ClinicalTrials.gg
CompletedNCT07702981Updated Jul 14, 2026

Immunophenotyping Profiling in Patients With Primary Nephrotic Syndrome

An observational study in Membranous Nephropathy, Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS), sponsored by University Hospital, Ioannina. Completed at 1 site in Greece. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-14.

Sponsored by University Hospital, Ioannina · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
40
Ages
18 Years and older
Sex
All
01

Study 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.

Read the detailed description

Primary nephrotic syndrome caused by membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), or minimal change disease (MCD) is, in each case, associated with dysregulation of specific innate and adaptive immune cell populations. However, the relationship between circulating immune cell subsets and key clinical outcomes, specifically treatment response and disease relapse, remains incompletely defined, and the classical clinical and laboratory markers currently used to monitor these diseases are non-specific and have limited predictive value.

The principal parameter used clinically to monitor treatment response remains 24-hour urinary protein excretion. Complete remission is defined as a reduction in proteinuria to below 0.3 g/24h, and partial remission as a reduction of ≥50% from baseline together with total proteinuria below 3.5 g/24h. Non-response is defined as persistent proteinuria above 3.5 g/24h despite guideline-directed therapy, and relapse as recurrence of proteinuria above 3.5 g/24h in a patient who had previously achieved complete remission.

In MN specifically, serum anti-PLA2R antibody titers provide an additional marker of immunological disease activity: a decline in antibody levels can precede and predict clinical response, while re-emergence or a rise in titer in a patient previously in remission can predict relapse.

Despite the established contribution of specific immune cell populations to primary nephrotic syndrome, the literature remains comparatively sparse regarding abnormalities in regulatory T-cell subsets, monocyte subsets, B-cell subsets (including CD5+ B cells), T-helper subsets, and NK cells, and their potential role in disease pathogenesis across MN, MCD, and FSGS. Furthermore, classical clinical and immunological biomarkers of disease activity and treatment response are non-specific, correlate poorly with the degree of underlying renal injury, and in most cases cannot predict renal outcome. Anti-PLA2R1 antibody titers capture humoral activity and glomerular injury, but only partially explain this heterogeneity, are informative in only 70-80% of patients and frequently lag behind cellular events.

Whether changes in specific circulating immune cell subsets are associated with clinical outcomes in primary nephrotic syndrome, and whether they add predictive value beyond classical markers, remains an open question that this study is designed to address.

This prospective, single-center cohort study will enroll adult patients with either de novo or relapsing primary MN, primary FSGS and MCD, diagnosed by renal biopsy , who underwent rituximab (RTX) or corticosteroids treatment at the University Hospital of Ioannina between JUN 2023 and NOV 2025. Baseline was defined as the time of treatment initiation.

Baseline Assessment - Month 0

  1. Demographic and clinical data: sex, age, smoking status, alcohol use, obesity, family history, and comorbidities, with particular attention to hypertension, diabetes mellitus, dyslipidemia, coronary artery disease, and coexisting autoimmune disease. A full clinical examination will be performed (systems review, blood pressure, pulse, weight, height, body mass index), and current medications will be recorded.
  2. Routine laboratory assessment (at baseline and at regular intervals thereafter, per current standards of care for primary nephrotic syndrome): complete blood count, INR, comprehensive metabolic panel (glucose, urea, creatinine, potassium, sodium, calcium, phosphate, AST, ALT, CPK, GGT, alkaline phosphatase, total serum protein, HDL and LDL cholesterol, triglycerides, HbA1c, iron, TIBC, ferritin), inflammatory markers (CRP, ESR), urinalysis, and UPCR/UACR (creatinine, urea, protein, albumin, sodium). Estimated glomerular filtration rate will be calculated using the CKD-EPI creatinine equation.
  3. Disease-specific serology: in patients with confirmed membranous nephropathy, serum anti-PLA2R antibody titers will be measured per the KDIGO 2021 Clinical Practice Guideline for Glomerular Diseases.
  4. Annual assessments: viral serology and tumor markers (HBsAg, HBsAb, HBcAb, anti-HCV, AFP, CA 19-9, CA 15-3, CEA, CA-125, PSA); lipid panel (apo-A, apo-B, Lp(a)) and fasting insulin.

After baseline serum creatinine, eGFR (CKD-EPI), albumin, urine protein-to-creatinine ratio (UPCR), urine albumin-to-creatinine ratio (UACR), lipid parameters and inflammatory markers (ESR, CRP) were measured every month after treatment.

Anti-PLA2R antibody levels were measured at baseline and months 3,6 and 12 respectively.

Peripheral-blood immune-cell subsets were analysed by flow cytometry at baseline and at months 3, 6 and 12.

The following immune cell subsets were measured through flow cytometry:

  1. B-cell compartment: total CD3-CD19+; CD19+CD27+IgD+ (non-switched memory); CD19+CD27+IgD- (class-switched memory); CD19+CD27-IgD+ (naïve mature); CD19+CD5+ (regulatory B cells, Bregs).
  2. T-cell compartment: CD3+; CD3+CD4+; CD3+CD8+; CD4/CD8 ratio; CD4+CD25+FoxP3+ (regulatory T cells, Tregs); CD4+CD45RA+ (naïve); CD4+CD45RO+ (memory); CD45RA+RO+ (transitional).
  3. Monocyte compartment: total monocytes; CD14++CD16- (classical); CD14++CD16+ (intermediate); CD14+CD16++ (non-classical); CD14+HLA-DR+ (activated).
  4. CD16+CD56+ (NK cells).

The study aims to determine whether baseline levels and treatment-related changes in these immune cell subsets are associated with treatment response and disease relapse, and to correlate them with standard clinical and laboratory markers of renal function and disease activity.

02

Conditions studied

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

Keywords

  • Nephrotic syndrome
  • primary MN
  • MCD
  • Immunophenotyping
  • Flow cytometry
  • Rituximab
  • Corticosteroids
  • primary FSGS
03

In context

Glomerulonephritis, Membranous

144 studies on the registry are indexed under Glomerulonephritis, Membranous; 58 are open to participants now.

This study's enrollment of 40 is below the median of 120 across 35 observational studies indexed under Glomerulonephritis, Membranous.

Browse Glomerulonephritis, Membranous studies →

Lead sponsor

University Hospital, Ioannina is the lead sponsor of 13 studies on the registry; 4 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

Adult patients with primary MN, MCD and primary FSGS

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

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

Exclusion criteria

Exclusion Criteria:

  1. Patients with nephrotic syndrome in whom membranous nephropathy, primary FSGS, or MCD has not been confirmed by renal (and who do not meet Inclusion Criterion 2).
  2. Patients with secondary causes of nephrotic syndrome (, disease, drug-induced, etc.).
  3. Patients with active malignancy.
  4. Patients with severe heart failure ( class IV) or hepatic failure.
  5. Patients with active infection or inflammation.
  6. Patients receiving, or who received within the preceding 6 months, immunomodulatory agents for an unrelated condition.
Terms in these criteria, in plain language(4)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Autoimmune disease

A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.

Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.

NYHA class (heart failure)

The New York Heart Association’s four classes of how much heart failure limits physical activity.

I
No limits: ordinary activity causes no undue tiredness or breathlessness.
II
Slight limits: comfortable at rest, ordinary activity causes symptoms.
III
Marked limits: comfortable at rest, less than ordinary activity causes symptoms.
IV
Symptoms even at rest; any activity makes them worse.

Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.

05

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
40 participants (actual)
Target follow-up
24 Months
Patient registry
Yes
Biospecimen retention
Samples without dna

Groups and cohorts

  • 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

  • DrugRituximab (MABTHERA® or RITUXAN®).

    Patients with primary MN treated with Rituximab

  • DrugCorticosteroids (CS)

    Patients with MCD treated with Corticosteroids

  • DrugCorticosteroids (CS)

    Patients with primary FSGS treated with Corticosteroids

06

What researchers measure

Primary outcomes

  1. Partial Remission

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

    Time frame: 12 months

  2. Complete Remission

    Urine protein to creatinine ratio \<0.3 g/g

    Time frame: 12 months

  3. Relapse

    Urine protein to creatinine ratio\>3.5 g/g

    Time frame: 24 months

Secondary outcomes

  1. Composite renal outcome

    \>50% decline in eGFR (CKD-EPI) from baseline, and/or initiation of kidney replacement therapy

    Time frame: 24 months

  2. Cardiovascular events

    Incident cardiovascular events during follow-up

    Time frame: 24 months

  3. Thromboembolic events

    Incident venous or arterial thromboembolic events

    Time frame: 24 months

  4. Infections

    Incident infections requiring medical evaluation or treatment

    Time frame: 24 months

  5. Hospitalization

    All-cause hospitalization

    Time frame: 24 months

07

Study locations

1 site
  • University Hospital of Ioannina
    Ioannina, Epirus 45500, Greece
08

References and documents

Publications

  • 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. PubMed 21839364 ↗
  • 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. PubMed 34732507 ↗
  • 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. PubMed 38804512 ↗
  • 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. PubMed 10073603 ↗
  • 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. PubMed 26147676 ↗
  • 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. PubMed 19571279 ↗
  • 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. PubMed 34169209 ↗
  • 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. PubMed 28318628 ↗
  • 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. PubMed 30034290 ↗
  • 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. PubMed 37881741 ↗
  • 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. PubMed 41658280 ↗
  • 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. PubMed 26567244 ↗
  • 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. PubMed 41907818 ↗
  • 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. PubMed 33102969 ↗

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: Yes — Summary Statistics including tables, figures and advanced statistics results (univariate/multivariate logistic regression results and kaplan meier survival analysis)

Supporting information: Study protocol

Access criteria: Data regarding methods and results presented in this study are available upon reasonable request from the primary investigator.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Jun 2023 to primary completion in Nov 2025, 29 months.

How these figures are worked out, and which studies are left out of them.

Registered
Jul 2, 2026
First posted
Jul 14, 2026
StartActual
Jun 1, 2023
Primary completionActual
Nov 1, 2025
CompletionActual
Feb 1, 2026
Last update
Jul 14, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jul 14, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT07702981
Lead sponsor
University Hospital, Ioannina
Responsible party
Christos Georgopoulos (Christos Georgopoulos, MD, MSc, PhD(c), Resident Physician of Nephrology, University Hospital, Ioannina) — Principal investigator
First posted
Jul 14, 2026
Start date
Jun 1, 2023
Primary completion
Nov 1, 2025
Completion
Feb 1, 2026
Last update
Jul 14, 2026

Study contacts

Evangelia Dounousi, Medical Degree
study director · University of Ioannina

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.

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