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NCT Number: NCT06325059

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

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.

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Key information

Conditions

Nephropathy Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Male Urogenital Diseases Urogenital Diseases Urologic Diseases

Age range

1 month–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Meyer Children's Hospital IRCCS

Florence, Italy

Location status: Recruiting

Location contact

Paola Romagnani

CONTACT

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Study of renal progenitors

Other

Evaluation of the role of renal progenitors in pathogenesis and mechanisms of disease progression in kidney biopsies performed for diagnostic purposes

Primary outcomes

  1. 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

Secondary outcomes

  1. 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;

  2. 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)

Study contacts

Contact information is provided by the study sponsor or research team.

Paola Romagnani, MD

CONTACT

[email protected]

055 5662562

Sponsors and collaborators

Lead sponsor

Meyer Children's Hospital IRCCS

Other

Registry information

Official study title

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

Important dates

Study start
2023
Primary completion
2047
Study completion
2047
First posted
Mar 22, 2024
Registry last updated
Mar 22, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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