The Role of Renal Progenitors and Polyploid Tubular Cell Response in Glomerular and Tubular Diseases

March 15, 2024 updated by: Paola Romagnani, Meyer Children's Hospital IRCCS

Studying the Role of Renal Progenitors and Polyploid Tubular Cell Response in Glomerular and Tubular Diseases: Analysis on Renal Biopsies

Renal progenitors are a subset of parietal epithelial cells (PECs) localized at the urinary pole of Bowman's capsule. Experimental models of podocyte damage showed that PECs can potentially regenerate lost podocytes by migrating from Bowman's capsule to the glomerular tuft, acquiring the morphological and functional features of mature podocytes. Podocyte loss and damage, as well as the inability of PECs to replace lost podocytes, lead to glomerular scarring and chronic kidney disease (CKD) progression.

In addition, the investigators of the present study and others have recently demonstrated the existence of a specific subpopulation of tubular cells in the human kidney with a high potential for regeneration and resistance to death, thus acting as tubular progenitors. These cells are involved in tubular response to damage during acute kidney injury (AKI) trough endoreplication (polyploidization).

Kidney biopsy is the cornerstone of diagnosis in many kidney diseases leading to CKD and AKI, allowing unambiguous diagnosis in some cases and presumptive diagnosis of ongoing disease in others. Very recently, super resolution imaging techniques proved to maintain current diagnostic standards while allowing to study morphological features of pathophysiological mechanisms of glomerular and tubular diseases.

The rationale of this project is to study the role of renal progenitors (PECs and tubular progenitors) in the pathogenesis of CKD and AKI trough super resolution imaging applied to human renal biopsies, to the aim of identifying relevant connections with clinical data and markers of damage and/or disease progression.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Not Applicable

Contacts and Locations

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

Study Contact

Study Locations

  • Italy
      • Firenze, Italy
        • Recruiting
        • Meyer Children's Hospital IRCCS
        • Contact:
          • Paola Romagnani

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

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with glomerular diseases undergoing renal biopsy (e.g., rapidly progressive glomerulonephritis, minimal change disease, focal segmental glomerulosclerosis, diabetic nephropathy, lupus nephritis, membranous nephropathy, IgA nephropathy, etc)
  • Patients with AKI, regardless of the nature of the damage (septal, ischemic, toxic, or unknown).
  • Signed informed consent form

Exclusion Criteria:

  • Sample insufficient and/or unavailable

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

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patients with kidney diseases undergoing renal biopsy
Patients with kidney diseases undergoing renal biopsy for diagnostic purposes
Other: Study of renal progenitors
Evaluation of the role of renal progenitors in pathogenesis and mechanisms of disease progression in kidney biopsies performed for diagnostic purposes

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of the role of renal progenitors in the progression of glomerular diseases
Time Frame: Clinical data will be collected at enrollment (kidney biopsy) and at 3, 6 and 12 months from enrollment, then annually until the end of the study (up to 9 years)

The presence renal progenitors will be assessed by immunofluorescence and confocal microscopy on histological sections from renal biopsy performed for diagnostic purposes.

The following features will be assessed and correlated with clinical parameters of renal function:

  • number of renal progenitors (CD133+CD24+CD106+ cells/section);
  • number of podocyte progenitors (CD133+WT1+, CD24+synaptopodin, CD24+podocin+ cells/section);
  • number of activated progenitors in the Bowman's capsule (CD133+SFN+/section)
  • quantitative and semiqualitative analysis of the slit diaphragm
  • presence and characterization of immune complexes
Clinical data will be collected at enrollment (kidney biopsy) and at 3, 6 and 12 months from enrollment, then annually until the end of the study (up to 9 years)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of the role of tubular endoreplication in mechanisms of acute kidney injury (AKI)
Time Frame: Clinical data will be collected at enrollment (kidney biopsy) and at 3, 6 and 12 months from enrollment, then annually until the end of the study (up to 9 years)

The presence of tubular progenitors will be assessed by immunofluorescence and confocal microscopy evaluation on histological sections from renal biopsy performed for diagnostic purposes. The presence of polyploid tubular cells will be assessed using specific markers.

In particular, the following features will be assessed:

  • number of tubular progenitors (CD133+CD24+CD106- cells) over the total of tubular cells (phaIIoidin+, AQP1+, THP+, AQP2+ cells);
  • number of Ki-67+ or PCNA+ over the total of tubular cells (%);
  • number of polyploid tubular cells (CDK4+ or CDT1+ and p-H3+) over the total of tubular cells;
Clinical data will be collected at enrollment (kidney biopsy) and at 3, 6 and 12 months from enrollment, then annually until the end of the study (up to 9 years)
Evaluation of the role of tubular endoreplication in mechanisms of acute kidney injury (AKI) trough DNA and RNA analysis
Time Frame: Clinical data will be collected at enrollment (kidney biopsy) and at 3, 6 and 12 months from enrollment, then annually until the end of the study (up to 9 years)

The presence of tubular progenitors will be assessed by immunofluorescence and confocal microscopy evaluation on histological sections from renal biopsy performed for diagnostic purposes. The presence of polyploid tubular cells will be assessed using specific markers, in particular:

  • DNA content (fluorescence intensity of Picogreen/YAP1 staining);
  • RNA expression of polyploidy markers (TMSB10, SEMA5a, VCAM1, BIRC5, AKT, E2F7, E2F8, CDK1, CCNB1)
Clinical data will be collected at enrollment (kidney biopsy) and at 3, 6 and 12 months from enrollment, then annually until the end of the study (up to 9 years)

Collaborators and Investigators

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

Sponsor

Meyer Children's Hospital IRCCS

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)

March 22, 2023

Primary Completion (Estimated)

March 22, 2047

Study Completion (Estimated)

November 30, 2047

Study Registration Dates

First Submitted

February 29, 2024

First Submitted That Met QC Criteria

March 15, 2024

First Posted (Actual)

March 22, 2024

Study Record Updates

Last Update Posted (Actual)

March 22, 2024

Last Update Submitted That Met QC Criteria

March 15, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BIO-KIDNEY

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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