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

NCT06325059 | Recruiting

• 1 other identifier: BIO-KIDNEY
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Nephropathy

Outcome Measures

Primary Outcomes (1)

• Evaluation of the role of renal progenitors in the progression of glomerular diseases

  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 Outcomes (2)

• Evaluation of the role of tubular endoreplication in mechanisms of acute kidney injury (AKI)

  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

  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)

Study Arms (1)

Patients with kidney diseases undergoing renal biopsy

EXPERIMENTAL

Patients with kidney diseases undergoing renal biopsy for diagnostic purposes

Other: Study of renal progenitors

Interventions

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

Patients with kidney diseases undergoing renal biopsy

Eligibility Criteria

• Age: 1 Month - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• Sample insufficient and/or unavailable

Sponsors & Collaborators

• Meyer Children's Hospital IRCCS: lead

Study Sites (1)

Meyer Children's Hospital IRCCS

Florence, Italy

RECRUITING

MeSH Terms

Conditions

Kidney Diseases

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Central Study Contacts

Paola Romagnani, MD

CONTACT

055 5662562; paola.romagnani@meyer.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD, PhD

Model Details: Patients affected by nephropathy

Study Record Dates

• First Submitted: February 29, 2024
• First Posted: March 22, 2024
• Study Start: March 22, 2023
• Primary Completion (Estimated): March 22, 2047
• Study Completion (Estimated): November 30, 2047
• Last Updated: March 22, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)