Implementation of a Diagnostic Workflow for Personalized Diagnosis of Nephrotic Syndrome

Not Applicable

Recruiting

• Conditions: Nephrotic Syndrome
• Interventions: Diagnostic Test: Anti-nephrin antibodies; Diagnostic Test: u-RPC cultures

• Registration Number: NCT06325098
• Lead Sponsor: Meyer Children's Hospital IRCCS

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-01-26
• Status Verified: 2024-03
• Study First Submitted: 2024-03-01
• Study First Submitted QC: 2024-03-15
• Last Update Submitted: 2024-03-15
• Study First Posted: 2024-03-22
• Last Update Posted: 2024-03-22
• Primary Completion: 2026-01-31
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• Clinical diagnosis of NS (SSNS, SRNS, or NS relapsed after transplantation regardless of initial response to steroid therapy)
• Age below 40 years at disease onset
• Availability of clinical information
• Signed informed consent form

Exclusion Criteria

• Age at onset above 40 years
• Kidney biopsy proving lesions other than FSGS and MCD

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients with SRNS undergoing genetic testing by WES	Anti-nephrin antibodies	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.
Patients with SSNS	Anti-nephrin antibodies	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).
Patients with SRNS undergoing genetic testing by WES	u-RPC cultures	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.

Primary Outcome Measures

Name	Time	Method
Role of anti-nephrin antibodies in the pathogenesis of NS	From enrollment until the last patient visit (up to 12 months from enrollment)	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.

Secondary Outcome Measures

Name	Time	Method
Cost-effectiveness analysis	From enrollment of the last patient until the last visit (up to 12 months from enrollment)	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.
Identification of potential predictive biomarkers of renal outcome.	From enrollment until the last patient visit (up to 12 months from enrollment)	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.
Functional role of VUS in the pathogenesis of SRNS	From enrollment until the last patient last visit (up to 12 months from enrollment)	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.

Trial Locations

Locations (1)

Meyer Children's Hospital IRCCS; 🇮🇹 Firenze, Italy