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
1,596 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:
1,596 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:
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.
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.
2026-07-08 | Obinutuzumab as a primary anti-CD20 agent in pediatric frequently relapsing and steroid-dependent nephrotic syndrome.
Idiopathic nephrotic syndrome (INS) is the leading glomerular disease in children, often responding well to steroids. However, frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS) require the introduction of steroid-sparing agents to mitigate steroid toxicity. This retrospective, pilot study including 6 patients with FRNS or SDNS assessed the efficacy and safety of obinutuzumab as a first line of anti-CD20 therapy. Using one dose of obinutuzumab, complete remission was achieved in all 6 patients within 11 months. Remission rate was 100% up to 12 months post-injection, and 80% at both 24 and 56 months. Infusion-related reactions occurred in 83% of the patients, primarily mild and transient; one patient required immunoglobulin supplementation but no severe infections were noted. These preliminary results suggest that obinutuzumab is a promising first-line anti-CD20 therapy for FRNS and SDNS in children, offering sustained remission with a good safety profile.
2026-07-06 | Use of rituximab and mycophenolate in cortic-dependent nephrotic syndrome in pediatrics
introduction: Idiopathic nephrotic syndrome (INS) in children may present frequent relapses or steroid dependence, with a risk of corticosteroid toxicity.In this context, rituximab (RTX) and mycophenolate mofetil (MMF) were used as alternative therapeutic options.Materials and methods: A prospective observational cohort study was conducted in a pediatric nephrology unit in the Autonomous City of Buenos Aires, including 12 patients with steroid-dependent nephrotic syndrome (SDNS) who received sequential treatment with RTX and MMF.results: Of the 12 patients treated with RTX, 4 achieved sustained remission.The remaining 8 had fewer than 2 relapses per year but required potentially toxic steroid doses; therefore, after a mean period of 13 months post-RTX, MMF was added.All patients remained in remission until the end of the study.The cumulative steroid dose (CSD) pre-RTX was 5335 mg/m 2 and post-RTX was 2024 mg/m 2 (p = 0.001).Finally, the mean CSD with MMF was 1378 mg/m 2 (Wilcoxon test: T = 3.5, p = 0.005).In the 10 patients who experienced at least one relapse, the mean CD20 lymphocyte count one month after RTX was 3.7 cells/mm 3 , and at relapse it was 26 cells/mm 3 (CD20-proteinuria correlation coefficient: 0.54).Observed adverse effects were minimal and reversible.conclusion: Sequential therapy with RTX and MMF may be an option for patients with primary steroid-dependent nephrotic syndrome.
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.
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.
2026-07-08 | Obinutuzumab as a primary anti-CD20 agent in pediatric frequently relapsing and steroid-dependent nephrotic syndrome.
Idiopathic nephrotic syndrome (INS) is the leading glomerular disease in children, often responding well to steroids. However, frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS) require the introduction of steroid-sparing agents to mitigate steroid toxicity. This retrospective, pilot study including 6 patients with FRNS or SDNS assessed the efficacy and safety of obinutuzumab as a first line of anti-CD20 therapy. Using one dose of obinutuzumab, complete remission was achieved in all 6 patients within 11 months. Remission rate was 100% up to 12 months post-injection, and 80% at both 24 and 56 months. Infusion-related reactions occurred in 83% of the patients, primarily mild and transient; one patient required immunoglobulin supplementation but no severe infections were noted. These preliminary results suggest that obinutuzumab is a promising first-line anti-CD20 therapy for FRNS and SDNS in children, offering sustained remission with a good safety profile.
2026-07-06 | Use of rituximab and mycophenolate in cortic-dependent nephrotic syndrome in pediatrics
introduction: Idiopathic nephrotic syndrome (INS) in children may present frequent relapses or steroid dependence, with a risk of corticosteroid toxicity.In this context, rituximab (RTX) and mycophenolate mofetil (MMF) were used as alternative therapeutic options.Materials and methods: A prospective observational cohort study was conducted in a pediatric nephrology unit in the Autonomous City of Buenos Aires, including 12 patients with steroid-dependent nephrotic syndrome (SDNS) who received sequential treatment with RTX and MMF.results: Of the 12 patients treated with RTX, 4 achieved sustained remission.The remaining 8 had fewer than 2 relapses per year but required potentially toxic steroid doses; therefore, after a mean period of 13 months post-RTX, MMF was added.All patients remained in remission until the end of the study.The cumulative steroid dose (CSD) pre-RTX was 5335 mg/m 2 and post-RTX was 2024 mg/m 2 (p = 0.001).Finally, the mean CSD with MMF was 1378 mg/m 2 (Wilcoxon test: T = 3.5, p = 0.005).In the 10 patients who experienced at least one relapse, the mean CD20 lymphocyte count one month after RTX was 3.7 cells/mm 3 , and at relapse it was 26 cells/mm 3 (CD20-proteinuria correlation coefficient: 0.54).Observed adverse effects were minimal and reversible.conclusion: Sequential therapy with RTX and MMF may be an option for patients with primary steroid-dependent nephrotic syndrome.
Access all drug discovery papers and probability of success in trials forecasts:
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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 | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Pioglitazone hydrochloride | small molecules | FDA | 2022-07-20 | — | NephKey Therapeutics, Inc. |
Levamisol hydrochloride | small molecules | EMA | 2005-10-28 | — | ACE Pharmaceuticals BV |
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