RARE DISEASE
Idiopathic nephrotic syndrome
Idiopathic nephrotic syndrome
Idiopathic nephrotic syndrome
Drug discovery
2
drugs
With orphan designations
Overview
Idiopathic nephrotic syndrome (INS) is a glomerular disorder characterized by nephrotic-range proteinuria (≥3.5 g/day), hypoalbuminemia, edema, and hyperlipidemia. It is the most common childhood glomerular disease, primarily caused by minimal change disease (MCD) in children and membranous nephropathy or focal segmental glomerulosclerosis (FSGS) in adults. INS often follows a relapsing-remitting course, requiring long-term immunosuppression and supportive care to manage complications like infections, thrombosis, and chronic kidney disease [1][5][12].
Population
Children: Peak onset at 2–6 years; incidence of 2–7/100,000/year, with higher rates in Asian (up to 7.1/100,000) and Black (3.5/100,000) populations compared to Caucasians (1.8/100,000) [2][12][17].
Adults: Annual incidence of ~3/100,000; FSGS predominates in Black adults, membranous nephropathy in White adults [1][4][7].
Sex: Pediatric cases show a 2:1 male-to-female ratio; no gender predominance in adults [7][12].
Burden
Clinical: High relapse rates (60–80% in children), thromboembolic risk (8–17%), and progression to CKD/ESRD in steroid-resistant cases [4][6][16].
Economic: Annual direct costs exceed $3,000 per patient; caregivers spend >170 hours/year managing dietary and medical needs [4][9].
Psychosocial: 15–20% of caregivers report significant psychological distress due to caregiving demands [9][18].
Therapies
First-line: Corticosteroids (e.g., prednisone) induce remission in 80–90% of pediatric MCD cases [3][14].
Adjunctive: ACE inhibitors/angiotensin receptor blockers reduce proteinuria; diuretics manage edema [1][5][8].
Steroid-resistant/dependent cases: Immunosuppressants (cyclophosphamide, calcineurin inhibitors, rituximab) or alkylating agents for frequent relapses [3][13][16].
Categories: rare renal diseases, rare transplant-related disorders
Research Papers
1,611 drug discovery papers about Idiopathic nephrotic syndrome, with 5 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,611 drug discovery papers about Idiopathic nephrotic syndrome, with 5 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-24 | [The value of immuno-histochemical analysis of renal glucocorticoid receptor expression in idiopathic nephrotic syndrome].
The response to corticosteroid therapy in idiopathic nephrotic syndrome (INS) is variable. Glucocorticoid receptors (GR), which are essential for steroid action, may partly explain this variability. To investigate the relationship between podocyte glucocorticoid receptor expression assessed by immunohistochemistry and the response to corticosteroid therapy in INS. This was a retrospective study conducted over a 22-year period, including 29 patients with minimal change disease or primary focal segmental glomerulosclerosis. Podocyte GR expression was evaluated by immunohistochemistry and correlated with treatment response. In total, 18 patients were steroid-sensitive, 6 were steroid-dependent, and 5 were steroid-resistant. No conventional clinical, laboratory, or histological factor was predictive. However, GR expression was higher in steroid-sensitive than in steroid-resistant patients (p = 0.046). Podocyte glucocorticoid receptor expression may predict the response to corticosteroid therapy in idiopathic nephrotic syndrome.
2026-09-22 | Thromboembolic prophylaxis in childhood idiopathic nephrotic syndrome. From pathophysiology to clinical management
Thromboembolic complications remain among the most serious complications of childhood idiopathic nephrotic syndrome (INS). Although their incidence is considerably lower than in adults, venous thromboembolism continues to cause substantial morbidity and occasional mortality, including pulmonary embolism, cerebral venous sinus thrombosis, and extensive deep venous thrombosis. Preventive management remains controversial because most affected children may not develop thrombosis, whereas pharmacological prophylaxis exposes many low-risk patients to potential overtreatment. Current recommendations are largely based on retrospective studies, expert opinions, and extrapolation from adult nephrotic syndrome, while prospective pediatric evidence remains scarce. This review examines the contemporary understanding of thrombogenesis in childhood INS, emphasizing that hypercoagulability extends beyond urinary antithrombin loss to involve hepatic overproduction of procoagulant factors, impaired fibrinolysis, platelet activation, endothelial dysfunction, and hemoconcentration. We also discuss the possibility that historical thrombotic risk may have been amplified by prolonged corticosteroid exposure and consider whether the widespread adoption of steroid-sparing immunosuppressive therapies and earlier relapse detection may have modified the epidemiology of thromboembolism in the modern therapeutic era. Current preventive strategies—including no routine prophylaxis, biomarker-guided individualized approaches, aspirin, and prophylactic low-molecular-weight heparin (LMWH)—are critically reviewed. We argue that increasingly complex biomarker-based algorithms have not demonstrated clear clinical superiority over simple, pragmatic decision-making. Severe hypoalbuminemia provides a pragmatic surrogate of nephrotic severity and may therefore help identify children in whom the overall prothrombotic state is likely to be substantial. We are not proposing albumin <20 g/L as a validated predictor of thrombosis. We are proposing it as a pragmatic clinical trigger for considering prophylaxis in a disease in which no validated predictive model currently exists. We propose a pragmatic risk-stratified approach in which routine pharmacological prophylaxis is unnecessary for early biochemical relapses with minimal clinical manifestations but should be strongly considered in children and adolescents with clinically significant active nephrotic syndrome associated with severe hypoalbuminemia (approximately <20 g/L), provided no major contraindications exist. Where feasible, LMWH appears to be the most appropriate prophylactic agent. Until prospective pediatric studies better define thrombotic risk and validate prediction models, practical consistency based on clinically meaningful risk thresholds may provide a more rational framework than theoretical precision for thromboprophylaxis in childhood INS.
2026-09-03 | Efficacy and safety of 5-day versus 7-day antibiotic therapy for spontaneous bacterial peritonitis in children with idiopathic nephrotic syndrome: an open-label randomized controlled trial.
Spontaneous bacterial peritonitis (SBP) is a life-threatening complication of idiopathic nephrotic syndrome (INS) in children. Evidence on the optimal duration of antibiotics in this population is limited. We investigated whether 5-day antibiotic therapy is non-inferior to 7-day therapy for SBP in children with INS. In this single-center, open-label, randomized controlled non-inferiority trial, 50 children aged 1-14 years with INS and SBP were allocated 1:1 to intravenous ceftriaxone for 5 days (Group A, n = 25) or 7 days (Group B, n = 25). The primary outcome was composite clinical response (resolution of fever, abdominal pain, and tenderness) at the end of treatment, analyzed by intention-to-treat. The pre-specified non-inferiority margin was -15%. Secondary outcomes included bacteriological cure, cytological response, and the need for additional antibiotics. Fifty children [median age 50 (30.8-92) months] were randomized. Composite clinical response was achieved in 25/25 (100%) in Group A versus 22/25 (88%) in Group B (risk difference 12%, 95% CI -3.5% to 30.0%; P = 0.23); the lower CI bound exceeded the -15% non-inferiority margin, establishing non-inferiority. Bacteriological cure was achieved in 96% of both groups. Cytological response (64% vs 72%; P = 0.54) was inconclusive for non-inferiority. Additional or modified antibiotic therapy was required in 16% versus 20% (P = 1.00). Median hospitalization was comparable (10 vs 11 days; P > 0.05). No ceftriaxone-related adverse events were recorded. Five-day intravenous ceftriaxone is non-inferior to 7-day therapy for SBP in children with INS, with respect to composite clinical response; the secondary outcome of cytological response was inconclusive for non-inferiority.
2026-07-27 | Paraneoplastic Minimal Change Disease Signaling Post-Transplant AML Relapse: Two Cases and a Literature Review.
Membranous nephropathy (MN) and minimal change disease (MCD) are the most common causes of nephrotic syndrome following hematopoietic stem cell transplantation (HSCT), a complication conventionally attributed to chronic graft-versus-host disease (GVHD). Paraneoplastic MCD is well described in lymphoid malignancies but is rarely reported in myeloid neoplasms. We report two cases of biopsy-confirmed MCD presenting as the initial manifestation of acute myeloid leukemia (AML) relapse following allogeneic HSCT. Both patients were White men in their sixties with relapsed/refractory AML who developed nephrotic-range proteinuria and acute kidney injury after matched unrelated donor HSCT without histologic evidence of GVHD. Renal biopsies confirmed MCD in both cases. Corticosteroid therapy was ineffective in halting renal deterioration; renal function improved only after initiation of leukemia-directed therapy, with one patient achieving dialysis independence. These cases highlight a rare paraneoplastic presentation of AML relapse. Nephrotic syndrome due to MCD may signal post-HSCT leukemia recurrence, and evaluation for AML relapse warrants consideration in steroid-refractory cases or those without concurrent GVHD. In such cases, control of the underlying malignancy, rather than escalation of immunosuppression, may be central to renal recovery.
2026-07-12 | Cerebral venous sinus thrombosis secondary to relapsed minimal change disease: a case managed with endovascular thrombolysis.
Cerebral venous sinus thrombosis (CVST) is a rare type of stroke characterized by the formation of blood clots within the dural venous sinuses which has a high mortality rate. Despite its potential severity, cerebral venous sinus thrombosis secondary to nephrotic syndrome remains rarely reported and under-recognized in clinical practice. We described a 20-year-old male who presented with a relapse of minimal change disease, complicated by extensive CVST. On the basis of anticoagulant therapy, his neurological condition deteriorated rapidly, manifesting as altered mental consciousness, progressive limb weakness, and new-onset seizures. Given the failure of conventional medical management, endovascular therapy of catheter-directed thrombolysis was performed. The patient's neurological status improved dramatically within days. This case demonstrates that cerebral venous sinus thrombosis should be considered in nephrotic syndrome patients presenting with even subtle or non-specific neurological symptoms. Patients with focal neurological deficits, altered mental status, new-onset seizures, or unusual headache should undergo prompt neurological evaluation and appropriate brain imaging, including computed tomography venography (CTV) or magnetic resonance venography (MRV) when CVST is suspected. In the specific setting of nephrotic syndrome, clinicians should maintain a heightened index of suspicion for CVST, even when initial neurological findings are subtle or non-specific. As illustrated by this case, early recognition and timely escalation to endovascular therapy can be life-saving when conventional anticoagulation fails to prevent neurological deterioration. Our patient achieved complete neurological recovery and sustained remission of nephrotic syndrome, underscoring the value of multidisciplinary collaboration and individualized treatment strategies.
proteins
2026-09-23 | Comparison of Albumin versus Fresh Frozen Plasma in the Treatment of Children with Diuretic-Resistant Oedema in Idiopathic Nephrotic Syndrome at a Tertiary Hospital
Comparison of Albumin versus Fresh Frozen Plasma in the Treatment of Children with Diuretic-Resistant Oedema in Idiopathic Nephrotic Syndrome at a Tertiary Hospital
2026-06-19 | IgM Hyposialylation Modulates Podocyte Vulnerability in Patients With Idiopathic Nephrotic Syndrome.
Altered Ig glycosylation has been implicated in antibody-mediated podocytopathies; however, the functional relevance of IgM sialylation remains poorly defined. Previous evidence suggests that circulating cationic or hyposialylated IgM may contribute to podocyte vulnerability in idiopathic nephrotic syndrome (iNS). Serum IgM from 86 pediatric and adult patients with podocytopathies, 20 patients with membranous nephropathy (MN), 20 patients with lupus nephritis (LN), and 30 healthy controls were analyzed by lectin-based enzyme-linked immunosorbent assay (ELISA) using biotinylated lectins to assess terminal N-glycan residues, including Sambucus nigra agglutinin (SNA) and Ricinus communis agglutinin I (RCA-I). Serum levels of the sialyltransferase ST6GAL1 and the sialidases neuraminidase-1 (NEU1) and neuraminidase-3 (NEU3) were quantified. Cultured human podocytes were exposed to native, desialylated, or resialylated IgM and analyzed by confocal microscopy, quantitative proteomics, phosphoproteomics, and metabolic assays. IgM from patients with iNS showed reduced SNA binding, which inversely correlated with proteinuria and circulating NEU1/NEU3 levels. In paired samples, SNA reactivity decreased during relapse and increased during remission. ST6GAL1 was undetectable across all groups, whereas phospholipase A2 receptor 1(PLA2R1)-positive MN displayed reduced RCA-I binding. Podocytes exposed to hyposialylated or desialylated IgM exhibited disorganization of the actin cytoskeleton, reduced nephrin signal, increased lipid peroxidation, and decreased ATP levels. Resialylated IgM displayed podocyte morphological and metabolic features not statistically distinguishable from those observed under control conditions. Proteomic and phosphoproteomic analyses highlighted modulation of mitogen-activated protein kinase (MAPK)-, mechanistic Target of Rapamycin (mTOR-), adenosine monophosphate-activated protein kinase (AMPK), and cytoskeleton-related pathways. IgM sialylation status tracks disease activity and modulates podocyte structural, metabolic, and signaling responses, supporting immune glycan remodeling as a disease-associated modifier of podocyte vulnerability in iNS.
2026-01-10 | Celiac Disease in Children with Idiopathic Nephrotic Syndrome-A Retrospective Cohort Study.
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.
2026-01-01 | Coexistence of idiopathic nephrotic syndrome, celiac disease, and dermatitis herpetiformis: a rare paediatric case report
Idiopathic nephrotic syndrome (INS) is the most common cause of nephrotic syndrome in childhood.Celiac disease is an autoimmune gluten-dependent enteropathy, and dermatitis herpetiformis (Duhring's disease) represents its most frequent extraintestinal manifestation.The coexistence of INS, celiac disease, and dermatitis herpetiformis constitutes an exceptionally rare clinical finding.We present the case of a 13-year-old girl diagnosed with all three conditions.Following the introduction of a gluten-free diet, complete remission of both nephrological and dermatological symptoms was achieved.This case highlights the importance of an interdisciplinary diagnostic and therapeutic approach and the need to consider gluten-related disorders in children with INS of atypical presentation.
2025-11-05 | IgM hyposialylation drives podocyte injury in pediatric and young adult patients with podocytopathies
Abstract Introduction Altered immunoglobulin glycosylation has been implicated in antibody-mediated podocytopathies, yet the functional impact of IgM sialylation remains unclear. Previous evidence suggested that circulating cationic or hyposialylated IgM may contribute to podocyte injury in idiopathic nephrotic syndrome (iNS). Methods Serum IgM from pediatric and young adult patients with podocytopathies, membranous nephropathy (MN), lupus nephritis (LN), and healthy controls were analyzed by lectin-based ELISA using a panel of six biotinylated lectins to detect terminal N-glycan residues. Among these, Sambucus nigra agglutinin (SNA) binds α2,6-linked sialic acid, and Ricinus communis agglutinin I (RCA-I) recognizes β1,4-linked galactose. Serum levels of the α2,6-sialyltransferase ST6GAL1 and the sialidases neuraminidase-1 (NEU1) and neuraminidase-3 (NEU3) were quantified. Cultured human podocytes were exposed to patient-derived, control, or enzymatically modified IgM (desialylated/resialylated) and analyzed by confocal microscopy, quantitative proteomics, phosphoproteomics, and metabolic assays. Results IgM from patients with podocytopathies showed reduced SNA binding, which inversely correlated with proteinuria (r = −0.69, P < 0.0001) and with serum sialidases NEU1/NEU3 (r = −0.67/−0.59, P < 0.0001). In paired samples, SNA reactivity decreased during relapse and normalized in remission, indicating dynamic modulation with disease activity. ST6GAL1 was undetectable in all groups. In contrast, PLA2R1-positive MN, in which pathogenic antibodies target podocyte PLA2R1, displayed reduced RCA-I binding. Podocytes exposed to hyposialylated or desialylated IgM exhibited actin disorganization, loss of nephrin signal, increased lipid peroxidation, and decreased ATP synthesis. In contrast, resialylated IgM preserved morphology and metabolism comparable to controls. Proteomic and phosphoproteomic profiling revealed enrichment of MAPK, mTOR, AMPK, and cytoskeletal remodeling pathways. Conclusions IgM hyposialylation, driven by extracellular sialidases up-regulation, correlates with disease activity and promotes oxidative stress, mitochondrial dysfunction, and cytoskeletal remodeling in podocytes, identifying immune glycan remodeling as a modifiable determinant of podocyte injury and a potential biomarker of disease activity. Translational Statement Altered glycosylation of circulating immunoglobulins is emerging as a key mechanism underlying glomerular injury. Here, we demonstrate that hyposialylated IgM, resulting from elevated serum sialidases NEU1 and NEU3, directly induces podocyte cytoskeletal disorganization, oxidative stress, and metabolic impairment. In contrast, enzymatic resialylation maintains podocyte morphology and function at levels indistinguishable from controls, indicating that sialic acid loss is a modifiable determinant of podocyte injury. Clinically, reduced IgM sialylation correlates with proteinuria and disease activity in idiopathic nephrotic syndrome, supporting its potential as a biomarker of relapse and remission. Targeting the sialidase–sialic acid pathway may therefore represent a promising strategy to preserve podocyte integrity and improve outcomes in antibody-negative podocytopathies.
antibodies
2026-09-27 | Long-term outcomes of childhood nephrotic syndrome.
Idiopathic nephrotic syndrome (INS) is the most common chronic glomerular disease in children. Corticosteroids remain first-line therapy, and the initial response, differentiating steroid-sensitive (SSNS) from steroid-resistant (SRNS) forms, is the strongest prognostic factor. While most childhood-onset INS results from an incompletely defined dysregulation of the immune system, up to one-third of children with initial SRNS have a monogenic etiology. SSNS typically follows a relapsing-remitting course, with one-half of the patients having frequent relapses or steroid-dependence (FRNS/SDNS). Although earlier studies suggested that most SSNS patients achieve sustained remission by puberty, approximately one-fourth experience at least one relapse in adulthood. Key predictors of persistent relapsing disease include FRNS/SDNS in childhood and the need for second-line immunosuppression. The disease may evolve into secondary steroid-resistance in <10% patients with SSNS. Kidney failure and death remain uncommon. In contrast, SRNS is associated with higher risks of therapy-and disease-related complications, including growth impairment, obesity, hypertension and cardiovascular risk, osteoporosis, cataracts, calcineurin inhibitor-induced nephrotoxicity, acute kidney injury and progressive chronic kidney disease. The risk of kidney failure is three- to fourfold higher in patients with monogenic and/or multidrug-resistant SRNS. This review synthesizes current evidence on the long-term outcomes of childhood-onset INS, highlights risk stratification across clinical phenotypes, genetic diagnosis and treatment response, and challenges during transition to adult care.
2026-09-24 | Recent key advances in the understanding of the pathogenesis of childhood minimal change disease.
Minimal change disease (MCD) is the leading cause of idiopathic nephrotic syndrome in children, accounting for >85% of cases in those aged 1-12 years. Although 80%-90% of patients achieve initial remission with glucocorticoids, steroid dependence or frequent relapses occur in 55%-60% of cases, necessitating prolonged immunosuppression. Long-term steroid exposure in children is associated with severe age-specific adverse events, including growth retardation, skeletal dysplasia, cataracts, and impaired vaccine responses from immunosuppression. Steroid resistance and chronic kidney disease may also develop in some patients. Recent clinical evidence and literature (2015-2025) have transformed our understanding of MCD from the traditional "single T cell-driven" hypothesis to a multidimensional interactive regulatory network. This network is based on coordinated T- and B-cell dysregulation, mediated by defined podocyte injury pathways and modulated by genetic and environmental factors. Distinct pediatric traits stem from immature immune system development and pediatric podocyte plasticity. In this review, we synthesize recent advances in these pediatric pathogenic mechanisms, delineate age-dependent differences between childhood and adult MCD, and propose a precision medicine framework for disease subtyping, noninvasive biomarker development, and targeted therapies. This work addresses critical unmet clinical needs in the long-term management of pediatric MCD.
2026-09-03 | Outcome of children treated with rituximab for steroid-resistant nephrotic syndrome: Renal histopathology as a response marker.
Steroid-resistant nephrotic syndrome (SRNS) in children remains a major therapeutic challenge. Although calcineurin inhibitors (CNIs) are commonly used as first-line therapy, a substantial proportion of patients fail to achieve remission, and prolonged use may result in nephrotoxicity. Rituximab has emerged as a potential therapeutic option for refractory SRNS; however, treatment responses appear variable, and the influence of underlying renal histopathology remains incompletely understood. The objective of the study was to evaluate the association between renal histopathological findings and clinical response to rituximab in children with CNI-resistant SRNS. Study design and setting: This prospective observational study was conducted between 2011 and 2020 at a university-affiliated tertiary pediatric nephrology center. The study aimed to evaluate the efficacy of rituximab in children with CNI-resistant SRNS and to examine the association between renal histopathological findings and treatment response. Twenty-four children aged 2-12 years were enrolled. Follow-up: Patients were followed prospectively after completion of rituximab therapy through regular clinical and laboratory assessments. The mean follow-up duration after the last rituximab infusion was 5.1 years (range: 6 months-8 years). treatment response definitions: Complete remission was defined according to International Pediatric Nephrology Association recommendations as a urine protein-to-creatinine ratio (UPCR) ≤20 mg/mmol (≤0.2 mg/mg) or negative/trace proteinuria on dipstick testing on at least three consecutive occasions. Partial remission was defined as a UPCR >20 mg/mmol but <200 mg/mmol together with serum albumin ≥30 g/L. No response was defined as failure to achieve either complete or partial remission. Genetic evaluation: Genetic testing was performed in all patients with focal segmental glomerulosclerosis (FSGS), classic minimal change disease (MCD), and MCD with immunoglobulin M (IgM) deposition. No pathogenic or likely pathogenic variants associated with monogenic SRNS were identified in the tested patients. Genetic testing was not performed in patients with IgA nephropathy, membranous nephropathy, C1q nephropathy, or dense deposit disease (DDD). Twenty-four children with SRNS were included (13 males and 11 females; age range 2-12 years). Histopathological diagnoses included FSGS in nine patients (37.5%), MCD in 4 (16.7%), MCD with IgM deposition in 6 (25.0%), DDD in 2 (8.3%), membranous nephropathy in 1 (4.2%), IgA nephropathy in 1 (4.2%), and C1q nephropathy in 1 (4.2%). Overall, 10 patients (41.7%) achieved complete remission and 3 (12.5%) achieved partial remission, predominantly among patients with MCD and MCD with IgM deposition. Responses were uncommon among patients with FSGS. Eleven patients (45.8%), all of whom were non-responders, progressed to end-stage kidney disease. No major adverse effects of rituximab were observed; mild infusion reactions occurred in three patients and mild cellulitis in one patient. In this cohort of children with refractory SRNS, favorable responses to rituximab were observed predominantly among patients with CNI-resistant MCD and MCD with IgM deposition, whereas responses among patients with FSGS were uncommon. These findings suggest that renal histopathology may help identify patients more likely to benefit from rituximab therapy; however, the small sample size, heterogeneous histopathological distribution, and observational study design preclude definitive conclusions. Larger prospective multicenter studies incorporating comprehensive genetic evaluation are required to determine whether histopathology can serve as a reliable predictor of rituximab responsiveness.
2026-08-30 | Single-cell transcriptomic signatures of T cells associated with rituximab responsiveness in idiopathic nephrotic syndrome.
Rituximab (RTX) is increasingly used in steroid-dependent minimal change disease, a leading cause of idiopathic nephrotic syndrome (INS), yet predictors of response remain unclear. Although RTX primarily targets B cells, T cells are also implicated in INS pathogenesis. We investigated RTX-induced T cell dynamics by single-cell RNA sequencing/T cell receptor profiling of peripheral T cells from three responders and three non-responders before and after RTX treatment. Responders exhibited RTX-driven broad transcriptomic remodeling, accompanied by reduced exhausted CD8+ T cells and clonal expansion of CD4+ cytotoxic T cells with enhanced oxidative phosphorylation (OXPHOS) signatures, whereas non-responders showed marginal changes. In a separate cohort, reactive oxygen species (ROS) levels tended to be higher in responders, and declined post-RTX, collectively associating enhanced mitochondrial activity with favorable response. Reanalysis of childhood INS data supported altered B-T cell crosstalk and T cell metabolism. Together, T cells may influence RTX responsiveness, warranting further biomarker studies.
2026-08-07 | Anti-rituximab antibodies: implications for clinical outcomes and safety in pediatric idiopathic nephrotic syndrome.
Rituximab (RTX) has been proven effective in the treatment of idiopathic nephrotic syndrome (INS). The development of anti-rituximab antibodies (ARA) may compromise its efficacy and safety. However, the incidence and clinical relevance of ARA in pediatric INS remain incompletely defined. This retrospective study involved 90 pediatric patients with INS who were treated with RTX at a dose of 375 mg/m2 at Jinling Hospital, Affiliated Hospital of Medical School of Nanjing University, China, between March 2024 and May 2025. ARA were detected using a paramagnetic particle chemiluminescence immunoassay. ARA were detected in 30 of 90 patients (33.3%). The incidence of ARA positivity increased progressively with subsequent RTX infusions, rising markedly after the third infusion. ARA-positive patients had a significantly higher relapse rate compared with ARA-negative patients (83.3% vs. 25.0%, p < 0.001), higher CD20⁺ B-cell counts at 3 and 6 months (p < 0.005), and an increased risk of infusion-related reactions (IRR) during multiple RTX infusions (p = 0.019). Multivariate analyses identified younger age at first RTX administration, a higher number of RTX infusions, and occurrence of multiple IRR as independent risk factors for ARA positivity. ARA are associated with impaired B-cell depletion and higher relapse rates. Monitoring ARA may help identify patients at risk of treatment failure and guide individualized therapeutic strategies.
cell therapies
2026-07-03 | Cord blood-derived mesenchymal stromal cells in children with steroid-dependent nephrotic syndrome: a prospective phase II study.
Children with steroid-dependent nephrotic syndrome (SDNS) require long-term immunosuppressive (IS) treatment, significantly impacting their quality of life. Cord-blood-derived mesenchymal stromal cells (CB-MSCs) are multipotent stem cells with proven immunomodulatory properties. We conducted an adaptive, open-label, single-arm, phase II trial with an adaptive second part to evaluate the efficacy of CB-MSCs in children aged 3-18 years with SDNS in remission for ≥6 months on IS therapy. In Part 1, patients received three intravenous infusions of CB-MSCs (1.5 × 10⁶/kg) at 1-2-week intervals, with rapid IS tapering and discontinuation after the third infusion. The primary endpoint was relapse-free survival at 6 months post-IS withdrawal, with a threshold of <4/11 relapsing patients. In the adaptive Part 2, IS was discontinued before the first infusion to enhance CB-MSCs activity, and the dose was increased to 2 × 10⁶/kg, with a booster fourth infusion. A historical cohort of SDNS children tapering IS under standard care served as a post-hoc control. In Part 1, 9 patients were enrolled, and 7/9 (78%) relapsed, failing to meet the prespecified efficacy threshold. In Part 2, 11 patients were enrolled; 9 (82%) were in remission at 2 weeks post-third infusion and received the boosted dose. However, 6/11 (55%) relapsed within 6 months, with no significant difference in relapse-free survival compared to Part 1 (P = .25). Historical controls had significantly better relapse-free survival (P = .0007). In children with SDNS, this novel therapy with CB-MSCs was safe but failed to improve relapse-free survival 6 months after IS withdrawal.
2026-04-12 | Lipoprotein apheresis for anti-nephrin antibody-positive steroid-resistant nephrotic syndrome: a pediatric case report.
Steroid-resistant nephrotic syndrome (SRNS) in children carries a poor prognosis, and recent discoveries implicate anti-nephrin autoantibodies (ANABs) as mediators of podocyte injury. Lipoprotein apheresis, originally developed for familial hypercholesterolemia, has been explored as rescue therapy in refractory SRNS, but its immunologic effects remain uncertain. This case demonstrates a decline in ANAB titers accompanied by clinical improvement following lipoprotein apheresis. We report a 7-year-old male of Afro-Caribbean descent with biopsy findings consistent with minimal change disease and punctate IgG staining who presented with steroid-resistant nephrotic syndrome. He was unresponsive to tacrolimus, rituximab, mycophenolate mofetil, and five therapeutic plasma exchange sessions, and developed severe anasarca requiring extracorporeal ultrafiltration. Compassionate-use lipoprotein apheresis was initiated. Twelve sessions were performed over about ten weeks. Serial plasma ANAB testing showed a marked decrease with lipoprotein apheresis. Clinically, urine output increased, edema resolved, and ultrafiltration was discontinued about seven weeks after the final session, although nephrotic-range proteinuria persisted. This case highlights the potential immunomodulatory role of lipoprotein apheresis in ANAB-mediated podocytopathy. Improvement despite lack of response to therapeutic plasma exchange suggests that lipoprotein apheresis may remove certain antibodies and immune complexes more efficiently compared to conventional therapeutic plasma exchange. Serial ANAB monitoring provided a biomarker correlating with treatment response. Controlled studies are needed to clarify the mechanisms and define the role of lipoprotein apheresis in ANAB-positive SRNS patients.
2025-10-01 | Methods of a Pilot Clinical Trial: Transcutaneous Vagus Nerve Stimulation for the Treatment of Childhood Nephrotic Syndrome
Background: Children with nephrotic syndrome are exposed to prolonged courses of steroids and other immunosuppressant medications with adverse side effect profiles and variable efficacy. There is an urgent need to identify novel and safe therapies to treat nephrotic syndrome in children. Stimulation of the vagus nerve, which can be activated non-invasively by transcutaneous auricular vagus nerve stimulation (taVNS), modulates the immune system by the inflammatory reflex and spleen. The central hypothesis is that activation of the inflammatory reflex via taVNS modulates the immune response, attenuates relapses and proteinuria, and reduces reliance on immunosuppressant medications in children with nephrotic syndrome. The objective is to conduct pilot clinical trials to evaluate the feasibility and tolerability of taVNS for the treatment of nephrotic syndrome in children and generate preliminary data to guide power calculations for a future larger study. Methods: This NIH-funded pilot study will enroll 30 children with FRNS and 10 children with SRNS age 3-17 years from two sites in two parallel, double-blinded, randomized placebo-controlled trials comparing taVNS use for 10 minutes twice a day with sham therapy for 26 weeks. To test for feasibility and tolerability of the clinical trial, the process of recruitment, adherence, device functionality, time and resource utilization, and safety monitoring will be examined. Preliminary data gathered from this pilot study will then be used to determine whether a subsequent larger main trial should move forward. Further, immune markers including serum and monocyte-stimulated cytokines and anti-nephrin antibodies will be measured in order to characterize the immunomodulatory effect of taVNS therapy. Results: The study is currently enrolling participants. Conclusion: Accomplishing the goals of this pilot study will provide preliminary data that will inform the design of and strengthen the implementation of a planned larger clinical trial. Providing these preliminary data that are essential to conduct a large-scale trial will address a significant knowledge gap and will pave the way for evaluation of an innovative, non-pharmacologic, non-invasive, steroid-sparing approach to the treatment of idiopathic nephrotic syndrome in children. Funding: NIDDK Support
2025-07-01 | Early low-density lipoprotein apheresis for steroid-resistant minimal change disease with acute kidney injury: a case report.
We report the case of a 75-year-old woman with steroid-resistant minimal change disease (MCD) whose refractory proteinuria and hypoproteinemia were controlled with early low-density lipoprotein apheresis (LDL-A). She was initially treated with steroid therapy, including methylprednisolone pulse. However, her hypoproteinemia, severe proteinuria, accompanied with renal insufficiency persisted despite these therapies. We initiated hemodialysis on day 17, and LDL-A on day 18. After the treatment, we found an improvement in her urine protein excretion, hyperlipidemia, and hypoproteinemia gradually. Her renal function returned to normal. We added cyclosporine A (CyA) after confirming the normal renal function. Her proteinuria was 0.693 g/day on day 350 and she achieved incomplete remission type I. There are few reports of the efficacy of LDL-A in older patients with MCD with acute kidney injury (AKI). In addition, there are only a few reports of cases in which LDL-A was introduced early, as in this case. This case suggests that early LDL-A may be an effective therapy for steroid-resistant MCD with AKI.
2025-03-04 | Personalized disease recurrence modeling using iPSC-derived podocytes in patients with idiopathic nephrotic syndrome.
Primary focal segmental glomerulosclerosis (FSGS) is characterized by podocyte injury and treatment-resistant nephrotic syndrome. Recurrence of the original disease after kidney transplantation (rFSGS) occurs in 10%-50% of patients. Unidentified circulating permeability factors (CPF) are likely involved in FSGS pathogenesis. We hypothesized that donor podocyte susceptibility to CPF is also relevant. We developed a personalized model for (r)FSGS using induced pluripotent stem cell (iPSC)-derived podocytes from patients and kidney donors. Five patients and their respective living kidney donors were included. Three patients had developed rFSGS, and two patients manifested no symptoms of rFSGS. One patient (P5) had heterozygous mutations in NPHS2. Peripheral blood mononuclear cells were reprogrammed to iPSC, and differentiated to podocytes. iPSC-derived podocytes from either patients or donors were exposed to presumed CPF-containing plasma/serum of corresponding patients. Three assays to detect podocyte injury were performed: (i) reactive oxygen species formation, (ii) cellular granularity induction, and (iii) quantitative assessment of F-actin redistribution (FAR), a new quantitative method. Crossmatch experiments with donor iPSC-derived podocytes and patients samples assessed individual susceptibility to CPF-induced injury. Successful podocyte differentiation was confirmed by morphology and protein expression. Only FAR differentiated consistently between patient and healthy donor samples. All pre-transplant patient samples except P5 caused significant FAR in corresponding patient podocytes. Significant FAR was observed in donor podocytes exposed to corresponding patient samples in the setting of rFSGS, and not in donor podocytes exposed to samples of patients who did not develop rFSGS. Effects of FSGS patient samples on non-corresponding donor podocytes were variable. In vitro assays using iPSC-derived donor podocytes may allow individualized assessment of rFSGS. Prospective studies in a larger cohort are required to validate our findings.
other
2026-06-23 | Genetic Nephrotic Syndrome in Children and Adolescents: An Update.
Idiopathic nephrotic syndrome is one of the most common glomerular diseases in children and adolescents. Monogenic nephrotic syndrome is associated with lower rates of remission following treatment with standard immunosuppressive therapies and a higher risk of progression to end-stage kidney disease. Advances in genetic testing technologies have identified more than 100 single-gene causes of nephrotic syndrome and made genetic testing more accessible in clinical practice. The vast majority of genes implicated in the etiology of nephrotic syndrome are associated with the glomerular filtration barrier and primarily with the podocyte. A molecular diagnosis of nephrotic syndrome has implications for medication choice, prognostication, indications for further testing, and transplant planning. Like all clinical tools, however, it must be utilized in the appropriate clinical context, though no standardized guidelines exist for indications for genetic testing in nephrotic syndrome. Standard treatment of nephrotic syndrome consists of immunosuppressive therapies. However, patients with monogenic nephrotic syndrome are less likely to achieve remission with immunosuppression, and alternative treatment options are under investigation.
2025-12-27 | Nephrotic syndrome genomic discovery in the Mass General Brigham Biobank identifies monoallelic MEFV variants as a risk factor for focal segmental glomerulosclerosis.
Health system-based biobanks with genetic data provide a unique opportunity for nephrotic syndrome (NS) genomic discovery. This is predicated on finding cases in the electronic health record. We tested three strategies to identify focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD) cases in the 130,000 members of Mass General Brigham Biobank (MGBB). We analyzed a "synthetic proteinuria panel" of 192 Mendelian genes and the APOL1 kidney risk variants in those with exome sequencing (ES). We studied the associations between patients with Mendelian variants (MV), APOL1-HR genotype (APOL1) and outcomes. Validation of a novel gene-FSGS association was done in the Genomics England 100,000 Genome Project (100KG) and a global NS case-control cohort. 319 MGBB participants had FSGS or MCD and ES data; reviewing pathology reports was the most accurate screening strategy. 31 (9.7%) of patients had MV and 24 (7.5%) had APOL1. 61% of genetic NS with a kidney biopsy report were classified as secondary FSGS. MV and APOL1 patients had a 3.1 (1.1-8.7) and 6.5 (1.3-32.3) increased odds of developing kidney failure, respectively. Unexpectedly, monoallelic pathogenic variants in MEFV (Mendelian gene for Familial Mediterranean Fever [FMF]) were found in 6 MGBB participants with FSGS, all of whom had features of collapsing glomerulopathy and thrombotic microangiopathy. 8 glomerular disease cases in the 100KG, unsolved via genome sequencing, had monoallelic pathogenic MEFV variants. Finally, a case-control study found a 3.8 increased odds of SRNS in individuals with pathogenic or likely pathogenic MEFV alleles (P = 7.8 × 10-5). 17.2% of unselected adults with NS in the MGBB had a well-established genetic form, each associated with an increased risk of kidney failure. A biopsy read of secondary FSGS should not be used to rule out testing for genetic disease. Monoallelic pathogenic variants in MEFV may be a novel and underappreciated cause or susceptibility factor for SRNS/FSGS with distinct histologic features, even in the absence of clinical FMF.
2025-06-28 | The Efficacy of Pneumococcal and Influenza Vaccination in Prevention of Relapse of Steroid-Sensitive Nephrotic Syndrome in Children
Abstract Background: Nephrotic syndrome (NS) is a common disorder in the pediatric age group. The majority of them developed relapse due to infection. About 50%–70% relapses occur due to respiratory tract infection. Therefore, pneumococcal and influenza vaccination may prevent the number of relapses. Materials and Methods: This prospective, case–control study was carried out in the department of Pediatric Nephrology, Bangabandhu Sheikh Mujib Medical University, Dhaka, from November 2016 to February 2018. A total of 120 patients aged 2–18 years old with an initial episode of idiopathic NS (INS) were included in this study. They were divided in two groups according to age and administration of the Haemophilus influenzae vaccine: Group A and Group B. Group A included 60 children of younger age group (2–8 years). All of them received Haemophilus influenzae vaccine through the Expanded Program on Immunization (EPI) schedule. They were further subdivided into two subgroups: Group A1 and Group A2. Group A1 included 30 children who received pneumococcal and influenza vaccines. Group A2 also included 30 children who refused vaccination. Similarly, Group B included 60 children, and they belonged to the older age group (>8–18 years). They did not receive Haemophilus influenzae vaccine through the EPI schedule. They were further subdivided into two subgroups: Group B1 and Group B2. Group B1 included 30 children who received pneumococcal and influenza vaccine. Group B2 also included 30 children who refused vaccination. All of them were followed up for 1 year to compare the clinical effects. Results: A total of 120 patients were studied. Among them, the number of patients without relapses was high in the younger age vaccinated group than non-vaccinated group (36.7% vs. 10%; P = 0.003). In addition to this, older age vaccinated group developed less relapses compared to the non-vaccinated group ( P < 0.05). This indicates that vaccination has a beneficial role in preventing relapse in children with INS. Conclusion: Vaccination against pneumococcus and influenza lowers relapses in children with INS.
2025-05-22 | Association between SIRT-1 and SERPINA4 gene polymorphisms and the risk of idiopathic nephrotic syndrome among Egyptian children.
Idiopathic nephrotic syndrome (INS) is the primary cause of chronic glomerular dysfunction in children. Despite extensive research, its pathophysiology remains unclear, particularly in cases that are resistant to steroids. This research evaluated the impact of SIRT-1 (rs2273773) and SERPINA4 (rs2093266) gene variants on Egyptian children's susceptibility to INS and response to steroid therapy. Genetic polymorphisms of SIRT-1 (rs2273773) and SERPINA4 (rs2093266) were screened in 135 INS children and a similar number of healthy volunteers using real-time PCR. Concerning SIRT-1 rs2273773 genotypes, the cases showed markedly greater CT, TT genotypes, and T allele incidences than the reference group, which increased the risk of INS by 2.01-, 4.03-, and 1.88-folds, respectively. Regarding SERPINA4 rs2093266 genotypes, the cases exhibited notably higher GA, AA genotypes, and the A allele frequencies than controls, which enlarged the risk of INS by 3.1-, 5.47-, and 2.82-folds, respectively. The frequency of GA and AA genotypes and the presence of the A allele of SERPINA4 rs2093266 were considerably higher in steroid-resistant versus steroid-sensitive cases. The logistic regression model stated the serum creatinine, blood urea nitrogen, and the SERPINA4 rs2093266 polymorphism as independent contributors to the risk for steroid resistance in INS cases. SIRT-1 (rs2273773) and SERPINA4 (rs2093266) gene polymorphisms significantly attributed to the risk of developing INS in Egyptian children. Furthermore, the SERPINA4 (rs2093266) polymorphism has a strong correlation with steroid resistance, suggesting that it could be a target for treatment to avoid severe renal problems and adverse steroid effects.
2024-11-27 | NPHS Mutations in Pediatric Patients with Congenital and Steroid-Resistant Nephrotic Syndrome.
NPHS1 and NPHS2 are kidney gene components that encode for nephrin and podocin, respectively. They play a role in the progression of congenital (CNS) and steroid-resistant (SRNS) nephrotic syndrome. Hence, this study aimed to determine the prevalence and renal outcomes of NPHS mutations among pediatric patients with CNS and SRNS. We also aimed to identify potential predictors of NPHS mutations in this patient cohort. Overall, this study included 33 studies involving 2123 patients screened for NPHS1, whereas 2889 patients from 40 studies were screened for NPHS2 mutations. The patients' mean age was 4.9 ± 1 years (ranging from birth to 18 years), and 56% of patients were male (n = 1281). Using the random-effects model, the pooled proportion of NPHS1 mutations among pediatric patients with CNS and SRNS was 0.15 (95% CI 0.09; 0.24, p < 0.001, I2 = 92.0%). The pooled proportion of NPHS2 mutations was slightly lower, at 0.11 (95% CI 0.08; 0.14, p < 0.001, I2 = 73.8%). Among the 18 studies that reported ESRF, the pooled proportion was 0.47 (95% CI 0.34; 0.61, p < 0.001, I2 = 75.4%). Our study showed that the NPHS1 (β = 1.16, p = 0.35) and NPHS2 (β = 5.49, p = 0.08) mutations did not predict ESRF in CNS and SRNS pediatric patients. Nevertheless, patients from the European continent who had the NPHS2 mutation had a significantly higher risk of developing ESRF (p < 0.05, β = 1.3, OR = 7.97, 95% CI 0.30; 2.30) compared to those who had the NPHS1 mutation. We recommend NPHS mutation screening for earlier diagnosis and to avoid unnecessary steroid treatments. More data are needed to better understand the impact of NPHS mutations among pediatric patients with CNS and SRNS.
small molecules
2026-09-24 | [The value of immuno-histochemical analysis of renal glucocorticoid receptor expression in idiopathic nephrotic syndrome].
The response to corticosteroid therapy in idiopathic nephrotic syndrome (INS) is variable. Glucocorticoid receptors (GR), which are essential for steroid action, may partly explain this variability. To investigate the relationship between podocyte glucocorticoid receptor expression assessed by immunohistochemistry and the response to corticosteroid therapy in INS. This was a retrospective study conducted over a 22-year period, including 29 patients with minimal change disease or primary focal segmental glomerulosclerosis. Podocyte GR expression was evaluated by immunohistochemistry and correlated with treatment response. In total, 18 patients were steroid-sensitive, 6 were steroid-dependent, and 5 were steroid-resistant. No conventional clinical, laboratory, or histological factor was predictive. However, GR expression was higher in steroid-sensitive than in steroid-resistant patients (p = 0.046). Podocyte glucocorticoid receptor expression may predict the response to corticosteroid therapy in idiopathic nephrotic syndrome.
2026-09-22 | Thromboembolic prophylaxis in childhood idiopathic nephrotic syndrome. From pathophysiology to clinical management
Thromboembolic complications remain among the most serious complications of childhood idiopathic nephrotic syndrome (INS). Although their incidence is considerably lower than in adults, venous thromboembolism continues to cause substantial morbidity and occasional mortality, including pulmonary embolism, cerebral venous sinus thrombosis, and extensive deep venous thrombosis. Preventive management remains controversial because most affected children may not develop thrombosis, whereas pharmacological prophylaxis exposes many low-risk patients to potential overtreatment. Current recommendations are largely based on retrospective studies, expert opinions, and extrapolation from adult nephrotic syndrome, while prospective pediatric evidence remains scarce. This review examines the contemporary understanding of thrombogenesis in childhood INS, emphasizing that hypercoagulability extends beyond urinary antithrombin loss to involve hepatic overproduction of procoagulant factors, impaired fibrinolysis, platelet activation, endothelial dysfunction, and hemoconcentration. We also discuss the possibility that historical thrombotic risk may have been amplified by prolonged corticosteroid exposure and consider whether the widespread adoption of steroid-sparing immunosuppressive therapies and earlier relapse detection may have modified the epidemiology of thromboembolism in the modern therapeutic era. Current preventive strategies—including no routine prophylaxis, biomarker-guided individualized approaches, aspirin, and prophylactic low-molecular-weight heparin (LMWH)—are critically reviewed. We argue that increasingly complex biomarker-based algorithms have not demonstrated clear clinical superiority over simple, pragmatic decision-making. Severe hypoalbuminemia provides a pragmatic surrogate of nephrotic severity and may therefore help identify children in whom the overall prothrombotic state is likely to be substantial. We are not proposing albumin <20 g/L as a validated predictor of thrombosis. We are proposing it as a pragmatic clinical trigger for considering prophylaxis in a disease in which no validated predictive model currently exists. We propose a pragmatic risk-stratified approach in which routine pharmacological prophylaxis is unnecessary for early biochemical relapses with minimal clinical manifestations but should be strongly considered in children and adolescents with clinically significant active nephrotic syndrome associated with severe hypoalbuminemia (approximately <20 g/L), provided no major contraindications exist. Where feasible, LMWH appears to be the most appropriate prophylactic agent. Until prospective pediatric studies better define thrombotic risk and validate prediction models, practical consistency based on clinically meaningful risk thresholds may provide a more rational framework than theoretical precision for thromboprophylaxis in childhood INS.
2026-09-03 | Efficacy and safety of 5-day versus 7-day antibiotic therapy for spontaneous bacterial peritonitis in children with idiopathic nephrotic syndrome: an open-label randomized controlled trial.
Spontaneous bacterial peritonitis (SBP) is a life-threatening complication of idiopathic nephrotic syndrome (INS) in children. Evidence on the optimal duration of antibiotics in this population is limited. We investigated whether 5-day antibiotic therapy is non-inferior to 7-day therapy for SBP in children with INS. In this single-center, open-label, randomized controlled non-inferiority trial, 50 children aged 1-14 years with INS and SBP were allocated 1:1 to intravenous ceftriaxone for 5 days (Group A, n = 25) or 7 days (Group B, n = 25). The primary outcome was composite clinical response (resolution of fever, abdominal pain, and tenderness) at the end of treatment, analyzed by intention-to-treat. The pre-specified non-inferiority margin was -15%. Secondary outcomes included bacteriological cure, cytological response, and the need for additional antibiotics. Fifty children [median age 50 (30.8-92) months] were randomized. Composite clinical response was achieved in 25/25 (100%) in Group A versus 22/25 (88%) in Group B (risk difference 12%, 95% CI -3.5% to 30.0%; P = 0.23); the lower CI bound exceeded the -15% non-inferiority margin, establishing non-inferiority. Bacteriological cure was achieved in 96% of both groups. Cytological response (64% vs 72%; P = 0.54) was inconclusive for non-inferiority. Additional or modified antibiotic therapy was required in 16% versus 20% (P = 1.00). Median hospitalization was comparable (10 vs 11 days; P > 0.05). No ceftriaxone-related adverse events were recorded. Five-day intravenous ceftriaxone is non-inferior to 7-day therapy for SBP in children with INS, with respect to composite clinical response; the secondary outcome of cytological response was inconclusive for non-inferiority.
2026-07-27 | Paraneoplastic Minimal Change Disease Signaling Post-Transplant AML Relapse: Two Cases and a Literature Review.
Membranous nephropathy (MN) and minimal change disease (MCD) are the most common causes of nephrotic syndrome following hematopoietic stem cell transplantation (HSCT), a complication conventionally attributed to chronic graft-versus-host disease (GVHD). Paraneoplastic MCD is well described in lymphoid malignancies but is rarely reported in myeloid neoplasms. We report two cases of biopsy-confirmed MCD presenting as the initial manifestation of acute myeloid leukemia (AML) relapse following allogeneic HSCT. Both patients were White men in their sixties with relapsed/refractory AML who developed nephrotic-range proteinuria and acute kidney injury after matched unrelated donor HSCT without histologic evidence of GVHD. Renal biopsies confirmed MCD in both cases. Corticosteroid therapy was ineffective in halting renal deterioration; renal function improved only after initiation of leukemia-directed therapy, with one patient achieving dialysis independence. These cases highlight a rare paraneoplastic presentation of AML relapse. Nephrotic syndrome due to MCD may signal post-HSCT leukemia recurrence, and evaluation for AML relapse warrants consideration in steroid-refractory cases or those without concurrent GVHD. In such cases, control of the underlying malignancy, rather than escalation of immunosuppression, may be central to renal recovery.
2026-07-12 | Cerebral venous sinus thrombosis secondary to relapsed minimal change disease: a case managed with endovascular thrombolysis.
Cerebral venous sinus thrombosis (CVST) is a rare type of stroke characterized by the formation of blood clots within the dural venous sinuses which has a high mortality rate. Despite its potential severity, cerebral venous sinus thrombosis secondary to nephrotic syndrome remains rarely reported and under-recognized in clinical practice. We described a 20-year-old male who presented with a relapse of minimal change disease, complicated by extensive CVST. On the basis of anticoagulant therapy, his neurological condition deteriorated rapidly, manifesting as altered mental consciousness, progressive limb weakness, and new-onset seizures. Given the failure of conventional medical management, endovascular therapy of catheter-directed thrombolysis was performed. The patient's neurological status improved dramatically within days. This case demonstrates that cerebral venous sinus thrombosis should be considered in nephrotic syndrome patients presenting with even subtle or non-specific neurological symptoms. Patients with focal neurological deficits, altered mental status, new-onset seizures, or unusual headache should undergo prompt neurological evaluation and appropriate brain imaging, including computed tomography venography (CTV) or magnetic resonance venography (MRV) when CVST is suspected. In the specific setting of nephrotic syndrome, clinicians should maintain a heightened index of suspicion for CVST, even when initial neurological findings are subtle or non-specific. As illustrated by this case, early recognition and timely escalation to endovascular therapy can be life-saving when conventional anticoagulation fails to prevent neurological deterioration. Our patient achieved complete neurological recovery and sustained remission of nephrotic syndrome, underscoring the value of multidisciplinary collaboration and individualized treatment strategies.
proteins
2026-09-23 | Comparison of Albumin versus Fresh Frozen Plasma in the Treatment of Children with Diuretic-Resistant Oedema in Idiopathic Nephrotic Syndrome at a Tertiary Hospital
Comparison of Albumin versus Fresh Frozen Plasma in the Treatment of Children with Diuretic-Resistant Oedema in Idiopathic Nephrotic Syndrome at a Tertiary Hospital
2026-06-19 | IgM Hyposialylation Modulates Podocyte Vulnerability in Patients With Idiopathic Nephrotic Syndrome.
Altered Ig glycosylation has been implicated in antibody-mediated podocytopathies; however, the functional relevance of IgM sialylation remains poorly defined. Previous evidence suggests that circulating cationic or hyposialylated IgM may contribute to podocyte vulnerability in idiopathic nephrotic syndrome (iNS). Serum IgM from 86 pediatric and adult patients with podocytopathies, 20 patients with membranous nephropathy (MN), 20 patients with lupus nephritis (LN), and 30 healthy controls were analyzed by lectin-based enzyme-linked immunosorbent assay (ELISA) using biotinylated lectins to assess terminal N-glycan residues, including Sambucus nigra agglutinin (SNA) and Ricinus communis agglutinin I (RCA-I). Serum levels of the sialyltransferase ST6GAL1 and the sialidases neuraminidase-1 (NEU1) and neuraminidase-3 (NEU3) were quantified. Cultured human podocytes were exposed to native, desialylated, or resialylated IgM and analyzed by confocal microscopy, quantitative proteomics, phosphoproteomics, and metabolic assays. IgM from patients with iNS showed reduced SNA binding, which inversely correlated with proteinuria and circulating NEU1/NEU3 levels. In paired samples, SNA reactivity decreased during relapse and increased during remission. ST6GAL1 was undetectable across all groups, whereas phospholipase A2 receptor 1(PLA2R1)-positive MN displayed reduced RCA-I binding. Podocytes exposed to hyposialylated or desialylated IgM exhibited disorganization of the actin cytoskeleton, reduced nephrin signal, increased lipid peroxidation, and decreased ATP levels. Resialylated IgM displayed podocyte morphological and metabolic features not statistically distinguishable from those observed under control conditions. Proteomic and phosphoproteomic analyses highlighted modulation of mitogen-activated protein kinase (MAPK)-, mechanistic Target of Rapamycin (mTOR-), adenosine monophosphate-activated protein kinase (AMPK), and cytoskeleton-related pathways. IgM sialylation status tracks disease activity and modulates podocyte structural, metabolic, and signaling responses, supporting immune glycan remodeling as a disease-associated modifier of podocyte vulnerability in iNS.
2026-01-10 | Celiac Disease in Children with Idiopathic Nephrotic Syndrome-A Retrospective Cohort Study.
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.
2026-01-01 | Coexistence of idiopathic nephrotic syndrome, celiac disease, and dermatitis herpetiformis: a rare paediatric case report
Idiopathic nephrotic syndrome (INS) is the most common cause of nephrotic syndrome in childhood.Celiac disease is an autoimmune gluten-dependent enteropathy, and dermatitis herpetiformis (Duhring's disease) represents its most frequent extraintestinal manifestation.The coexistence of INS, celiac disease, and dermatitis herpetiformis constitutes an exceptionally rare clinical finding.We present the case of a 13-year-old girl diagnosed with all three conditions.Following the introduction of a gluten-free diet, complete remission of both nephrological and dermatological symptoms was achieved.This case highlights the importance of an interdisciplinary diagnostic and therapeutic approach and the need to consider gluten-related disorders in children with INS of atypical presentation.
2025-11-05 | IgM hyposialylation drives podocyte injury in pediatric and young adult patients with podocytopathies
Abstract Introduction Altered immunoglobulin glycosylation has been implicated in antibody-mediated podocytopathies, yet the functional impact of IgM sialylation remains unclear. Previous evidence suggested that circulating cationic or hyposialylated IgM may contribute to podocyte injury in idiopathic nephrotic syndrome (iNS). Methods Serum IgM from pediatric and young adult patients with podocytopathies, membranous nephropathy (MN), lupus nephritis (LN), and healthy controls were analyzed by lectin-based ELISA using a panel of six biotinylated lectins to detect terminal N-glycan residues. Among these, Sambucus nigra agglutinin (SNA) binds α2,6-linked sialic acid, and Ricinus communis agglutinin I (RCA-I) recognizes β1,4-linked galactose. Serum levels of the α2,6-sialyltransferase ST6GAL1 and the sialidases neuraminidase-1 (NEU1) and neuraminidase-3 (NEU3) were quantified. Cultured human podocytes were exposed to patient-derived, control, or enzymatically modified IgM (desialylated/resialylated) and analyzed by confocal microscopy, quantitative proteomics, phosphoproteomics, and metabolic assays. Results IgM from patients with podocytopathies showed reduced SNA binding, which inversely correlated with proteinuria (r = −0.69, P < 0.0001) and with serum sialidases NEU1/NEU3 (r = −0.67/−0.59, P < 0.0001). In paired samples, SNA reactivity decreased during relapse and normalized in remission, indicating dynamic modulation with disease activity. ST6GAL1 was undetectable in all groups. In contrast, PLA2R1-positive MN, in which pathogenic antibodies target podocyte PLA2R1, displayed reduced RCA-I binding. Podocytes exposed to hyposialylated or desialylated IgM exhibited actin disorganization, loss of nephrin signal, increased lipid peroxidation, and decreased ATP synthesis. In contrast, resialylated IgM preserved morphology and metabolism comparable to controls. Proteomic and phosphoproteomic profiling revealed enrichment of MAPK, mTOR, AMPK, and cytoskeletal remodeling pathways. Conclusions IgM hyposialylation, driven by extracellular sialidases up-regulation, correlates with disease activity and promotes oxidative stress, mitochondrial dysfunction, and cytoskeletal remodeling in podocytes, identifying immune glycan remodeling as a modifiable determinant of podocyte injury and a potential biomarker of disease activity. Translational Statement Altered glycosylation of circulating immunoglobulins is emerging as a key mechanism underlying glomerular injury. Here, we demonstrate that hyposialylated IgM, resulting from elevated serum sialidases NEU1 and NEU3, directly induces podocyte cytoskeletal disorganization, oxidative stress, and metabolic impairment. In contrast, enzymatic resialylation maintains podocyte morphology and function at levels indistinguishable from controls, indicating that sialic acid loss is a modifiable determinant of podocyte injury. Clinically, reduced IgM sialylation correlates with proteinuria and disease activity in idiopathic nephrotic syndrome, supporting its potential as a biomarker of relapse and remission. Targeting the sialidase–sialic acid pathway may therefore represent a promising strategy to preserve podocyte integrity and improve outcomes in antibody-negative podocytopathies.
antibodies
2026-09-27 | Long-term outcomes of childhood nephrotic syndrome.
Idiopathic nephrotic syndrome (INS) is the most common chronic glomerular disease in children. Corticosteroids remain first-line therapy, and the initial response, differentiating steroid-sensitive (SSNS) from steroid-resistant (SRNS) forms, is the strongest prognostic factor. While most childhood-onset INS results from an incompletely defined dysregulation of the immune system, up to one-third of children with initial SRNS have a monogenic etiology. SSNS typically follows a relapsing-remitting course, with one-half of the patients having frequent relapses or steroid-dependence (FRNS/SDNS). Although earlier studies suggested that most SSNS patients achieve sustained remission by puberty, approximately one-fourth experience at least one relapse in adulthood. Key predictors of persistent relapsing disease include FRNS/SDNS in childhood and the need for second-line immunosuppression. The disease may evolve into secondary steroid-resistance in <10% patients with SSNS. Kidney failure and death remain uncommon. In contrast, SRNS is associated with higher risks of therapy-and disease-related complications, including growth impairment, obesity, hypertension and cardiovascular risk, osteoporosis, cataracts, calcineurin inhibitor-induced nephrotoxicity, acute kidney injury and progressive chronic kidney disease. The risk of kidney failure is three- to fourfold higher in patients with monogenic and/or multidrug-resistant SRNS. This review synthesizes current evidence on the long-term outcomes of childhood-onset INS, highlights risk stratification across clinical phenotypes, genetic diagnosis and treatment response, and challenges during transition to adult care.
2026-09-24 | Recent key advances in the understanding of the pathogenesis of childhood minimal change disease.
Minimal change disease (MCD) is the leading cause of idiopathic nephrotic syndrome in children, accounting for >85% of cases in those aged 1-12 years. Although 80%-90% of patients achieve initial remission with glucocorticoids, steroid dependence or frequent relapses occur in 55%-60% of cases, necessitating prolonged immunosuppression. Long-term steroid exposure in children is associated with severe age-specific adverse events, including growth retardation, skeletal dysplasia, cataracts, and impaired vaccine responses from immunosuppression. Steroid resistance and chronic kidney disease may also develop in some patients. Recent clinical evidence and literature (2015-2025) have transformed our understanding of MCD from the traditional "single T cell-driven" hypothesis to a multidimensional interactive regulatory network. This network is based on coordinated T- and B-cell dysregulation, mediated by defined podocyte injury pathways and modulated by genetic and environmental factors. Distinct pediatric traits stem from immature immune system development and pediatric podocyte plasticity. In this review, we synthesize recent advances in these pediatric pathogenic mechanisms, delineate age-dependent differences between childhood and adult MCD, and propose a precision medicine framework for disease subtyping, noninvasive biomarker development, and targeted therapies. This work addresses critical unmet clinical needs in the long-term management of pediatric MCD.
2026-09-03 | Outcome of children treated with rituximab for steroid-resistant nephrotic syndrome: Renal histopathology as a response marker.
Steroid-resistant nephrotic syndrome (SRNS) in children remains a major therapeutic challenge. Although calcineurin inhibitors (CNIs) are commonly used as first-line therapy, a substantial proportion of patients fail to achieve remission, and prolonged use may result in nephrotoxicity. Rituximab has emerged as a potential therapeutic option for refractory SRNS; however, treatment responses appear variable, and the influence of underlying renal histopathology remains incompletely understood. The objective of the study was to evaluate the association between renal histopathological findings and clinical response to rituximab in children with CNI-resistant SRNS. Study design and setting: This prospective observational study was conducted between 2011 and 2020 at a university-affiliated tertiary pediatric nephrology center. The study aimed to evaluate the efficacy of rituximab in children with CNI-resistant SRNS and to examine the association between renal histopathological findings and treatment response. Twenty-four children aged 2-12 years were enrolled. Follow-up: Patients were followed prospectively after completion of rituximab therapy through regular clinical and laboratory assessments. The mean follow-up duration after the last rituximab infusion was 5.1 years (range: 6 months-8 years). treatment response definitions: Complete remission was defined according to International Pediatric Nephrology Association recommendations as a urine protein-to-creatinine ratio (UPCR) ≤20 mg/mmol (≤0.2 mg/mg) or negative/trace proteinuria on dipstick testing on at least three consecutive occasions. Partial remission was defined as a UPCR >20 mg/mmol but <200 mg/mmol together with serum albumin ≥30 g/L. No response was defined as failure to achieve either complete or partial remission. Genetic evaluation: Genetic testing was performed in all patients with focal segmental glomerulosclerosis (FSGS), classic minimal change disease (MCD), and MCD with immunoglobulin M (IgM) deposition. No pathogenic or likely pathogenic variants associated with monogenic SRNS were identified in the tested patients. Genetic testing was not performed in patients with IgA nephropathy, membranous nephropathy, C1q nephropathy, or dense deposit disease (DDD). Twenty-four children with SRNS were included (13 males and 11 females; age range 2-12 years). Histopathological diagnoses included FSGS in nine patients (37.5%), MCD in 4 (16.7%), MCD with IgM deposition in 6 (25.0%), DDD in 2 (8.3%), membranous nephropathy in 1 (4.2%), IgA nephropathy in 1 (4.2%), and C1q nephropathy in 1 (4.2%). Overall, 10 patients (41.7%) achieved complete remission and 3 (12.5%) achieved partial remission, predominantly among patients with MCD and MCD with IgM deposition. Responses were uncommon among patients with FSGS. Eleven patients (45.8%), all of whom were non-responders, progressed to end-stage kidney disease. No major adverse effects of rituximab were observed; mild infusion reactions occurred in three patients and mild cellulitis in one patient. In this cohort of children with refractory SRNS, favorable responses to rituximab were observed predominantly among patients with CNI-resistant MCD and MCD with IgM deposition, whereas responses among patients with FSGS were uncommon. These findings suggest that renal histopathology may help identify patients more likely to benefit from rituximab therapy; however, the small sample size, heterogeneous histopathological distribution, and observational study design preclude definitive conclusions. Larger prospective multicenter studies incorporating comprehensive genetic evaluation are required to determine whether histopathology can serve as a reliable predictor of rituximab responsiveness.
2026-08-30 | Single-cell transcriptomic signatures of T cells associated with rituximab responsiveness in idiopathic nephrotic syndrome.
Rituximab (RTX) is increasingly used in steroid-dependent minimal change disease, a leading cause of idiopathic nephrotic syndrome (INS), yet predictors of response remain unclear. Although RTX primarily targets B cells, T cells are also implicated in INS pathogenesis. We investigated RTX-induced T cell dynamics by single-cell RNA sequencing/T cell receptor profiling of peripheral T cells from three responders and three non-responders before and after RTX treatment. Responders exhibited RTX-driven broad transcriptomic remodeling, accompanied by reduced exhausted CD8+ T cells and clonal expansion of CD4+ cytotoxic T cells with enhanced oxidative phosphorylation (OXPHOS) signatures, whereas non-responders showed marginal changes. In a separate cohort, reactive oxygen species (ROS) levels tended to be higher in responders, and declined post-RTX, collectively associating enhanced mitochondrial activity with favorable response. Reanalysis of childhood INS data supported altered B-T cell crosstalk and T cell metabolism. Together, T cells may influence RTX responsiveness, warranting further biomarker studies.
2026-08-07 | Anti-rituximab antibodies: implications for clinical outcomes and safety in pediatric idiopathic nephrotic syndrome.
Rituximab (RTX) has been proven effective in the treatment of idiopathic nephrotic syndrome (INS). The development of anti-rituximab antibodies (ARA) may compromise its efficacy and safety. However, the incidence and clinical relevance of ARA in pediatric INS remain incompletely defined. This retrospective study involved 90 pediatric patients with INS who were treated with RTX at a dose of 375 mg/m2 at Jinling Hospital, Affiliated Hospital of Medical School of Nanjing University, China, between March 2024 and May 2025. ARA were detected using a paramagnetic particle chemiluminescence immunoassay. ARA were detected in 30 of 90 patients (33.3%). The incidence of ARA positivity increased progressively with subsequent RTX infusions, rising markedly after the third infusion. ARA-positive patients had a significantly higher relapse rate compared with ARA-negative patients (83.3% vs. 25.0%, p < 0.001), higher CD20⁺ B-cell counts at 3 and 6 months (p < 0.005), and an increased risk of infusion-related reactions (IRR) during multiple RTX infusions (p = 0.019). Multivariate analyses identified younger age at first RTX administration, a higher number of RTX infusions, and occurrence of multiple IRR as independent risk factors for ARA positivity. ARA are associated with impaired B-cell depletion and higher relapse rates. Monitoring ARA may help identify patients at risk of treatment failure and guide individualized therapeutic strategies.
cell therapies
2026-07-03 | Cord blood-derived mesenchymal stromal cells in children with steroid-dependent nephrotic syndrome: a prospective phase II study.
Children with steroid-dependent nephrotic syndrome (SDNS) require long-term immunosuppressive (IS) treatment, significantly impacting their quality of life. Cord-blood-derived mesenchymal stromal cells (CB-MSCs) are multipotent stem cells with proven immunomodulatory properties. We conducted an adaptive, open-label, single-arm, phase II trial with an adaptive second part to evaluate the efficacy of CB-MSCs in children aged 3-18 years with SDNS in remission for ≥6 months on IS therapy. In Part 1, patients received three intravenous infusions of CB-MSCs (1.5 × 10⁶/kg) at 1-2-week intervals, with rapid IS tapering and discontinuation after the third infusion. The primary endpoint was relapse-free survival at 6 months post-IS withdrawal, with a threshold of <4/11 relapsing patients. In the adaptive Part 2, IS was discontinued before the first infusion to enhance CB-MSCs activity, and the dose was increased to 2 × 10⁶/kg, with a booster fourth infusion. A historical cohort of SDNS children tapering IS under standard care served as a post-hoc control. In Part 1, 9 patients were enrolled, and 7/9 (78%) relapsed, failing to meet the prespecified efficacy threshold. In Part 2, 11 patients were enrolled; 9 (82%) were in remission at 2 weeks post-third infusion and received the boosted dose. However, 6/11 (55%) relapsed within 6 months, with no significant difference in relapse-free survival compared to Part 1 (P = .25). Historical controls had significantly better relapse-free survival (P = .0007). In children with SDNS, this novel therapy with CB-MSCs was safe but failed to improve relapse-free survival 6 months after IS withdrawal.
2026-04-12 | Lipoprotein apheresis for anti-nephrin antibody-positive steroid-resistant nephrotic syndrome: a pediatric case report.
Steroid-resistant nephrotic syndrome (SRNS) in children carries a poor prognosis, and recent discoveries implicate anti-nephrin autoantibodies (ANABs) as mediators of podocyte injury. Lipoprotein apheresis, originally developed for familial hypercholesterolemia, has been explored as rescue therapy in refractory SRNS, but its immunologic effects remain uncertain. This case demonstrates a decline in ANAB titers accompanied by clinical improvement following lipoprotein apheresis. We report a 7-year-old male of Afro-Caribbean descent with biopsy findings consistent with minimal change disease and punctate IgG staining who presented with steroid-resistant nephrotic syndrome. He was unresponsive to tacrolimus, rituximab, mycophenolate mofetil, and five therapeutic plasma exchange sessions, and developed severe anasarca requiring extracorporeal ultrafiltration. Compassionate-use lipoprotein apheresis was initiated. Twelve sessions were performed over about ten weeks. Serial plasma ANAB testing showed a marked decrease with lipoprotein apheresis. Clinically, urine output increased, edema resolved, and ultrafiltration was discontinued about seven weeks after the final session, although nephrotic-range proteinuria persisted. This case highlights the potential immunomodulatory role of lipoprotein apheresis in ANAB-mediated podocytopathy. Improvement despite lack of response to therapeutic plasma exchange suggests that lipoprotein apheresis may remove certain antibodies and immune complexes more efficiently compared to conventional therapeutic plasma exchange. Serial ANAB monitoring provided a biomarker correlating with treatment response. Controlled studies are needed to clarify the mechanisms and define the role of lipoprotein apheresis in ANAB-positive SRNS patients.
2025-10-01 | Methods of a Pilot Clinical Trial: Transcutaneous Vagus Nerve Stimulation for the Treatment of Childhood Nephrotic Syndrome
Background: Children with nephrotic syndrome are exposed to prolonged courses of steroids and other immunosuppressant medications with adverse side effect profiles and variable efficacy. There is an urgent need to identify novel and safe therapies to treat nephrotic syndrome in children. Stimulation of the vagus nerve, which can be activated non-invasively by transcutaneous auricular vagus nerve stimulation (taVNS), modulates the immune system by the inflammatory reflex and spleen. The central hypothesis is that activation of the inflammatory reflex via taVNS modulates the immune response, attenuates relapses and proteinuria, and reduces reliance on immunosuppressant medications in children with nephrotic syndrome. The objective is to conduct pilot clinical trials to evaluate the feasibility and tolerability of taVNS for the treatment of nephrotic syndrome in children and generate preliminary data to guide power calculations for a future larger study. Methods: This NIH-funded pilot study will enroll 30 children with FRNS and 10 children with SRNS age 3-17 years from two sites in two parallel, double-blinded, randomized placebo-controlled trials comparing taVNS use for 10 minutes twice a day with sham therapy for 26 weeks. To test for feasibility and tolerability of the clinical trial, the process of recruitment, adherence, device functionality, time and resource utilization, and safety monitoring will be examined. Preliminary data gathered from this pilot study will then be used to determine whether a subsequent larger main trial should move forward. Further, immune markers including serum and monocyte-stimulated cytokines and anti-nephrin antibodies will be measured in order to characterize the immunomodulatory effect of taVNS therapy. Results: The study is currently enrolling participants. Conclusion: Accomplishing the goals of this pilot study will provide preliminary data that will inform the design of and strengthen the implementation of a planned larger clinical trial. Providing these preliminary data that are essential to conduct a large-scale trial will address a significant knowledge gap and will pave the way for evaluation of an innovative, non-pharmacologic, non-invasive, steroid-sparing approach to the treatment of idiopathic nephrotic syndrome in children. Funding: NIDDK Support
2025-07-01 | Early low-density lipoprotein apheresis for steroid-resistant minimal change disease with acute kidney injury: a case report.
We report the case of a 75-year-old woman with steroid-resistant minimal change disease (MCD) whose refractory proteinuria and hypoproteinemia were controlled with early low-density lipoprotein apheresis (LDL-A). She was initially treated with steroid therapy, including methylprednisolone pulse. However, her hypoproteinemia, severe proteinuria, accompanied with renal insufficiency persisted despite these therapies. We initiated hemodialysis on day 17, and LDL-A on day 18. After the treatment, we found an improvement in her urine protein excretion, hyperlipidemia, and hypoproteinemia gradually. Her renal function returned to normal. We added cyclosporine A (CyA) after confirming the normal renal function. Her proteinuria was 0.693 g/day on day 350 and she achieved incomplete remission type I. There are few reports of the efficacy of LDL-A in older patients with MCD with acute kidney injury (AKI). In addition, there are only a few reports of cases in which LDL-A was introduced early, as in this case. This case suggests that early LDL-A may be an effective therapy for steroid-resistant MCD with AKI.
2025-03-04 | Personalized disease recurrence modeling using iPSC-derived podocytes in patients with idiopathic nephrotic syndrome.
Primary focal segmental glomerulosclerosis (FSGS) is characterized by podocyte injury and treatment-resistant nephrotic syndrome. Recurrence of the original disease after kidney transplantation (rFSGS) occurs in 10%-50% of patients. Unidentified circulating permeability factors (CPF) are likely involved in FSGS pathogenesis. We hypothesized that donor podocyte susceptibility to CPF is also relevant. We developed a personalized model for (r)FSGS using induced pluripotent stem cell (iPSC)-derived podocytes from patients and kidney donors. Five patients and their respective living kidney donors were included. Three patients had developed rFSGS, and two patients manifested no symptoms of rFSGS. One patient (P5) had heterozygous mutations in NPHS2. Peripheral blood mononuclear cells were reprogrammed to iPSC, and differentiated to podocytes. iPSC-derived podocytes from either patients or donors were exposed to presumed CPF-containing plasma/serum of corresponding patients. Three assays to detect podocyte injury were performed: (i) reactive oxygen species formation, (ii) cellular granularity induction, and (iii) quantitative assessment of F-actin redistribution (FAR), a new quantitative method. Crossmatch experiments with donor iPSC-derived podocytes and patients samples assessed individual susceptibility to CPF-induced injury. Successful podocyte differentiation was confirmed by morphology and protein expression. Only FAR differentiated consistently between patient and healthy donor samples. All pre-transplant patient samples except P5 caused significant FAR in corresponding patient podocytes. Significant FAR was observed in donor podocytes exposed to corresponding patient samples in the setting of rFSGS, and not in donor podocytes exposed to samples of patients who did not develop rFSGS. Effects of FSGS patient samples on non-corresponding donor podocytes were variable. In vitro assays using iPSC-derived donor podocytes may allow individualized assessment of rFSGS. Prospective studies in a larger cohort are required to validate our findings.
other
2026-06-23 | Genetic Nephrotic Syndrome in Children and Adolescents: An Update.
Idiopathic nephrotic syndrome is one of the most common glomerular diseases in children and adolescents. Monogenic nephrotic syndrome is associated with lower rates of remission following treatment with standard immunosuppressive therapies and a higher risk of progression to end-stage kidney disease. Advances in genetic testing technologies have identified more than 100 single-gene causes of nephrotic syndrome and made genetic testing more accessible in clinical practice. The vast majority of genes implicated in the etiology of nephrotic syndrome are associated with the glomerular filtration barrier and primarily with the podocyte. A molecular diagnosis of nephrotic syndrome has implications for medication choice, prognostication, indications for further testing, and transplant planning. Like all clinical tools, however, it must be utilized in the appropriate clinical context, though no standardized guidelines exist for indications for genetic testing in nephrotic syndrome. Standard treatment of nephrotic syndrome consists of immunosuppressive therapies. However, patients with monogenic nephrotic syndrome are less likely to achieve remission with immunosuppression, and alternative treatment options are under investigation.
2025-12-27 | Nephrotic syndrome genomic discovery in the Mass General Brigham Biobank identifies monoallelic MEFV variants as a risk factor for focal segmental glomerulosclerosis.
Health system-based biobanks with genetic data provide a unique opportunity for nephrotic syndrome (NS) genomic discovery. This is predicated on finding cases in the electronic health record. We tested three strategies to identify focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD) cases in the 130,000 members of Mass General Brigham Biobank (MGBB). We analyzed a "synthetic proteinuria panel" of 192 Mendelian genes and the APOL1 kidney risk variants in those with exome sequencing (ES). We studied the associations between patients with Mendelian variants (MV), APOL1-HR genotype (APOL1) and outcomes. Validation of a novel gene-FSGS association was done in the Genomics England 100,000 Genome Project (100KG) and a global NS case-control cohort. 319 MGBB participants had FSGS or MCD and ES data; reviewing pathology reports was the most accurate screening strategy. 31 (9.7%) of patients had MV and 24 (7.5%) had APOL1. 61% of genetic NS with a kidney biopsy report were classified as secondary FSGS. MV and APOL1 patients had a 3.1 (1.1-8.7) and 6.5 (1.3-32.3) increased odds of developing kidney failure, respectively. Unexpectedly, monoallelic pathogenic variants in MEFV (Mendelian gene for Familial Mediterranean Fever [FMF]) were found in 6 MGBB participants with FSGS, all of whom had features of collapsing glomerulopathy and thrombotic microangiopathy. 8 glomerular disease cases in the 100KG, unsolved via genome sequencing, had monoallelic pathogenic MEFV variants. Finally, a case-control study found a 3.8 increased odds of SRNS in individuals with pathogenic or likely pathogenic MEFV alleles (P = 7.8 × 10-5). 17.2% of unselected adults with NS in the MGBB had a well-established genetic form, each associated with an increased risk of kidney failure. A biopsy read of secondary FSGS should not be used to rule out testing for genetic disease. Monoallelic pathogenic variants in MEFV may be a novel and underappreciated cause or susceptibility factor for SRNS/FSGS with distinct histologic features, even in the absence of clinical FMF.
2025-06-28 | The Efficacy of Pneumococcal and Influenza Vaccination in Prevention of Relapse of Steroid-Sensitive Nephrotic Syndrome in Children
Abstract Background: Nephrotic syndrome (NS) is a common disorder in the pediatric age group. The majority of them developed relapse due to infection. About 50%–70% relapses occur due to respiratory tract infection. Therefore, pneumococcal and influenza vaccination may prevent the number of relapses. Materials and Methods: This prospective, case–control study was carried out in the department of Pediatric Nephrology, Bangabandhu Sheikh Mujib Medical University, Dhaka, from November 2016 to February 2018. A total of 120 patients aged 2–18 years old with an initial episode of idiopathic NS (INS) were included in this study. They were divided in two groups according to age and administration of the Haemophilus influenzae vaccine: Group A and Group B. Group A included 60 children of younger age group (2–8 years). All of them received Haemophilus influenzae vaccine through the Expanded Program on Immunization (EPI) schedule. They were further subdivided into two subgroups: Group A1 and Group A2. Group A1 included 30 children who received pneumococcal and influenza vaccines. Group A2 also included 30 children who refused vaccination. Similarly, Group B included 60 children, and they belonged to the older age group (>8–18 years). They did not receive Haemophilus influenzae vaccine through the EPI schedule. They were further subdivided into two subgroups: Group B1 and Group B2. Group B1 included 30 children who received pneumococcal and influenza vaccine. Group B2 also included 30 children who refused vaccination. All of them were followed up for 1 year to compare the clinical effects. Results: A total of 120 patients were studied. Among them, the number of patients without relapses was high in the younger age vaccinated group than non-vaccinated group (36.7% vs. 10%; P = 0.003). In addition to this, older age vaccinated group developed less relapses compared to the non-vaccinated group ( P < 0.05). This indicates that vaccination has a beneficial role in preventing relapse in children with INS. Conclusion: Vaccination against pneumococcus and influenza lowers relapses in children with INS.
2025-05-22 | Association between SIRT-1 and SERPINA4 gene polymorphisms and the risk of idiopathic nephrotic syndrome among Egyptian children.
Idiopathic nephrotic syndrome (INS) is the primary cause of chronic glomerular dysfunction in children. Despite extensive research, its pathophysiology remains unclear, particularly in cases that are resistant to steroids. This research evaluated the impact of SIRT-1 (rs2273773) and SERPINA4 (rs2093266) gene variants on Egyptian children's susceptibility to INS and response to steroid therapy. Genetic polymorphisms of SIRT-1 (rs2273773) and SERPINA4 (rs2093266) were screened in 135 INS children and a similar number of healthy volunteers using real-time PCR. Concerning SIRT-1 rs2273773 genotypes, the cases showed markedly greater CT, TT genotypes, and T allele incidences than the reference group, which increased the risk of INS by 2.01-, 4.03-, and 1.88-folds, respectively. Regarding SERPINA4 rs2093266 genotypes, the cases exhibited notably higher GA, AA genotypes, and the A allele frequencies than controls, which enlarged the risk of INS by 3.1-, 5.47-, and 2.82-folds, respectively. The frequency of GA and AA genotypes and the presence of the A allele of SERPINA4 rs2093266 were considerably higher in steroid-resistant versus steroid-sensitive cases. The logistic regression model stated the serum creatinine, blood urea nitrogen, and the SERPINA4 rs2093266 polymorphism as independent contributors to the risk for steroid resistance in INS cases. SIRT-1 (rs2273773) and SERPINA4 (rs2093266) gene polymorphisms significantly attributed to the risk of developing INS in Egyptian children. Furthermore, the SERPINA4 (rs2093266) polymorphism has a strong correlation with steroid resistance, suggesting that it could be a target for treatment to avoid severe renal problems and adverse steroid effects.
2024-11-27 | NPHS Mutations in Pediatric Patients with Congenital and Steroid-Resistant Nephrotic Syndrome.
NPHS1 and NPHS2 are kidney gene components that encode for nephrin and podocin, respectively. They play a role in the progression of congenital (CNS) and steroid-resistant (SRNS) nephrotic syndrome. Hence, this study aimed to determine the prevalence and renal outcomes of NPHS mutations among pediatric patients with CNS and SRNS. We also aimed to identify potential predictors of NPHS mutations in this patient cohort. Overall, this study included 33 studies involving 2123 patients screened for NPHS1, whereas 2889 patients from 40 studies were screened for NPHS2 mutations. The patients' mean age was 4.9 ± 1 years (ranging from birth to 18 years), and 56% of patients were male (n = 1281). Using the random-effects model, the pooled proportion of NPHS1 mutations among pediatric patients with CNS and SRNS was 0.15 (95% CI 0.09; 0.24, p < 0.001, I2 = 92.0%). The pooled proportion of NPHS2 mutations was slightly lower, at 0.11 (95% CI 0.08; 0.14, p < 0.001, I2 = 73.8%). Among the 18 studies that reported ESRF, the pooled proportion was 0.47 (95% CI 0.34; 0.61, p < 0.001, I2 = 75.4%). Our study showed that the NPHS1 (β = 1.16, p = 0.35) and NPHS2 (β = 5.49, p = 0.08) mutations did not predict ESRF in CNS and SRNS pediatric patients. Nevertheless, patients from the European continent who had the NPHS2 mutation had a significantly higher risk of developing ESRF (p < 0.05, β = 1.3, OR = 7.97, 95% CI 0.30; 2.30) compared to those who had the NPHS1 mutation. We recommend NPHS mutation screening for earlier diagnosis and to avoid unnecessary steroid treatments. More data are needed to better understand the impact of NPHS mutations among pediatric patients with CNS and SRNS.
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Drug Discovery Landscape
2 orphan drug designations for Idiopathic nephrotic syndrome.
2 orphan drug designations for Idiopathic nephrotic syndrome.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Pioglitazone hydrochloride | small molecules | FDA | — | NephKey Therapeutics, Inc. |
Levamisol hydrochloride | small molecules | EMA | ACE Pharmaceuticals BV |
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