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

Condition(s) studied

Investigational drug(s) / intervention(s)

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

Study 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.

Eligibility

Primary outcome measure(s)

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

Trial sites (1)

More Meyer Children's Hospital IRCCS trials in Italy