Biomarkers and Outcome Predictors of Pediatric Nephrotic Syndrome: A Genetic, Transcriptomic, and Secretome Multiomics Study

NCT06792448 | Not Yet Recruiting

• 2 other identifiers: 5244_11.09.2024_PEJPRD23-108
• Study Type: observational
• Target: 350
• Locations: 0 countries
• Sites: N/A

Brief Summary

Idiopathic Nephrotic Syndrome is a rare disease of the kidneys, which typically affects children. For most affected children there is the need of a prolonged treatment with drugs reducing the activity of the immune system, also resulting in many side effects. Those patients, who do not respond to treatment, are at risk of kidney damage and of dialysis or kidney transplantation. It is currently impossible to predict the response to treatment, leading to unnecessary therapies with side effects as well as unclear prognosis in the affected children. The response of the idiopathic nephrotic syndrome to medications acting on the immune system explains its important role in the occurrence of the disease. With this study we aim to obtain predictors of the response to treatment right at the beginning of the disease, to adapt the therapy avoiding needless side effects. This will be done evaluating the blood and urine of affected children using state of the art molecular characterisation. We will evaluate the genetic predisposition, the cell trait changes and the presence of molecules in blood and urine that may affect the interaction between the immune system and the kidneys. We expect that the findings will improve treatment of children with idiopathic nephrotic syndrome and reduce the number of children suffering from unnecessary drugs related side effects.

Conditions

Nephrotic Syndrome Steroid-Dependent; Nephrotic Syndrome Steroid-Resistant; Nephrotic Syndrome in Children; Glomerulonephritis; Proteinuria; Hypoalbuminemia; Kidney Diseases; Chronic Kidney Disease

Keywords

Pediatric nephrotic syndrome; Idiopathic nephrotic syndrome; Steroid-resistant nephrotic syndrome; Steroid-sensitive nephrotic syndrome; Biomarkers discovery; Genetic risk factors; Epigenetic analysis; Adaptive immune system profiling; Liquid biopsy; Serum and urine proteomics; Multiomics approach; Personalized treatment; Disease progression prediction; Molecular characterization; Pediatric kidney disease

Outcome Measures

Primary Outcomes (1)

• Predictive Molecular Signature of INS Progression

  Identification of distinct molecular characteristics predictive of the progression of idiopathic nephrotic syndrome (INS). This includes differentiating between steroid-resistant nephrotic syndrome (SRNS), steroid-dependent nephrotic syndrome (SDNS), and infrequent relapsing nephrotic syndrome (IRNS). Measure Type: Analysis of genetic/epigenetic background, immune status, and vesicular proteome/transcriptomic profile. Goal: Develop a biomarker-based predictive model that assists in early classification of INS subtypes.

  Up to 1 year from enrollment after initial diagnosis.

Secondary Outcomes (4)

• Genetic and Epigenetic Risk Factors

  Up to 6 months from enrollment after initial diagnosis.

• Immune System Alterations

  Up to 1 year from enrollment after initial diagnosis.

• Proteomic Patterns in Serum and Urine

  Up to 1 year from enrollment after initial diagnosis.

• Molecular Profile of Healthy Control Group

  At a single time point during enrollment.

Study Arms (3)

Treatment-Naive Idiopathic Nephrotic Syndrome (INS) Patients

This cohort comprises 110 children diagnosed with idiopathic nephrotic syndrome (INS) who are treatment-naive at enrollment. The participants will receive a standard induction therapy with prednisone or prednisolone and will be followed for 12 months. During this period, blood and urine samples will be collected at various points (enrollment, 6 weeks, 6 months, and 12 months) and in cases of relapse. The goal is to monitor disease progression and classify patients based on their response to therapy, specifically identifying subtypes such as steroid-resistant, steroid-dependent, and infrequent relapsing nephrotic syndrome .

Healthy Pediatric Control Group

This cohort consists of 40 age-matched children without nephrotic syndrome, selected from individuals undergoing minor urological surgical procedures. These participants will provide baseline control samples (blood and urine) for comparison with the INS patients' samples. This group allows researchers to identify molecular characteristics unique to INS by contrasting them with data from healthy children .

Prevalent Idiopathic Nephrotic Syndrome (INS) Patients

This group includes 200 INS patients who have previously received treatment and are part of the larger validation phase. This cohort will be used to confirm the biomarkers and molecular profiles identified in the main cohort. The aim is to generalize findings and ensure that identified biomarkers are consistent across a broader population. Samples will be collected during relapse and remission, aligning with the study's focus on validating predictive biomarkers of disease course and therapeutic response .

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The study participants will be selected from a population of pediatric patients with idiopathic nephrotic syndrome (INS) who are treatment-naive and present with clinical symptoms such as proteinuria, hypoalbuminemia, and edema. These patients, aged 1 to 18 years, are typically referred to specialized nephrology clinics or tertiary care centers across Europe, where they receive initial diagnosis and follow-up care. The participant pool is drawn from both primary recruiting centers, which are large pediatric nephrology units with established expertise in managing nephrotic syndrome, and additional collaborating centers within the European ERKNet and ESCAPE Networks. This setting ensures a broad representation of pediatric INS cases across various European regions, enhancing the study's generalizability. Additionally, a control group of age-matched children without nephrotic syndrome is included, selected from children undergoing minor urological procedures in these clinical settings.

You may qualify if:

• Clinical diagnosis of idiopathic nephrotic syndrome (INS) with nephrotic range proteinuria (uPr/uCr ratio \> 2 mg/mg).
• Hypoalbuminemia with serum albumin \< 3.0 g/dL.
• Presence of edema.
• No prior treatment for idiopathic nephrotic syndrome.
• Age between 1 and 18 years at the time of enrollment.
• igned informed consent by a parent or legal guardian.

You may not qualify if:

• Diagnosis of congenital or infantile nephrotic syndrome (age \< 1 year).
• Diagnosis of secondary nephrotic syndrome.
• Presence of glomerulonephritis, autoimmune diseases, or vasculitis.
• Lack of signed informed consent by a parent or legal guardian.
• Previous treatment with prednisone or prednisolone for nephrotic syndrome.

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead
• Fondazione La Nuova Speranza ONLUS: collaborator
• ASSOCIAZIONE SINDROME NEFROSICA ITALIA: collaborator
• Nephie e.V.: collaborator
• NephCEurope: collaborator
• European Joint Programme on Rare Diseases (EJP RD JTC 2023): collaborator
• ERKNet: collaborator

Biospecimen

Retention: SAMPLES WITH DNA

1. Blood samples: Collected for genetic analysis. Used for peripheral blood mononuclear cells (PBMC) extraction. 2. Urine samples: Collected for molecular analysis. Used to evaluate protein/creatinine ratios and perform urinalysis. 3. Serum samples: Collected for molecular analysis. These samples are collected at various stages according to the study's protocol, including onset, relapse, and remission, for use in multiomic analyses to identify molecular predictors of disease progression and treatment response

MeSH Terms

Conditions

Nephrotic Syndrome; Glomerulonephritis; Proteinuria; Hypoalbuminemia; Kidney Diseases; Renal Insufficiency, Chronic; Nephrosis, Lipoid

Condition Hierarchy (Ancestors)

Nephrosis; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Nephritis; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hypoproteinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes

Study Officials

• Giovanni Montini, Doctor of Medicine

  Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Federica Lugani, Doctor of Medicine

CONTACT

+39 02 5503 3434; federica.lugani@policlinico.mi.it

William Morello, Doctor of Medicine

CONTACT

+39 02 5503 3434; william.morello@policlinico.mi.it

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2024
• First Posted: January 24, 2025
• Study Start: February 15, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: January 30, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share