Podocyts Integrity in Glomerular Diseases

Study Overview
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Brief Summary
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To assess the density and ultrastructural morphology of podocytes in different glomerular diseases. Correlate the podocyte density and ultrastuctural morphology with laboratory data, the histopathological diagnosis and the active and chronic histopathological lesions in the biopsy.

Detailed Description
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Glomerular diseases are common causes of end-stage renal failure. Increasing evidence suggests that these glomerulopathies are frequently caused by primary lesions in the renal podocytes. Podocytes are highly specialized glomerular epithelial cells that form the glomerular filtration barrier together with the fenestrated endothelium and the glomerular basement membrane. The podocyte cell body bulges into the urinary space and gives long processes that branch into foot processes, enwrapping the glomerular capillaries. Adjacent podocytes interdigitate with each other at their foot processes which are bridged with a specialized intercellular junction called a slit diaphragm, which is evenly spaced areas covered by slit diaphragm proteins that facilitate podocyte-to-podocyte contact. Podocytes live under various stresses and pathological stimuli. They adapt to maintain homeostasis, but excessive stress leads to maladaptation and injury. Podocyte injury causes proteinuria, ranging from albuminuria to massive nephrotic syndrome. The integrity of podocytes and their interaction with the glomerular basement membrane is crucial for maintenance of the intact glomerular filtration barrier. Alteration of the intercellular junctions and cytoskeletal structure of podocytes or their detachment from the membrane results in the development of albuminuria. Podocyte density is one of the best predictors of the progression in glomerular diseases. The number of podocytes seems to be very critical for kidney health as the loss of podocytes results in glomerular damage. Thus, the extent of podocyte damage and loss seems to define the progression rate in many kidney disease. As podocytes have limited ability to repair and/or regenerate, the extent of podocyte injury is a major prognostic determinant in glomerular diseases. Therapies aimed at preventing or limiting podocyte injury and/or at promoting podocyte repair or regeneration therefore have major potential benefits. Podocytes display a remarkable ability to recover from complete effacement and to re-form interdigitating foot processes and intact slit diaphragms after pharmacological intervention. Podocytes are the main sites of expression of the wilm's tumor suppressor gene, WT1, in the adult. WT1 is a complex gene, which plays an essential role in renal development by controlling the process of mesenchymal to epithelial transition that form the nephron. Adult podocyte maintains both epithelial and mesenchymal features and continue to express high levels of WT1. Several lines of evidence suggest that WT1 may indeed play an important role in the maintenance of normal podocyte function. Mutations in Wilms' tumor 1 cause a wide spectrum of renal manifestations, eventually leading to end-stage kidney failure. WT1 mutations have been found to cause up to 12 % of steroid resistant nephrotic syndrome in children and young adults, particularly in phenotypic females.

Official Title
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Assessment of Podocyts Integrity in Glomerular Diseases.

Conditions
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Glomerular Disease

Intervention / Treatment
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* Diagnostic Test: Histopathological examination of tru-cut needle biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing renal biopsy and diagnosed as glomerular disease. Exclusion Criteria: Patients diagnosed as tubule-interstitial diseases.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Histopathological examination of tru-cut needle biopsy|Renal biopsies fixed in formalin from patients with suspected medical renal disease will be processed and examined for histopathological diagnosis.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| assessment of podocytes integrity in different glomerular disaeses. | Assessment of podocytes density which will be detected by immunohistochemical expression of WT-1 in different glomerular diseases. Correletion between the podocytes density with laboratory data of the cases and the histopathological diagnosis. | 14 months |