Immunophenotyping Profiling in Patients With Primary Nephrotic Syndrome

July 8, 2026 updated by: Christos Georgopoulos, University Hospital, Ioannina

Immunophenotyping Profiling in Patients With Nephrotic Syndrome: Emphasis on the Diagnostic and Prognostic Value of Immune Cells in the Different Phenotypes of Nephrotic Syndrome.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Actual)

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Greece
    • Epirus
      • Ioannina, Epirus, Greece, 45500
        • University Hospital of Ioannina

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adult patients with primary MN, MCD and primary FSGS

Description

Inclusion Criteria:

  1. Patients with nephrotic syndrome and a biopsy-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:

  1. Patients with nephrotic syndrome in whom membranous nephropathy, primary FSGS, or MCD has not been confirmed by renal biopsy (and who do not meet Inclusion Criterion 2).
  2. Patients with secondary causes of nephrotic syndrome (malignancy, autoimmune disease, drug-induced, etc.).
  3. Patients with active malignancy.
  4. Patients with severe heart failure (NYHA 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Primary Membranous Nephropathy
Patients with primary MN
Drug: Rituximab (MABTHERA® or RITUXAN®).
Patients with primary MN treated with Rituximab
FSGS
Patients with primary focal segmental glomerulosclerosis
Drug: Corticosteroids (CS)
Patients with MCD treated with Corticosteroids
Drug: Corticosteroids (CS)
Patients with primary FSGS treated with Corticosteroids
MCD
Patients with minimal change disease
Drug: Corticosteroids (CS)
Patients with MCD treated with Corticosteroids
Drug: Corticosteroids (CS)
Patients with primary FSGS treated with Corticosteroids

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Partial Remission
Time Frame: 12 months
Urine protein to creatinine ratio< 3.5 g/g and >50 % reduction from baseline
12 months
Complete Remission
Time Frame: 12 months
Urine protein to creatinine ratio <0.3 g/g
12 months
Relapse
Time Frame: 24 months
Urine protein to creatinine ratio>3.5 g/g
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite renal outcome
Time Frame: 24 months
>50% decline in eGFR (CKD-EPI) from baseline, and/or initiation of kidney replacement therapy
24 months
Cardiovascular events
Time Frame: 24 months
Incident cardiovascular events during follow-up
24 months
Thromboembolic events
Time Frame: 24 months
Incident venous or arterial thromboembolic events
24 months
Infections
Time Frame: 24 months
Incident infections requiring medical evaluation or treatment
24 months
Hospitalization
Time Frame: 24 months
All-cause hospitalization
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Ioannina

Investigators

  • Study Director: Evangelia Dounousi, Medical Degree, University of Ioannina

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2023

Primary Completion (Actual)

November 1, 2025

Study Completion (Actual)

February 1, 2026

Study Registration Dates

First Submitted

July 2, 2026

First Submitted That Met QC Criteria

July 8, 2026

First Posted (Actual)

July 14, 2026

Study Record Updates

Last Update Posted (Actual)

July 14, 2026

Last Update Submitted That Met QC Criteria

July 8, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 695

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Summary Statistics including tables, figures and advanced statistics results (univariate/multivariate logistic regression results and kaplan meier survival analysis)

IPD Sharing Access Criteria

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

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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