RARE DISEASE
Idiopathic steroid-sensitive nephrotic syndrome
Idiopathic steroid-sensitive nephrotic syndrome
Idiopathic steroid-sensitive nephrotic syndrome
Drug discovery
2
drugs
With orphan designations
Overview
Idiopathic steroid-sensitive nephrotic syndrome (SSNS) is a pediatric-onset glomerular disorder characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. It typically responds to initial corticosteroid therapy but exhibits relapses in 40-60% of cases, often requiring steroid-sparing immunosuppressants. While renal prognosis is generally favorable, long-term morbidity arises from treatment side effects and relapses [1][3][6][17].
Burden
30-50% experience frequent relapses, leading to high cumulative steroid exposure with risks of obesity, growth impairment, and osteoporosis [9][11].
Significant caregiver psychological distress (17-31%) and healthcare utilization during relapses [9][16].
~15% develop secondary steroid resistance in adulthood, increasing chronic kidney disease risk [4][12].
Categories: rare renal diseases, rare transplant-related disorders
Research Papers
611 drug discovery papers related to Idiopathic steroid-sensitive nephrotic syndrome, with 3 first-in-class and 4 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
611 drug discovery papers related to Idiopathic steroid-sensitive nephrotic syndrome, with 3 first-in-class and 4 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-06 | Expression of PD-1 on T cells and its predictive value for steroid resistance in children with idiopathic nephrotic syndrome.
Programmed cell death protein 1 (PD-1) plays a pivotal role in regulating T-cell responses. Its expression profile and clinical significance in pediatric idiopathic nephrotic syndrome (INS), particularly in steroid-resistant nephrotic syndrome (SRNS), remain unclear. PD-1 expression on CD3⁺, CD4⁺, and CD8⁺T cells was quantified by flow cytometry in 65 treatment-naive children with idiopathic nephrotic syndrome (INS): steroid-sensitive (SSNS, n = 54), steroid-resistant (SRNS, n = 11), as well as in healthy controls (HC, n = 30). Group differences, clinical correlations and PD-1's predictive value for SRNS were analyzed. Circulating T subsets, including CD3⁺PD-1⁺ T cells, CD4⁺PD-1⁺T cells, and CD8⁺PD-1⁺T were detected with multiparameter flow cytometry. The percentage of CD4⁺PD-1⁺ T cells was significantly higher in SRNS (10.77 ± 4.62%) compared to both SSNS (5.14 ± 1.99%, P = 0.000) and HC (6.36 ± 2.02%, P = 0.028). CD3⁺PD-1⁺ T cells were also elevated in SRNS (8.13 ± 3.12%) versus SSNS (4.67 ± 1.82%, P = 0.001). No significant difference was found in CD8⁺PD-1⁺ T cells. Multivariate logistic regression identified an elevated percentage of CD4⁺PD-1⁺ T cells as an independent risk factor for SRNS (OR = 2.236, P = 0.002). Receiver operating characteristic (ROC) analysis showed that CD4⁺PD-1⁺ T cell cutoff > 7.385% predicted SRNS with an area under the curve (AUC) of 0.891, sensitivity of 81.8%, and specificity of 87.0%. Overexpression of PD-1, predominantly on CD4⁺ T cells, is associated with steroid resistance in pediatric INS. Elevated CD4⁺PD-1⁺ T cells may serve as a predictive biomarker for SRNS, offering a potential tool for early identification and a rationale for exploring PD-1 pathway modulation.
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.
2026-06-19 | 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.
2026-07-06 | Expression of PD-1 on T cells and its predictive value for steroid resistance in children with idiopathic nephrotic syndrome.
Programmed cell death protein 1 (PD-1) plays a pivotal role in regulating T-cell responses. Its expression profile and clinical significance in pediatric idiopathic nephrotic syndrome (INS), particularly in steroid-resistant nephrotic syndrome (SRNS), remain unclear. PD-1 expression on CD3⁺, CD4⁺, and CD8⁺T cells was quantified by flow cytometry in 65 treatment-naive children with idiopathic nephrotic syndrome (INS): steroid-sensitive (SSNS, n = 54), steroid-resistant (SRNS, n = 11), as well as in healthy controls (HC, n = 30). Group differences, clinical correlations and PD-1's predictive value for SRNS were analyzed. Circulating T subsets, including CD3⁺PD-1⁺ T cells, CD4⁺PD-1⁺T cells, and CD8⁺PD-1⁺T were detected with multiparameter flow cytometry. The percentage of CD4⁺PD-1⁺ T cells was significantly higher in SRNS (10.77 ± 4.62%) compared to both SSNS (5.14 ± 1.99%, P = 0.000) and HC (6.36 ± 2.02%, P = 0.028). CD3⁺PD-1⁺ T cells were also elevated in SRNS (8.13 ± 3.12%) versus SSNS (4.67 ± 1.82%, P = 0.001). No significant difference was found in CD8⁺PD-1⁺ T cells. Multivariate logistic regression identified an elevated percentage of CD4⁺PD-1⁺ T cells as an independent risk factor for SRNS (OR = 2.236, P = 0.002). Receiver operating characteristic (ROC) analysis showed that CD4⁺PD-1⁺ T cell cutoff > 7.385% predicted SRNS with an area under the curve (AUC) of 0.891, sensitivity of 81.8%, and specificity of 87.0%. Overexpression of PD-1, predominantly on CD4⁺ T cells, is associated with steroid resistance in pediatric INS. Elevated CD4⁺PD-1⁺ T cells may serve as a predictive biomarker for SRNS, offering a potential tool for early identification and a rationale for exploring PD-1 pathway modulation.
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.
2026-06-19 | 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.
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles and probability of success in trials forecasts:
Drug Discovery Landscape
2 orphan drug designations for Idiopathic steroid-sensitive nephrotic syndrome.
2 orphan drug designations for Idiopathic steroid-sensitive nephrotic syndrome.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
obinutuzumab | antibodies | FDA | 2021-11-22 | — | Genentech, Inc. |
Atrasentan | small molecules | FDA | 2016-09-29 | — | AbbVie Inc. |
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