4) as the most common histological lesion, followed by minimal change disease (n = 2) and membranoproliferative glomerulonephritis (n = 1). The median length of hospitalization stay was 10.67 (5–27) days. None of the patients with idiopathic NS died. At the last follow-up, sixteen patients (80%) achieved long-term complete remission with normal renal function; however, four of those had subsequent relapses. One patient with secondary NS died. Conclusion: In Chad, childhood idiopathic nephrotic syndrome predominantly affects young males; steroid sensitivity is as high as 95%, and in the long-term, 80% of patients achieve remission with normal renal function. Full article

Kidney injury due to medications is a well-known clinical entity. Although drug-induced tubulointerstitial disease is commonly encountered, there are few reports in the literature associated with glomerular injury due to medications. The recognition of this type of kidney injury is crucial, as rapid discontinuation of the offending agent is critical to maximizing the likelihood of quick and effective renal function recovery. In this article, we present four cases that presented with nephrotic syndrome and were diagnosed with biopsy-proven podocytopathies, associated with exposure to a certain medication. All of them experienced complete resolution of nephrotic syndrome within days or weeks after discontinuation of the offending drug. We also present the data, which were found in a Medline search from the year 1963 until the present, regarding cases with podocytopathies associated with penicillamine, tamoxifen and the combination of pembrolizumab-axitinib, including only adult cases from the English literature. The Medline search revealed nineteen cases of penicillamine-induced minimal-change disease (MCD), one case of tamoxifen-induced MCD, and none associated with pembrolizumab-axitinib therapy. We also searched for the largest studies and meta-analyses regarding drug-induced podocytopathies after a Medline search from 1967 to the present of the English literature. Full article

Background: Vaccination is a known trigger for the appearance of immune-mediated glomerulopathies (IMG). The appearance of IMG after SARS-CoV-2 vaccination with suspected causality has been described. Our aim is to analyze the incidence of IMG flares before and after SARS-CoV-2 vaccination in our center. Methods: All persons with native kidney biopsy (KB) from January 2019 to March 2022 in our center were included in the study. We compared the incidence of IMG before and after the start of vaccination. We also collected information about whether the patients had received a SARS-CoV-2 vaccine or have suffered from COVID in the six weeks before the IMG. We also evaluated the analytical characteristics of the outbreaks. Results: A total of 386 KB were studied. Of them, 86/218 (39.4%) were IMG performed pre- and 85/168 (50.6%) post-SV (029). The incidence of idiopathic nephrotic syndrome (INS), studied separately, was also significantly increased post-vaccination (n = 18 (10.7%)) compared to pre-vaccination (n = 11 (5%)) (p = 0.036). There were no differences in the incidence of vasculitis or IgA nephropathy. Up to 17 (20%) flares occurred 6 weeks before SARS-CoV-2 vaccination and only 2 (2.4%) within the first 6 weeks after SARS-CoV-2 infection. Within those 17 flares, the most common diagnosis was IgAN (n = 5 (29.4%)); a total of 14 (82.4%) received an mRNA vaccine and 9 (52.9%) took place after the 1st vaccine dose. There were 13 cases of minimal change disease (MCD) with debut/recurrence pre-SV and 20 MCD with debut/recurrence post-SV (p = 0.002). Conclusions: The incidence of IMG, INS and MCD flares in our center increased significantly after SARS-CoV-2 vaccination. Importantly, 20% of IMG flares took place within the first 6 weeks after receiving a vaccine dose, with the first dose being the riskiest one and IgAN the most frequent diagnosis. Full article