Implementation of a Diagnostic Workflow for Personalized Diagnosis of Nephrotic Syndrome

Nephrotic Syndrome Clinical Trial

Official title:

Implementation of a Diagnostic Workflow for Personalized Diagnosis of Nephrotic Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06325098
• Other study ID #: PER-NEPH
• Status: Recruiting
• Phase: N/A
• Start date: January 26, 2022
• Est. completion date: June 30, 2026

Study information

• Verified date: March 2024
• Source: Meyer Children's Hospital IRCCS
• Contact: Paola Romagnani, Prof, MD, PhD
• Phone: 055 5662562
• Email: paola.romagnani[@]meyer.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: June 30, 2026
• Est. primary completion date: January 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Nephrosis
• Nephrotic Syndrome
• Syndrome

Intervention

Diagnostic Test:
• Anti-nephrin antibodies
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.
• u-RPC cultures
Urine sample collection for u-RPC cultures

Locations

Country	Name	City	State
Italy	Meyer Children's Hospital IRCCS	Firenze

Sponsors (1)

Lead Sponsor	Collaborator
Meyer Children's Hospital IRCCS

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Secondary	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)
Secondary	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)
Secondary	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)