Podocyts Integrity in Glomerular Diseases

NCT ID: NCT05875454

Last Updated: 2023-06-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

50 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-07-31

Study Completion Date

2025-12-31

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.

Conditions

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Glomerular Disease

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Interventions

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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.

Intervention Type DIAGNOSTIC_TEST

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.
Minimum Eligible Age

10 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assiut University

OTHER

Sponsor Role lead

Responsible Party

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Aya Salah Rashed

principle investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Central Contacts

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Aya Salah, administrator

Role: CONTACT

01095538980

Ghada Hosney, lecturer

Role: CONTACT

01062778691

References

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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.

Reference Type BACKGROUND
PMID: 11912180 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35415751 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33188449 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32232184 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27165817 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26154924 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30083135 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22045242 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25939817 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22859792 (View on PubMed)

Other Identifiers

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podocytes in glomeruli

Identifier Type: -

Identifier Source: org_study_id

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