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

Official title

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

Overview

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.

Interventions

• 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

Primary outcome measures

• 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)]

Secondary outcome measures (2)

• 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)]
• 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)]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

Italy · 1 center

• Meyer Children's Hospital IRCCS — Florence

Identifiers

NCT: NCT06325059 · BIO-KIDNEY

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗