- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05875454
Podocyts Integrity in Glomerular Diseases
Assessment of Podocyts Integrity in Glomerular Diseases.
- 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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Aya Salah, administrator
- Phone Number: 01095538980
- Email: ayaasalah23@gmail.com
Study Contact Backup
- Name: Ghada Hosney, lecturer
- Phone Number: 01062778691
- Email: Ghada_h@aun.edu.eg
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Patients undergoing renal biopsy and diagnosed as glomerular disease.
Exclusion Criteria:
- Patients diagnosed as tubule-interstitial diseases.
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
assessment of podocytes integrity in different glomerular disaeses.
Time Frame: 14 months
|
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
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Guo JK, Menke AL, Gubler MC, Clarke AR, Harrison D, Hammes A, Hastie ND, Schedl A. WT1 is a key regulator of podocyte function: reduced expression levels cause crescentic glomerulonephritis and mesangial sclerosis. Hum Mol Genet. 2002 Mar 15;11(6):651-9. doi: 10.1093/hmg/11.6.651.
- Barutta F, Bellini S, Gruden G. Mechanisms of podocyte injury and implications for diabetic nephropathy. Clin Sci (Lond). 2022 Apr 14;136(7):493-520. doi: 10.1042/CS20210625.
- Sever S. Role of actin cytoskeleton in podocytes. Pediatr Nephrol. 2021 Sep;36(9):2607-2614. doi: 10.1007/s00467-020-04812-z. Epub 2020 Nov 13.
- Kravets I, Mallipattu SK. The Role of Podocytes and Podocyte-Associated Biomarkers in Diagnosis and Treatment of Diabetic Kidney Disease. J Endocr Soc. 2020 Mar 5;4(4):bvaa029. doi: 10.1210/jendso/bvaa029. eCollection 2020 Apr 1.
- Nagata M. Podocyte injury and its consequences. Kidney Int. 2016 Jun;89(6):1221-30. doi: 10.1016/j.kint.2016.01.012. Epub 2016 Mar 19.
- Dong L, Pietsch S, Englert C. Towards an understanding of kidney diseases associated with WT1 mutations. Kidney Int. 2015 Oct;88(4):684-90. doi: 10.1038/ki.2015.198. Epub 2015 Jul 8.
- Lal MA, Patrakka J. Understanding Podocyte Biology to Develop Novel Kidney Therapeutics. Front Endocrinol (Lausanne). 2018 Jul 23;9:409. doi: 10.3389/fendo.2018.00409. eCollection 2018.
- Mathieson PW. The podocyte as a target for therapies--new and old. Nat Rev Nephrol. 2011 Nov 1;8(1):52-6. doi: 10.1038/nrneph.2011.171.
- Muller-Deile J, Schiffer M. Podocyte directed therapy of nephrotic syndrome-can we bring the inside out? Pediatr Nephrol. 2016 Mar;31(3):393-405. doi: 10.1007/s00467-015-3116-4. Epub 2015 May 5.
- Testagrossa L, Azevedo Neto R, Resende A, Woronik V, Malheiros D. Immunohistochemical expression of podocyte markers in the variants of focal segmental glomerulosclerosis. Nephrol Dial Transplant. 2013 Jan;28(1):91-8. doi: 10.1093/ndt/gfs325. Epub 2012 Aug 1.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- podocytes in glomeruli
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Glomerular Disease
-
National Institute of Diabetes and Digestive and...Completed
-
Medical University of LodzRecruitingGlomerular DiseasePoland
-
University Health Network, TorontoCompletedGlomerular Filtration Rate | Renal Blood FlowCanada
-
Paris Translational Research Center for Organ TransplantationCompletedKidney Transplantation | Glomerular Filtration RateUnited States, Croatia, France, Italy
-
Mårten SegelmarkHansa Biopharma ABCompletedAnti-Glomerular Basement Membrane Antibody DiseaseAustria, Czechia, Denmark, France, Sweden
-
Children's Hospital of PhiladelphiaNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); American... and other collaboratorsCompleted
-
University of MichiganNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)TerminatedWeight Gain | Glomerular Disease | Kidney Transplant; Complications | Kidney TransplantUnited States
-
The University of Texas Health Science Center,...Not yet recruitingAnemia | Decreased Glomerular Filtration RateUnited States
-
Medical University of ViennaCompletedGlomerular Filtration Rate | Fatty Acids, Nonesterified | Renal Circulation | Renal Plasma FlowAustria
-
Rabin Medical CenterUnknown
Clinical Trials on Histopathological examination of tru-cut needle biopsy
-
Indiana UniversityCompletedNon-alcoholic Fatty Liver Disease | Nonalcoholic SteatohepatitisUnited States
-
Udo SechtemTerminated
-
University Hospital, MontpellierRecruitingMechanical Ventilation Complication | Diaphragm InjuryFrance
-
Universitaire Ziekenhuizen KU LeuvenUZ Leuven, Leuven, Belgium; Policlinico Universitario A. Gemelli, IRCSS, Rome... and other collaboratorsRecruitingCervical Cancer | Ovarian Neoplasms | Ovarian Cancer | Metastatic Cancer | Pelvic Cancer | Endometrial Cancer | Ovarian Carcinoma | Uterus Cancer | Sarcoma UterusBelgium, Czechia, Italy, Sweden
-
Region SkaneRecruitingProstate Cancer (Diagnosis)Sweden
-
Modarres HospitalCompleted
-
Assiut UniversityUnknown
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingMalignant NeoplasmUnited States
-
Uro-1 MedicalRecruiting