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Nephrotic syndrome (NS) is a clinical picture common to several diseases resulting from damage to podocytes and glomerular filtration barrier. Currently, there is limited consensus regarding the diagnostic pathway and management of the specific etiology. Some patients show complete response to first-line steroid therapy (steroid-sensitive nephrotic syndrome, SSNS), especially in children and young adults. The prognosis of this group is generally favorable. In contrast, patients unresponsive to steroids (steroid-resistant NS, SRNS) frequently undergo immunosuppressive therapies, which are burdened with numerous side effects. Resistance to treatment is associated with a high likelihood of progression to chronic renal disease (CKD) and kidney failure (ESKD). Recent evidence suggests that immunological mechanisms (including permeabilizing factors) are involved in the pathogenesis of post-transplant NS recurrence and SSNS.
Providing patients with NS with a correct diagnosis is the cornerstone of personalized medicine, reducing morbidity and side effects of therapies, ensuring their appropriate prescription, and slowing or preventing progression to ESKD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with SSNS | Experimental | Patients with SSNS and patients undergoing renal transplantation for NS with post-transplant disease recurrence will be enrolled for serum sampling for the study of immunological and/or permeabilizing factors (including anti-nephrin antibodies). |
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| Patients with SRNS undergoing genetic testing by WES | Experimental | Patients with SRNS undergoing genetic testing by WES and variant prioritization will undergo serum sampling for the study of immunologic and/or permeabilizing factors (including the anti-nephrin antibodies), and urine sampling for u-RPC cultures. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Anti-nephrin antibodies | Diagnostic Test | Assessment of anti-nephrin antibodies on serum samples and in vitro study of permeabilizing effect on 3D organ-on-a-chip models and STED microscopy on healthy human kidneys. |
| Measure | Description | Time Frame |
|---|---|---|
| Role of anti-nephrin antibodies in the pathogenesis of NS | The presence of circulating permeabilizing factors, including anti-nephrin antibodies, will be evaluated in serum samples of patients with NS and/or kidney transplant recipients with NS recurrence. The results will be correlated with the clinical history of disease in order to understand the disease pathomechanisms and the risk of recurrence. | From enrollment until the last patient visit (up to 12 months from enrollment) |
| Measure | Description | Time Frame |
|---|---|---|
| Functional role of VUS in the pathogenesis of SRNS | The functional role of VUS identified by WES will be assessed by in vitro studies on u-RPCs and 3D organ-on-a-chip models. The results will be expressed as diagnostic rate, i.e., number of conclusive diagnosis allowed by functional studies of VUS/number of patients enrolled in the study. | From enrollment until the last patient last visit (up to 12 months from enrollment) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Paola Romagnani, Prof, MD, PhD | Contact | 055 5662562 | paola.romagnani@meyer.it |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Meyer Children's Hospital IRCCS | Recruiting | Florence | Italy |
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| ID | Term |
|---|---|
| D009404 | Nephrotic Syndrome |
| ID | Term |
|---|---|
| D009401 | Nephrosis |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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Patients with nephrotic syndrome (SSNS, SRNS)
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| u-RPC cultures | Diagnostic Test | Urine sample collection for u-RPC cultures |
|
| Identification of potential predictive biomarkers of renal outcome. | The identification of potential biomarkers of disease progression and kidney failure will be performed by gene expression by scRNA-seq of u-RPCs. The results will be correlated to clinical data. | From enrollment until the last patient visit (up to 12 months from enrollment) |
| Cost-effectiveness analysis | A modeled cost-effectiveness analysis (including direct and indirect medical costs) will be performed to compare the proposed diagnostic algorithm with the current standard-of-care. | From enrollment of the last patient until the last visit (up to 12 months from enrollment) |
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |