Implementation of a Diagnostic Workflow for Personalized Diagnosis of Nephrotic Syndrome

NCT06325098 | Recruiting

• 1 other identifier: PER-NEPH
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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.

Conditions

Nephrotic Syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Functional role of VUS in the pathogenesis of SRNS

  From enrollment until the last patient last visit (up to 12 months from enrollment)

• Identification of potential predictive biomarkers of renal outcome.

  From enrollment until the last patient visit (up to 12 months from enrollment)

• Cost-effectiveness analysis

  From enrollment of the last patient until the last visit (up to 12 months from enrollment)

Study Arms (2)

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).

Diagnostic Test: Anti-nephrin antibodies

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.

Diagnostic Test: Anti-nephrin antibodies; Diagnostic Test: u-RPC cultures

Interventions

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.

Patients with SRNS undergoing genetic testing by WES; Patients with SSNS

u-RPC cultures DIAGNOSTIC_TEST

Urine sample collection for u-RPC cultures

Patients with SRNS undergoing genetic testing by WES

Eligibility Criteria

• Age: 1 Month - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Meyer Children's Hospital IRCCS: lead

Study Sites (1)

Meyer Children's Hospital IRCCS

Florence, Italy

RECRUITING

MeSH Terms

Conditions

Nephrotic Syndrome

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Central Study Contacts

Paola Romagnani, Prof, MD, PhD

CONTACT

055 5662562; paola.romagnani@meyer.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD, PhD

Model Details: Patients with nephrotic syndrome (SSNS, SRNS)

Study Record Dates

• First Submitted: March 1, 2024
• First Posted: March 22, 2024
• Study Start: January 26, 2022
• Primary Completion: January 31, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 22, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)