Autoantibodies Against-nephrin in Idiopathic Nephrotic Syndrome

NCT06334692 | Recruiting

• 1 other identifier: BLINDER
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This retrospective study is aimed at evaluating the levels of circulating anti-nephrin autoantibodies in patients with INS, including those with MCD/FSGS and in patients who have experienced relapse of FSGS post-transplant, compared to those of a control group of patients with nephrotic syndrome due to primary membranous nephropathy (MN).

Conditions

Nephrotic Syndrome

Keywords

Idiopathic nephrotic syndrome; Minimal change disease; Focal segmental glomerulosclerosis; Permeability factor(s); B cells; Nephrin autoantibodies

Outcome Measures

Primary Outcomes (1)

• Levels of circulating anti-nephrin autoantibodies

  Serum samples will be tested for the levels of anti-nephrin autoantibodies by in-house ELISA and results confirmed by commercial ELISA kits.

  At 1 year. Given the retrospective nature of the study, the indicated time frame refers to the time required to perform the analysis, i.e to assess levels of anti-nephrin antibodies in patients with NS compared to controls.

Study Arms (2)

Cases

Sera from patients with biopsy-proven idiopathic MCD or FSGS who provided consent to store their samples in the certified biobank (Mario Negri Biological Resources Centre - Rare Diseases and Renal Diseases Biobank - CRB). Serum samples will be tested for the levels of anti-nephrin autoantibodies by in-house ELISA and results confirmed by commercial ELISA kits.

Diagnostic Test: In-house ELISA, and ELISA kits from "DBA Italy" (Abbexa).

Controls

Sera from patients with biopsy-proven idiopathic membranous nephropathy who provided consent to store their samples in the certified biobank (Mario Negri Biological Resources Centre - Rare Diseases and Renal Diseases Biobank - CRB). Samples will be tested for the levels of anti-nephrin autoantibodies by in-house ELISA and results confirmed by commercial ELISA kits.

Diagnostic Test: In-house ELISA, and ELISA kits from "DBA Italy" (Abbexa).

Interventions

In-house ELISA, and ELISA kits from "DBA Italy" (Abbexa). DIAGNOSTIC_TEST

"Nunc MaxiSorp" ELISA plates will be coated with recombinant extracellular domain of human nephrin. Patient serum samples will be added in appropriate dilution. Plates will be then incubated with biotin-conjugated anti human IgG antibody followed by incubation with horseradish peroxidase (HRP)-avidin conjugate. Then tetramethylbenzidine substrate will be added, and absorbance read at 450 nm.

Cases; Controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

For the measurement of anti-nephrin antibodies, serum samples stored at the certified Biobank of Rare Diseases and Kidney Diseases of the Mario Negri Pharmacological Research Institute IRCCS from patients with INS (MCD/FSGS) and MN who provided their consent to the conservation of biological samples for future research projects evaluated and authorized by an independent Ethics Committee will be selected.

You may qualify if:

• Adult (\>18 years) males and females
• Patients with biopsy-proven idiopathic MCD or FSGS (cases)
• Patients with biopsy-proven idiopathic membranous nephropathy (controls)
• Patients who provided consent to store their samples in the certified CRB biobank

You may not qualify if:

• Reasonable possibility of a secondary cause of NS (for cases) or MN (for controls) at time of blood collections
• Active viral or bacterial infections at time of blood collections

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (1)

Clinical Research Center for Rare Disease Aldo e Cele Daccò

Ranica, BG, 24020, Italy

RECRUITING

Related Publications (9)

• McCarthy ET, Sharma M, Savin VJ. Circulating permeability factors in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2010 Nov;5(11):2115-21. doi: 10.2215/CJN.03800609. Epub 2010 Oct 21.

  PMID: 20966123 BACKGROUND

• D'Agati VD, Kaskel FJ, Falk RJ. Focal segmental glomerulosclerosis. N Engl J Med. 2011 Dec 22;365(25):2398-411. doi: 10.1056/NEJMra1106556. No abstract available.

  PMID: 22187987 BACKGROUND

• Gallon L, Leventhal J, Skaro A, Kanwar Y, Alvarado A. Resolution of recurrent focal segmental glomerulosclerosis after retransplantation. N Engl J Med. 2012 Apr 26;366(17):1648-9. doi: 10.1056/NEJMc1202500. No abstract available.

  PMID: 22533598 BACKGROUND

• Ruggenenti P, Ruggiero B, Cravedi P, Vivarelli M, Massella L, Marasa M, Chianca A, Rubis N, Ene-Iordache B, Rudnicki M, Pollastro RM, Capasso G, Pisani A, Pennesi M, Emma F, Remuzzi G; Rituximab in Nephrotic Syndrome of Steroid-Dependent or Frequently Relapsing Minimal Change Disease Or Focal Segmental Glomerulosclerosis (NEMO) Study Group. Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. J Am Soc Nephrol. 2014 Apr;25(4):850-63. doi: 10.1681/ASN.2013030251. Epub 2014 Jan 30.

  PMID: 24480824 BACKGROUND

• Maas RJ, Deegens JK, Smeets B, Moeller MJ, Wetzels JF. Minimal change disease and idiopathic FSGS: manifestations of the same disease. Nat Rev Nephrol. 2016 Dec;12(12):768-776. doi: 10.1038/nrneph.2016.147. Epub 2016 Oct 17.

  PMID: 27748392 BACKGROUND

• Watts AJB, Keller KH, Lerner G, Rosales I, Collins AB, Sekulic M, Waikar SS, Chandraker A, Riella LV, Alexander MP, Troost JP, Chen J, Fermin D, Yee JL, Sampson MG, Beck LH Jr, Henderson JM, Greka A, Rennke HG, Weins A. Discovery of Autoantibodies Targeting Nephrin in Minimal Change Disease Supports a Novel Autoimmune Etiology. J Am Soc Nephrol. 2022 Jan;33(1):238-252. doi: 10.1681/ASN.2021060794. Epub 2021 Nov 3.

  PMID: 34732507 BACKGROUND

• Casiraghi F, Todeschini M, Podesta MA, Mister M, Ruggiero B, Trillini M, Carrara C, Diadei O, Villa A, Benigni A, Remuzzi G. Immunophenotypic Alterations in Adult Patients with Steroid-Dependent and Frequently Relapsing Nephrotic Syndrome. Int J Mol Sci. 2023 Apr 22;24(9):7687. doi: 10.3390/ijms24097687.

  PMID: 37175393 BACKGROUND

• Salfi G, Casiraghi F, Remuzzi G. Current understanding of the molecular mechanisms of circulating permeability factor in focal segmental glomerulosclerosis. Front Immunol. 2023 Sep 19;14:1247606. doi: 10.3389/fimmu.2023.1247606. eCollection 2023.

  PMID: 37795085 BACKGROUND

• Shirai Y, Miura K, Ishizuka K, Ando T, Kanda S, Hashimoto J, Hamasaki Y, Hotta K, Ito N, Honda K, Tanabe K, Takano T, Hattori M. A multi-institutional study found a possible role of anti-nephrin antibodies in post-transplant focal segmental glomerulosclerosis recurrence. Kidney Int. 2024 Mar;105(3):608-617. doi: 10.1016/j.kint.2023.11.022. Epub 2023 Dec 16.

  PMID: 38110152 BACKGROUND

MeSH Terms

Conditions

Nephrotic Syndrome; Nephrosis, Lipoid; Glomerulosclerosis, Focal Segmental

Condition Hierarchy (Ancestors)

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

Study Officials

• Giuseppe Remuzzi, MD

  Istituto Di Ricerche Farmacologiche Mario Negri

  STUDY DIRECTOR

Central Study Contacts

Federica Casiraghi, PhD

CONTACT

+3903545351; federica.casiraghi@marionegri.it

Norberto Perico, MD

CONTACT

+3903545351; norberto.perico@marionegri.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2024
• First Posted: March 28, 2024
• Study Start: March 19, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: September 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)