Immunophenotyping Profiling in Patients With Primary Nephrotic Syndrome

NCT07702981 | Completed

• 1 other identifier: 695
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Immunophenotyping profiling of patients with primary MN, primary FSGS and MCD. Evaluation of these immune cell subsets as possible biomarkers to track response to treatment or disease relapse.

Conditions

Membranous Nephropathy; Minimal Change Disease (MCD); Focal Segmental Glomerulosclerosis (FSGS)

Keywords

Nephrotic syndrome; primary MN; MCD; Immunophenotyping; Flow cytometry; Rituximab; Corticosteroids; primary FSGS

Outcome Measures

Primary Outcomes (3)

• Partial Remission

  Urine protein to creatinine ratio\< 3.5 g/g and \>50 % reduction from baseline

  12 months

• Complete Remission

  Urine protein to creatinine ratio \<0.3 g/g

  12 months

• Relapse

  Urine protein to creatinine ratio\>3.5 g/g

  24 months

Secondary Outcomes (5)

• Composite renal outcome

  24 months

• Cardiovascular events

  24 months

• Thromboembolic events

  24 months

• Infections

  24 months

• Hospitalization

  24 months

Study Arms (3)

Primary Membranous Nephropathy

Patients with primary MN

Drug: Rituximab (MABTHERA® or RITUXAN®).

FSGS

Patients with primary focal segmental glomerulosclerosis

Drug: Corticosteroids (CS)

MCD

Patients with minimal change disease

Drug: Corticosteroids (CS)

Interventions

Rituximab (MABTHERA® or RITUXAN®). DRUG

Patients with primary MN treated with Rituximab

Primary Membranous Nephropathy

Corticosteroids (CS) DRUG

Patients with MCD treated with Corticosteroids

MCD

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

Adult patients with primary MN, MCD and primary FSGS

You may qualify if:

• Patients with nephrotic syndrome and a biopsy-confirmed diagnosis of membranous nephropathy, primary focal segmental glomerulosclerosis, or minimal change disease.
• Patients with membranous nephropathy and positive serum anti-PLA2R antibodies, in the absence of histological confirmation by renal biopsy.
• Patients with a previously confirmed diagnosis of primary nephrotic syndrome who present with disease relapse requiring re-induction therapy.

You may not qualify if:

• Patients with secondary causes of nephrotic syndrome (malignancy, autoimmune disease, drug-induced, etc.).
• Patients with active malignancy.
• Patients with severe heart failure (NYHA class IV) or hepatic failure.
• Patients with active infection or inflammation.
• Patients receiving, or who received within the preceding 6 months, immunomodulatory agents for an unrelated condition.

Sponsors & Collaborators

• University Hospital, Ioannina: lead

Study Sites (1)

University Hospital of Ioannina

Ioannina, Epirus, 45500, Greece

Location

Related Publications (14)

• Ishimoto T, Shimada M, Araya CE, Huskey J, Garin EH, Johnson RJ. Minimal change disease: a CD80 podocytopathy? Semin Nephrol. 2011 Jul;31(4):320-5. doi: 10.1016/j.semnephrol.2011.06.002.

  PMID: 21839364 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

• Hengel FE, Dehde S, Lasse M, Zahner G, Seifert L, Schnarre A, Kretz O, Demir F, Pinnschmidt HO, Grahammer F, Lucas R, Mehner LM, Zimmermann T, Billing AM, Oh J, Mitrotti A, Pontrelli P, Debiec H, Dossier C, Colucci M, Emma F, Smoyer WE, Weins A, Schaefer F, Alachkar N, Diemert A, Hogan J, Hoxha E, Wiech T, Rinschen MM, Ronco P, Vivarelli M, Gesualdo L, Tomas NM, Huber TB; International Society of Glomerular Disease. Autoantibodies Targeting Nephrin in Podocytopathies. N Engl J Med. 2024 Aug 1;391(5):422-433. doi: 10.1056/NEJMoa2314471. Epub 2024 May 25.

  PMID: 38804512 BACKGROUND

• Yap HK, Cheung W, Murugasu B, Sim SK, Seah CC, Jordan SC. Th1 and Th2 cytokine mRNA profiles in childhood nephrotic syndrome: evidence for increased IL-13 mRNA expression in relapse. J Am Soc Nephrol. 1999 Mar;10(3):529-37. doi: 10.1681/ASN.V103529.

  PMID: 10073603 BACKGROUND

• Bertelli R, Bonanni A, Di Donato A, Cioni M, Ravani P, Ghiggeri GM. Regulatory T cells and minimal change nephropathy: in the midst of a complex network. Clin Exp Immunol. 2016 Feb;183(2):166-74. doi: 10.1111/cei.12675. Epub 2015 Oct 12.

  PMID: 26147676 BACKGROUND

• Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, Klein JB, Salant DJ. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009 Jul 2;361(1):11-21. doi: 10.1056/NEJMoa0810457.

  PMID: 19571279 BACKGROUND

• Logt AV, Justino J, Vink CH, van den Brand J, Debiec H, Lambeau G, Wetzels JF. Anti-PLA2R1 Antibodies as Prognostic Biomarker in Membranous Nephropathy. Kidney Int Rep. 2021 Apr 22;6(6):1677-1686. doi: 10.1016/j.ekir.2021.04.002. eCollection 2021 Jun.

  PMID: 34169209 BACKGROUND

• Rosenzwajg M, Languille E, Debiec H, Hygino J, Dahan K, Simon T, Klatzmann D, Ronco P. B- and T-cell subpopulations in patients with severe idiopathic membranous nephropathy may predict an early response to rituximab. Kidney Int. 2017 Jul;92(1):227-237. doi: 10.1016/j.kint.2017.01.012. Epub 2017 Mar 15.

  PMID: 28318628 BACKGROUND

• Hou J, Zhang M, Ding Y, Wang X, Li T, Gao P, Jiang Y. Circulating CD14+CD163+CD206+ M2 Monocytes Are Increased in Patients with Early Stage of Idiopathic Membranous Nephropathy. Mediators Inflamm. 2018 Jun 21;2018:5270657. doi: 10.1155/2018/5270657. eCollection 2018.

  PMID: 30034290 BACKGROUND

• Gaggar P, Madipally R, Raju SB. Rituximab, Use and B Cell Depletion in Patients with Membranous Nephropathy- A Retrospective, Observational Study. Indian J Nephrol. 2023 Sep-Oct;33(5):356-361. doi: 10.4103/ijn.ijn_62_22. Epub 2023 Apr 19.

  PMID: 37881741 BACKGROUND

• Duan S, Ye Y, Zhou Q, Hua H, Zeng M, Zhang C, Yuan Y, Xing C, Mao H, Zhang B. Systemic inflammation and B cell indices predict rituximab responses in membranous nephropathy. Clin Kidney J. 2025 Dec 18;19(2):sfaf396. doi: 10.1093/ckj/sfaf396. eCollection 2026 Feb.

  PMID: 41658280 BACKGROUND

• Colucci M, Carsetti R, Cascioli S, Casiraghi F, Perna A, Rava L, Ruggiero B, Emma F, Vivarelli M. B Cell Reconstitution after Rituximab Treatment in Idiopathic Nephrotic Syndrome. J Am Soc Nephrol. 2016 Jun;27(6):1811-22. doi: 10.1681/ASN.2015050523. Epub 2015 Nov 13.

  PMID: 26567244 BACKGROUND

• Cheddadi Y, El Mai M, Brglez V, Nahon Carzo S, Cremoni M, Teisseyre M, Seitz-Polski B. Early-Stage B-cells Predict Relapse After Rituximab Treatment in Patients With Membranous Nephropathy. Kidney Int Rep. 2026 Feb 19;11(5):106365. doi: 10.1016/j.ekir.2026.106365. eCollection 2026 May. No abstract available.

  PMID: 41907818 BACKGROUND

• Cantarelli C, Jarque M, Angeletti A, Manrique J, Hartzell S, O'Donnell T, Merritt E, Laserson U, Perin L, Donadei C, Anderson L, Fischman C, Chan E, Draibe J, Fulladosa X, Torras J, Riella LV, La Manna G, Fiaccadori E, Maggiore U, Bestard O, Cravedi P. A Comprehensive Phenotypic and Functional Immune Analysis Unravels Circulating Anti-Phospholipase A2 Receptor Antibody Secreting Cells in Membranous Nephropathy Patients. Kidney Int Rep. 2020 Aug 1;5(10):1764-1776. doi: 10.1016/j.ekir.2020.07.028. eCollection 2020 Oct.

  PMID: 33102969 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum and plasma samples will be biobanked at -80C at baseline and at each follow-up time point. In addition to the assays specified, banked samples may be used for exploratory analysis of additional inflammatory, coagulation, and lipid-pathway biomarkers not included in the routine panel, at a later stage of the study.

MeSH Terms

Conditions

Glomerulonephritis, Membranous; Nephrosis, Lipoid; Glomerulosclerosis, Focal Segmental; Nephrotic Syndrome; Macular dystrophy, corneal type 1

Interventions

Rituximab; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Evangelia Dounousi, Medical Degree

  University of Ioannina

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 24 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Christos Georgopoulos, MD, MSc, PhD(c), Resident Physician of Nephrology

Study Record Dates

• First Submitted: July 2, 2026
• First Posted: July 14, 2026
• Study Start: June 1, 2023
• Primary Completion: November 1, 2025
• Study Completion: February 1, 2026
• Last Updated: July 14, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Access Criteria: Data regarding methods and results presented in this study are available upon reasonable request from the primary investigator.

Locations

GR (1)