Steroid-resistant Nephrotic Syndrome Research Articles

Low-density lipoprotein apheresis for refractory lupus nephritis: A case demonstrating marked improvement in proteinuria, hematuria, and renal function.

Systemic lupus erythematosus (SLE) predominantly involves the kidneys, causing lupus nephritis. Patients with diffuse proliferative lupus nephritis frequently experience poor outcomes despite advances in immunosuppressive therapies. Low-density lipoprotein apheresis (LDL-A) has been a potential therapeutic option for steroid-resistant nephrotic syndromes, but its efficacy in lupus nephritis remains unknown. Here, we report the case of a 26-year-old female patient with SLE and renal pathology society classification IV + Ⅴ (G) A/C lupus nephritis who developed refractory nephrotic syndrome, severe hematuria, and declining renal function. Initial induction therapy was insufficient. Consequently, LDL-A significantly improved proteinuria, hematuria, and renal function. The urinary protein-to-creatinine ratio decreased from 7.15 g/gCr to 0.610 g/gCr, and hematuria dropped from >100 to 10-19 erythrocytes per high-power field. Additionally, complement levels were improved and anti-double-stranded DNA antibody titers were reduced. Ascribing these improvements solely to LDL-A remains challenging, but the rapid proteinuria and hematuria reduction within 48 h indicates a substantial contribution of LDL-A to the clinical response. The effluent from LDL-A contained not only LDL cholesterol but also measurable amounts of IgG and IgM, which may have contributed to the reduction in lupus nephritis activity. This case represents the first report of a marked hematuria reduction following LDL-A in lupus nephritis. LDL-A is a valuable adjunctive treatment in patients with refractory nephrotic syndrome or highly active lupus nephritis unresponsive to conventional induction therapies.

Anti-nephrin autoantibodies in steroid-resistant nephrotic syndrome may inform treatment strategy.

Autoantibodies against the podocyte protein nephrin were recently identified in a pediatric cohort primarily comprising steroid-sensitive (SSNS) and steroid-dependent (SDNS) nephrotic syndrome (NS). However, their prevalence across all NS subtypes, particularly in steroid-resistant nephrotic syndrome (SRNS), and their relation to therapy response remain need to be determined to advance pathophysiological understanding and refine treatment strategies. A multicenter cohort study measuring anti-nephrin autoantibodies in samples from children with SSNS, SDNS, non-genetic and genetic SRNS was conducted. Sixty nine of 101 (68%) patients with SSNS, 19 of 67 (28%) patients with SDNS, 14 of 103 patients (14%) with non-genetic SRNS and one of 62 patients (2%) with genetic SRNS were positive for anti-nephrin autoantibodies. The prevalence of anti-nephrin autoantibodies increased with presence of active disease in cases of SSNS and SDNS. Within the group of non-genetic SRNS patients with active disease, anti-nephrin positivity was found in 13 of 74 (18%) patients responding to intensified immunosuppression compared to none of 17 patients with multidrug-resistant SRNS. The prevalence of anti-nephrin antibodies is substantially higher in children with steroid responsive NS than in those with SRNS, suggesting that anti-nephrin antibodies primarily drive SSNS/SDNS. In contrast, NS due to podocyte gene mutations is primarily genotype-caused. Anti-nephrin autoantibodies may serve as a positive prognostic marker in pediatric NS, indicating a favorable response to immunosuppressive therapy.

Urinary interleukin 13 level in steroid sensitive and resistant nephrotic syndrome: a cross-sectional single center study

Nephrotic syndrome, the most common glomerular disease in pediatric population, is classified into two groups of steroid sensitive (SSNS) and resistant (SSRS). There is growing evidence on the role of T cells cytokines, including interleukin-13, in pathophysiology of nephrotic syndrome and steroid response. This study was a cross-sectional study conducted at Children’s Medical Center Hospital in order to explore the relationship between urinary IL-13 levels and responsiveness to corticosteroid treatment. All children (1 to 15 years) referred from January 2021 to January 2022 diagnosed with nephrotic syndrome were included. Urine samples were collected during the initial phase or relapse of nephrotic syndrome, before the initiation of steroid or alternative treatments. Interleukin-13 levels in the urine were measured using the ELISA method. In this study, 83 cases of nephrotic syndrome were enrolled, of whom 30 (36.1%) were girls and 53 (63.9%) were boys. Out of the 83 cases, 63 (75.9%) were identified as SSNS and 20 (24.1%) as SRNS. There was no significant difference between the urinary interleukin-13 levels between SSNS and SRNS groups (P-value: 0.84). Sex (P-value: 0.598) and age (P-value: 0.704) also had no association with interleukin-13 levels. Further studies in larger population are recommended to better assess the potential of this biomarker to predict response to treatment. .

Subclinical systolic dysfunction in children with steroid-resistant nephrotic syndrome identified by speckle tracking echocardiography.

Steroid resistant nephrotic syndrome (SRNS) is a clinical phenotype of nephrotic syndrome (NS) that does not respond to steroid therapy and usually results in kidney failure. The aim of this study was to determine whether children with SRNS have subclinical left ventricular systolic dysfunction and, if so, to identify the risk factors for myocardial involvement in those children. This prospective case-control study included of 35 children with SRNS, 40 children in the healthy control group, and 40 children with NS during the initial episode as the diseased control group. Conventional echocardiography, tissue Doppler imaging (TDI), and speckle tracking echocardiography (STE) were performed on all the studied children. No statistically significant difference in conventional echocardiography's parameters were detected between the patient and control groups. TDI revealed that the E/E' ratio was significantly greater in the SRNS group than in both the healthy and diseased control groups (P = 0.001). The left ventricle global longitudinal strain (LV GLS) was markedly lower in children with SRNS than in healthy controls and NS patients (the diseased controls) (P = 0.001). Multiple binary regression analysis for the predictors of systolic dysfunction in SRNS patients revealed that the serum albumin is the only variable that predicts systolic dysfunction in these children. Subclinical systolic and diastolic LV dysfunction should be screened in NS especially SRNS children.

Short-term efficacy of rituximab in children with calcineurin inhibitor resistant steroid resistant nephrotic syndrome

Objective: To investigate the short-term efficacy and safety of rituximab (RTX) in children with calcineurin inhibitor (CNI) resistant steroid resistant nephrotic syndrome (SRNS). Methods: A retrospective case analysis was conducted. Thirteen children with CNI resistant SRNS who were regularly treated with RTX (375 mg/m2 per dose (maximum dose 500 mg), 1 dose per week, a total of 4 doses) in Department of Nephrology, Children's Hospital of Fudan University from January 2016 to December 2023 were enrolled. The general data, disease related information, urinary protein/creatinine, serum albumin, blood creatinine before RTX treatment, immunosuppressants, adverse events, and monthly urinary protein/creatinine, serum albumin, and blood creatinine indexes within 6 months after RTX treatment were collected. The changes of urinary protein/creatinine, serum albumin and estimated glomerular filtration rate (eGFR) before and after RTX at 3 and 6 months were analyzed by using paired sample t test and Wilcoxon signed-rank test. Results: Among the 13 patients, 8 were male and 5 were female. The age of disease onset was 4.0 (2.9, 6.8) years and the age of RTX treatment was 9.8 (5.9, 13.6) years. There were 8 cases of focal segmental glomerulosclerosis, 3 cases of minimal change disease and 2 cases of mesangial proliferative glomerulonephritis. No clinically significant gene variation was detected in 12 cases and the other one did not receive gene test. Before RTX treatment, 11 cases were in chronic kidney disease stage G1, and 1 case each was in stage G2 and stage G3. Ten children completed 4 doses of RTX treatment, 1 patient completed 3 doses, and 2 patients completed 2 doses. Urinary protein/creatinine in 13 children at 3 and 6 months after RTX treatment was significantly lower than baseline (0.60 (0.13, 2.04), 0.49 (0.28, 1.10) vs. 1.44 (0.76, 4.11) mg/mg, Z=-2.34, -2.34, both P<0.05), and serum albumin was significantly higher than baseline ((35±8), (34±7) vs. (30±6) g/L, t=2.30, 2.60, both P<0.05). The eGFR at 6 months after RTX treatment was not significantly different from the baseline ((110±32) vs. (113±35) ml/(min·1.73 m2),t=-0.76,P>0.05)). No serious adverse reactions occurred in this study. Conclusion: RTX could reduce urinary protein and increase serum albumin in short-term treatment in children with CNI resistant SRNS without significant side effects.

WCN25-1602 "Epigenetic and Metabolic Regulation: The Role of HDAC2 and AMPK1 in Drug Resistance in Steroid Resistant Nephrotic syndrome"

WCN25-1602 "Epigenetic and Metabolic Regulation: The Role of HDAC2 and AMPK1 in Drug Resistance in Steroid Resistant Nephrotic syndrome"

Case report: Novel ACTN4 variant of uncertain significance in a pediatric case of steroid-resistant nephrotic syndrome requesting kidney transplantation

Case report: Novel ACTN4 variant of uncertain significance in a pediatric case of steroid-resistant nephrotic syndrome requesting kidney transplantation

Past and future in vitro and in vivo approaches toward circulating factors and biomarkers in idiopathic nephrotic syndrome.

Predicting the risks of progression to chronic kidney disease (CKD) stage 5 in idiopathic nephrotic syndrome (NS) and recurrence of the disease (rNS) following kidney transplantation (KT) is a key assessment to provide essential management information. NS has been categorized etiologically as genetic and immune-based. A genetic cause can be identified in ~ 30% of children with steroid-resistant NS (SRNS), a finding associated with a very low risk of rNS following KT. In immune-based NS, clinical overlap is observed among steroid-sensitive NS, secondary-resistant NS, and SRNS not associated with disease-causing genetic variants (non-monogenic SRNS). While ~ 50% of SRNS patients with noidentified monogenic disease respond to intensified immunosuppressive treatments, the ones that do notrespond to this therapy have a high risk of progression to CKD stage 5 and post-KT rNS. Secondary-resistant patients who progress to CKD stage 5 display the highest risk of post-KT rNS. The proposed shared underlying mechanism of the immune-based NS associated with post-KT rNS is based on a systemic circulating factor (CF) that affects glomerular permeability by inducing foot process effacement and focal segmental glomerulosclerosis. However, identifying patients without a detected genetic form who will recur post-KT is a major challenge. Extensive efforts, therefore, have been made to identify CFs and biomarkers potentially capable of predicting the risk of progression to CKD stage 5 and post-KT rNS. This review discusses the in vitro and in vivo approaches employed to date to identify and characterize potential CFs and CF-induced biomarkers of recurrent NS and offers an assessment of their potential to improve outcomes of KT in this patient population.

Steroid-resistant nephrotic syndrome due to renal-limited thrombotic microangiopathy and membranous nephropathy after allogeneic hematopoietic stem cell transplantation successfully treated with calcineurin inhibitors.

Transplantation-associated thrombotic microangiopathy (TMA) is a severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with high mortality. As calcineurin inhibitors (CNIs) reportedly contribute to TMA via drug-induced endothelial injury, treatment of TMA often involves CNI discontinuation or dose reduction. However, renal-limited TMA, defined as biopsy-proven renal TMA without the classical triad (hemolytic anemia, thrombocytopenia, and organ damage), has rarely been reported after allo-HSCT, and its optimal management remains unknown. Herein, we report three cases of renal-limited TMA after allo-HSCT that presented with nephrotic syndrome, in which renal biopsy showed TMA and concurrent membranous nephropathy. All patients were refractory to glucocorticoid monotherapy and the addition of CNIs led to complete remission of nephrotic syndrome. Renal-limited TMA after allo-HSCT may present as nephrotic syndrome with distinct pathophysiological features from renal-limited TMA in non-allo-HSCT recipients. Previous reports have suggested that renal-limited TMA after allo-HSCT is associated with renal graft-versus-host disease, and thus optimizing immunosuppressive therapy, including CNI treatment, may be useful. CNI treatment may be an option even in the presence of renal-limited TMA after allo-HSCT accompanied by concurrent membranous nephropathy.

A rare case of steroid-resistant nephrotic syndrome complicated by Wernicke's encephalopathy.

Wernicke's encephalopathy (WE) is a severe neurological condition caused by the deficiency of thiamine, which is a vitamin B1 molecule. Herein, we present the case of a 3-year-old girl with steroid-resistant nephrotic syndrome (SRNS) who did not achieve remission despite steroid pulse therapy (MPT) and rituximab. She had frequent vomiting and decreased oral intake on the 61st day. High-calorie total parenteral nutrition was initiated on the 86th day, and levothyroxine was administered for suspected hypothyroidism. On the 88th day, she experienced altered consciousness with ocular deviation and abnormal electroencephalography findings, raising suspicion of WE. Following thiamine supplementation, recurrence of symptoms and neurological sequelae were not observed. Following 10 courses of MPT, rituximab, and mycophenolate mofetil, the patient achieved incomplete remission from SRNS. Monitoring levels of water-soluble vitamins in prolonged cases of nephrotic syndrome, such as SRNS, is critical to prevent WE and irreversible neurological damage.

Genetic and clinical spectrum of steroid-resistant nephrotic syndrome with nuclear pore gene mutation.

Steroid-resistant nephrotic syndrome (SRNS) is insensitive to steroid therapy and overwhelmingly progresses to kidney failure (KF), the known pathogenic genes of which include key subunits of the nuclear pore complex (NPC), a less-recognized contributor to glomerular podocyte injury. After analyzing their clinical characterizations and obtaining parental consent, whole-exome sequencing (WES) was performed on patientswith SRNS. Several nucleoporin (NUP) biallelic pathogenic variants were identified and further analyzed by cDNA-PCR sequencing from white cells of peripheral blood, minigene assay, immunohistochemical (IHC) staining, and electron microscopy (EM) ultrastructure observation of kidney biopsy, as well as multiple in silico prediction tools, including 3D protein modeling. Here, in six familieswith SRNS, we identified pathogenic mutations in NUP85/93/107/160 genes. Specifically, thepatient with NUP93mutation developed KF six months after diagnosis at 1year 2months. Two missense mutations, c.1655A > G and c.1604A > C, disrupted the protein stability of NUP93 by IHC staining of kidney biopsy. Ultrastructurally, the above mutations led to severe vacuolization and deformed nucleus in podocytes, torn and dissolved glomerular basement membrane, and diffuse foot process effacement. Thepatient with NUP85mutation reached chronic kidney disease (CKD)stage 3 after 4years follow-up, with exons 2-5 in-frame loss and a missense variant at c.511C > T, not affecting NUP85 expression but possibly weakened interaction with Seh1. Additionally, an extended endoplasmic reticulum (ER) tubule was readily observed under EM. Meanwhile, dilated ER was also found in twochildren with NUP160mutations (c.3330 delA and c.2407 G > A; c.2241 + 1 (IVS17) G > T and c.3656T > G), one of which has undergone kidney transplantation. Compound heterozygous variants in NUP107, c.1695 G > C and c.1360 C > T, were found in a 14-year-old girl initially diagnosed with CKDstage5, with the former variant causing exon 19 skipping and early translation termination. c.1311 + 1(IVS15) G > A and c.1790 C > T were identified in the second affected girl, with the former causing exon 15 skipping and an in-frame loss of aa417-438, which disrupted the stability of NUP107 and interaction with NUP133. Our findings expand the spectrum of phenotypes and genotypes of NUPs-associated SRNS and suggest its possible pathogenic mechanism in nuclear and ER homeostasis.

Clinical follow-up of 2 families with glomerulopathy caused by COQ8B gene variants and literature review.

Primary coenzyme Q10 (CoQ10) deficiency is an autosomal recessive genetic disease caused by mitochondrial dysfunction. Variants in Coenzyme Q8B (COQ8B) can cause primary CoQ10 deficiency. COQ8B-related glomerulopathy is a recently recognized glomerular disease that most often presents as steroid-resistant nephrotic syndrome (SRNS) in childhood. The disease often progresses to kidney failure and the renal histopathology is most commonly focal segmental glomerulosclerosis (FSGS). Four SRNS cases (2 females and 2 males) from 2 unrelated families who were followed clinically for nearly 3 years. Clinical exome testing and analyses were performed by MyGenostics Laboratory in China to evaluate unexplained proteinuria given the strong family history of glomerular disease and histologic evidence of SRNS. Pathogenic variants were identified in COQ8B in the exome studies and confirmed by direct sequencing. Clinical exome sequencing revealed biallelic variants of the COQ8B gene in 2 families. In the Family 1, the oldest of three affected siblings died of renal failure at 11 years of age. Based on the results of genetic testing which identified a homozygous variant of COQ8B, the other two affected siblings with mild proteinuria and normal renal function were treated with CoQ10 oral supplementation at an early stage. Coenzyme Q10 treatment was effective in reducing proteinuria levels in both patients from Family 1 over the first 6 months and the two patients still have low-level proteinuria and normal renal function at nearly three years. In Family 2, clinical exome sequencing revealed a compoundheterozygous variants of COQ8B in a patient with biopsy- proven FSGS. His disease was unresponsive to prior treatment with glucocorticoids and cyclosporine. Oral CoQ10 was initiated based on his genetic diagnosis and was it was effective in reducing proteinuria over the first 5 months months of therapy. However after 1 year, his disease progressed tokidney failure. Kidney transplantation was performed at 5 years of age and his condition has been stable without rejection and no recurrence of disease. COQ8B gene variant-related glomerulopathy often presents as SRNS without obvious extrarenal manifestations. The histopathology is mainly FSGS and follows an autosomal recessive mode of inheritance. Some patients may benefit from early coenzyme Q10 supplementation. For patients whose disease progresses to kidney failure, kidney transplantation can be an effective treatment. For children with unexplained proteinuria and abnormal renal function, genetic testing should be performed early in the course of disease to guide therapy where possible and improve prognosis.

Steroid-resistant nephrotic syndrome as paraneoplastic syndrome of Waldenström macroglobulinemia: a case report.

Reports of glomerulonephritis associated with lymphoproliferative disorders are common, but reports of minimal change disease (MCD) accompanying non-Hodgkin's lymphoma are rare. Here, we present a case of a 45-year-old woman diagnosed with primary Waldenström's macroglobulinemia (WM) during MCD treatment. Her kidney biopsy revealed endothelial cell injury in parts of the MCD. Subsequently, she developed steroid-resistant nephrotic syndrome and temporary acute kidney injury, requiring dialysis. Remission of the nephrotic syndrome was achieved after initiating combination therapy with bendamustine and rituximab for WM. The renal histological findings and treatment course suggest a causal relationship between MCD and WM in this case. The pathogenesis of MCD associated with WM may involve the release of glomerular permeability factors derived from B lymphocytes. Although mild WM is often managed with observation, steroid-resistant nephrotic syndrome associated with WM should raise suspicion of a paraneoplastic syndrome, necessitating active chemotherapy targeting WM as a critical treatment approach.

Single-cell transcriptomics in a child with coenzyme Q10 nephropathy: potential of single-cell RNA sequencing in pediatric kidney disease.

Coenzyme Q10 (CoQ10) nephropathy is a well-known cause of hereditary steroid-resistant nephrotic syndrome, primarily impacting podocytes. This study aimed to elucidate variations in individual cell-level gene expression in CoQ10 nephropathy using single-cell transcriptomics. We conducted single-cell sequencing of a kidney biopsy specimen from a 5-year-old boy diagnosed with a CoQ10 nephropathy caused by a compound heterozygous COQ2 mutation complicated with immune complex-mediated glomerulonephritis. The analysis focused on the proportion of cell types, differentially expressed genes in each cell type, and changes in gene expression related to mitochondrial function and oxidative phosphorylation (OXPHOS). Our findings revealed a uniform downregulation of mitochondrial gene expression across various cell types in the context of these mutations. Notably, there was a specific decrease in mitochondrial gene expression across all cell types. The study also highlighted an altered immune cell population proportion attributed to the COQ2 gene mutation. Pathway analysis indicated a downregulation in OXPHOS and an upregulation of various synthesis pathways, particularly in podocytes. This study improves our understanding of CoQ10 nephropathy's pathogenesis and highlights the potential applications of single-cell sequencing in pediatric hereditary kidney diseases.

Determinants of Acute Kidney Injury in Children With Nephrotic Syndrome: A Prospective Observational Study.

Background Nephrotic syndrome (NS) is a common renal ailment among children, typically manifesting as a relapsing-remitting pattern. Most of the cases are managed on an outpatient basis, but a subset of patients experience complications, e.g., acute kidney injury (AKI). Although historically more prevalent in secondary NS, AKI is now occurring increasingly in children with idiopathic NS. However, the literature on AKI in this population consists of case reports and retrospective studies, particularly from India, so the study was planned to identify various risk factors that precipitate AKI in a child with NS. The secondary objective was to assess the hydration status of children having NS and its association with the development of AKI. Materials and methods This longitudinal study was conducted in the Department of Pediatrics at the All India Institute of Medical Sciences, Raipur, Chhattisgarh, from October 2021 to April 2023. Children of both genders and age groups between three months and 15 years, satisfying the International Society for Pediatric Neurosurgery 2021 guideline for the diagnosis of NS, were included in the study. Children having chronic kidney disease were excluded. Using the non-probability convenient sampling technique, 57 patients with NS were enrolled in the study. The patients without AKI were evaluated daily for the development of AKI using the Kidney Disease Improving Global Outcomes 2012 guideline until day 14 or discharge and followed up for six months. Records of those children who were admitted with AKI were reviewed for possible risk factors of AKI. Data was analyzed on Epi Info software enUS version 7.3.2 (Centers for Disease Control and Prevention, Atlanta, GA, USA). Categorical data were expressed as a percentage and/or 95% confidence interval (CI) of the estimate and compared using Chi-square or Fisher's exact test. A p-value ≤0.05 was considered statistically significant. The odds ratio (OR) for risk factors for AKI was determined using logistic regression. Results The mean age of the study subjects at the onset of the disease was 5.34 ± 3.66 years. The common presentations were edema (94.74%) and oliguria (80.7%). The majority (89.2%) showed a response to steroid therapy. About 56.14% of children developed AKI, and stages 2 and 3 AKI were more common, 37.5% each. About 53.12% and 46.88% of children developed pre-renal AKI and intrinsic AKI, respectively; 45.61% had hypertension at admission, with the majority having stage 1 hypertension (38.46%). Only six (10.5%) children had sickle cell trait, and all developed AKI during follow-up. Forty-two (73.68%) children had nephrotoxic drug exposure, with the most common drug being enalapril, followed by nephrotoxic antibiotics. Out of 10 children with AKI who underwent renal biopsy, focal segmental glomerulosclerosis was the most common entity (60%). The notable parameters that were found to have statistical significance for AKI were low eGFR at admission, hypertension, nephrotoxic drug exposure, inadequate water intake, fractional excretion of sodium (FeNa), and urine potassium index as markers of renal hypoperfusion, infections, steroid-resistant nephrotic syndrome, and significant glomerular lesions. Conclusion The present study demonstrates an association between traditional risk factors and the causation of AKI. However, high urine osmolality, raised urine K+ index, and FeNa suggestive of raised aldosterone levels had a significant association with AKI.

Cardiac function evaluation in children with primary nephrotic syndrome

Background Pediatrics with nephrotic syndrome (NS) have an increased prevalence of cardiac difficulties. Several risk factors enhance the increase of cardiac modification such as elevation of blood pressure, cholesterol level, increased BMI, inflammation, prolonged treatment with steroids and other drugs that suppress the immunity, hypercoagulability state, and stress. Aim The aim of this work was to evaluate cardiac function in children with primary NS using echocardiography. Patients and methods This case–control study was conducted on 60 children. They were subdivided into three groups: group Ι; 20 cases steroid sensitive NS. Group II 20 cases with steroid resistant NS. Group ΙΙΙ; 20 healthy children with matched age and sex as controls. All patients undergo medical history taking, clinical examination, and investigations: laboratory investigations (complete blood count, complete urine analysis, 24-h urine collection for proteinuria and urine volume, blood urea, and serum creatinine, total and ionized calcium level, serum proteins and albumin, total serum cholesterol, liver enzymes; alanine aminotransferase, aspartate aminotransferase, erythrocyte sedimentation rate, antinuclear antibody and Complement C3 and C4). Radiological investigations (plain chest radiography, ECG, and echocardiographic examination (M Mode echocardiography, two-dimensional echocardiography). Results There was a significant increase in left ventricular mass and left ventricular mass index in the nephrotic children. Conclusion Echocardiography provides a widespread evaluation of cardiac functions.

Changes in Serum Immunoglobulin Levels Play as Predictors of Treatment Response and Prognosis in Pediatric Idiopathic Nephrotic Syndrome During the Remission Phase.

Nephrotic syndrome is an immune-mediated renal disorder characterized by T-cell and B-cell dysfunctions with changes in immunoglobulin (Ig) levels and the IgG:IgM ratio. Therefore, this study aimed to determine whether the serum level of Igs can be considered as an index to predict the response to treatment and the prognosis of idiopathic nephrotic syndrome (INS) in children in the remission phase. The study population consisted of 38 children with INS in the remission phase and 38 age- and sex-matched healthy children. Blood samples were collected from participants and serum values of IgG, IgM, IgE, and IgA were measured using EISA KITS from Aptech Services. The IgG:IgM ratio was studied in the participants. Patients significantly increased IgM and IgE levels compared with healthy subjects, unlike IgG and IgA values (p < 0.001-0.05). Patients with steroid-resistant nephrotic syndrome (SRNS) had a significant increase in IgM levels compared with those with steroid-sensitive nephrotic syndrome (SSNS) (p < 0.05). While, subjects with SRNS showed significant reductions in IgG and IgA values (p < 0.01). There were significant differences in the levels of IgG and IgM between steroid-sensitive patients with and without a history of relapse (p < 0.01). Furthermore, patients with steroid-independent and frequently relapsing NS showed a significant increase in IgE value compared with that of subjects with steroid-dependent and relapse (p < 0.05). The ratio of IgG/IgM was significantly reduced in patients compared with healthy individuals (p < 0.05). Other results indicated that there was a significant difference between patients with steroid-independent and steroid-dependent who had a history of relapse (p < 0.01). Alterations in serum Ig values can be considered as predictors of treatment response and prognosis in pediatric idiopathic nephrotic syndrome during the remission phase.

The association of steroid-resistant nephrotic syndrome with non-autoimmune thyroid in children

The association of steroid-resistant nephrotic syndrome with non-autoimmune thyroid in children

Childhood idiopathic nephrotic syndrome: recent advancements shaping future guidelines.

Childhood idiopathic nephrotic syndrome is an important pediatric kidney disease associated with significant morbidities and even mortality. Several guidelines have been developed to standardize the terminology and patient care among the pediatric nephrology community. Since the publication of these guidelines, there have been major breakthroughs in the disease management and the understanding of underlying pathogenesis through multi-omics investigations, including the identification of anti-nephrin autoantibodies, genetic susceptibility loci, and the pathogenic role of B cell subsets. In this educational review, we summarize the recent major advancements in idiopathic nephrotic syndrome and attempt to provide potential therapeutic approaches in both steroid-sensitive and steroid-resistant nephrotic syndrome that may shape future guideline development.

PDSS1 mutations-associated steroid-resistant nephrotic syndrome: case report and review of literature.

PDSS1 mutations hamper Coenzyme Q10 biosynthesis and cause a rare multisystem mitochondrial disease characterized by diverse clinical features and limited treatment options. To date, renal involvement has been reported in only one patient. We report a new female patient with compound heterozygous PDSS1 mutations and the clinical outcome following a trial of Coenzyme Q10 therapy. Our patient presented with developmental delay and regression at age three, which progressed to steroid-resistant nephrotic syndrome at age six, leading to stage 5 chronic kidney disease. Whole exome sequencing identified two pathogenic variants in the PDSS1 gene. High doses of Coenzyme Q10 therapy had no effect at this advanced stage of disease. Coenzyme Q10 treatment did not appear to improve the clinical outcome in this patient. Further data is needed to better understand the phenotypic spectrum of PDSS1-associated disruption, and the potential benefit of early Coenzyme Q10 therapy.