Transcriptome Analysis in Idiopathic Nephrotic Syndrome: Steroid Responsiveness

NCT ID: NCT06325137

Last Updated: 2024-03-22

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-03-16
• Study Completion Date: 2025-03-31

Brief Summary

Idiopathic nephrotic syndrome (INS) affects the glomerular barrier by damaging the podocytes with foot process effacement, leading to a pathological increase of permeability and protein loss. INS classification is based on the clinical response to glucocorticoid (GC) therapy. When GCs treatment fails to induce remission in a four-six weeks course, patients are defined as affected with steroid-resistant nephrotic syndrome (SRNS).

The whole transcriptome sequencing could consent the INS classification at onset, prior to glucocorticoids (GCs) treatment, allowing to reduction of unuseful GCs treatment. RNA sequencing technologies allow an extensive characterization of the transcriptomic profile and permit global changes in gene expression levels between different conditions such as active and remission of the disease.

Of great interest is the research of a molecular biomarker to predict steroid resistance, a predictor that is not yet available. Among the candidate biomarkers, pharmacogenomic determinants are promising, even if available studies are still limited. Among these, some epigenetic factors have been previously suggested. Data obtained in animal models suggests that nucleotide-binding oligomerization domain-like receptors (NOD-like receptor) pyrin domain containing 3 (NLRP3) inflammasome can be deregulated in a wide variety of glomerular diseases, including those causing INS. Another potential marker involved in steroid response is the long noncoding RNA GAS5. Data reported in the literature indicate that abnormal levels of GAS5 in peripheral blood mononuclear cells (PBMCs) may alter steroid effectiveness in autoimmune diseases, such as inflammatory bowel disease.

Preliminary findings show that the study of NLRP3 promoter methylation could be reduced in the blood of SRNS compared with steroid-sensitive nephrotic syndrome (SSNS) patients. Moreover, unpublished encouraging results on the association between Growth Arrest Specific 5 (GAS5) expression and steroid response in INS in PBMCs were obtained in a preliminary study conducted on 8 patients with the first episode of INS. PBMCs were obtained and GAS5 gene expression was evaluated using TaqMan technology. Patients affected with SRNS presented significantly higher levels of GAS5 in comparison with the SSNS group. In PBMCs from SRNS patients, the GAS5 expression could reduce the availability for binding to GCs target genes of the activated GCs receptor and suppresses GC transcriptional activity.

Conditions

Nephrotic Syndrome

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Patients with steroid-resistant nephrotic syndrome

Identification of a possible molecular signatures at t0 by whole transcriptome analysis from PBMCs

Transcriptome analyses

Intervention Type: DIAGNOSTIC_TEST

A sample of peripheral whole blood cells will be collected at the onset before the initiation of steroid treatment (time 0, t0) and after 6 weeks at the definition of steroid sensitivity/unresponsiveness (time 1, t1).

Patients with steroid sensitive nephrotic syndrome

Identification of a possible molecular signatures at t0 by whole transcriptome analysis from PBMCs

Transcriptome analyses

Intervention Type: DIAGNOSTIC_TEST

A sample of peripheral whole blood cells will be collected at the onset before the initiation of steroid treatment (time 0, t0) and after 6 weeks at the definition of steroid sensitivity/unresponsiveness (time 1, t1).

Interventions

Transcriptome analyses

A sample of peripheral whole blood cells will be collected at the onset before the initiation of steroid treatment (time 0, t0) and after 6 weeks at the definition of steroid sensitivity/unresponsiveness (time 1, t1).

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• clinical diagnosis of INS
• age 1 - 12 years
• signed informed consent by parents or legal guardians
• For controls: aged-matched individuals with Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)

Exclusion Criteria

• Patients aged <1 year or > 12 years
• Patients diagnosed with a secondary or genetic form of NS
• For controls: the presence of coexisting chronic kidney failure, autoimmune or autoinflammatory disease, or endocrinologic disorders.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IRCCS Burlo Garofolo

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Institute for Maternal and Child Health - IRCCS "Burlo Garofolo"

Trieste, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Marco Pennesi, MD

Role: CONTACT

marco.pennesi@burlo.trieste.it

+39. 040-3785263

Barbara Bonifacio

Role: CONTACT

barbara.bonifacio@burlo.trieste.it

+39.040.3785.422

Facility Contacts

Marco Pennesi, MD

Role: primary

marco.pennesi@burlo.trieste.it

+39.040-3785263

Barbara Bonifacio

Role: backup

barbara.bonifacio@burlo.trieste.it

+39.040.3785.422

Other Identifiers

RC 24/2022

Identifier Type: -

Identifier Source: org_study_id