Studying the Role of Renal Progenitors and Polyploid Tubular Cell Response in Glomerular and Tubular Diseases: Analysis on Renal Biopsies
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Evaluation of the role of renal progenitors in the progression of glomerular diseases
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 1 Month 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Sample insufficient and/or unavailable
研究组 & 干预措施
Patients with kidney diseases undergoing renal biopsy
Patients with kidney diseases undergoing renal biopsy for diagnostic purposes
干预措施: Study of renal progenitors (Other)
结局指标
主要结局
Evaluation of the role of renal progenitors in the progression of glomerular diseases
时间窗: 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
次要结局
- 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))
研究者
Paola Romagnani
Professor, MD, PhD
Meyer Children's Hospital IRCCS