Novel unbiased assay for circulating podocyte-toxic factors associated with recurrent focal segmental glomerulosclerosis
| Autor: | Martin Bitzan, Paul Goodyer, Sima Babayeva, Elena Torban, Chen-Fang Chung, Erin Benderoff, Nadezda Kachurina, Dany Matar, Andrey V. Cybulsky, Thomas M. Kitzler, Nada Alachkar |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Adult Male Pathology medicine.medical_specialty Adolescent Physiology 030232 urology & nephrology Idiopathic Focal Segmental Glomerulosclerosis urologic and male genital diseases Immunofluorescence Risk Assessment Podocyte 03 medical and health sciences Young Adult 0302 clinical medicine Focal segmental glomerulosclerosis Recurrence medicine Humans Child Cells Cultured Toxins Biological Focal Adhesions medicine.diagnostic_test urogenital system business.industry Glomerulosclerosis Focal Segmental Podocytes Tumor Necrosis Factor-alpha Glomerular basement membrane Glomerulosclerosis Reproducibility of Results Middle Aged medicine.disease female genital diseases and pregnancy complications 3. Good health 030104 developmental biology medicine.anatomical_structure Renal pathology Doxorubicin Child Preschool Immunology Renal allograft Female business |
| Zdroj: | American journal of physiology. Renal physiology. 310(10) |
| ISSN: | 1522-1466 |
| Popis: | Focal segmental glomerular sclerosis (FSGS) is an irreversible renal pathology characterized by podocyte detachment from the glomerular basement membrane, hyalinosis, and sclerosis. Clinically, it manifests with proteinuria and progressive loss of glomerular filtration. Primary idiopathic FSGS can occur in isolation and frequently progresses to end-stage renal disease, requiring dialysis or kidney transplantation. In 30–50% of these patients, proteinuria and FSGS recur in the renal allograft, suggesting the presence of a podocyte-toxic factor(s) in the recipient's serum. Currently, there is no reliable way to quantify the serum activity or predict the subset of FSGS patients at risk for recurrence after transplantation. We describe a novel in vitro method that measures the podocyte-toxic activity of sera from FSGS patients using cultured human podocytes; we compare this with the effect of compounds such as adriamycin. Using immunofluorescence microscopy followed by computerized image-processing analysis, we show that incubation of human podocytes with adriamycin leads to a dose-dependent disassembly of focal adhesion complexes (FACs). We then demonstrate that sera from patients with posttransplant recurrent or idiopathic FSGS cause a similar FAC disturbance. In contrast, sera from nonrecurrent FSGS patients do not affect FACs. In some FSGS patients, toxic effects of serum can be prevented by blockade of the tumor necrosis factor-α pathway. We propose that this method may be useful as a diagnostic tool to identify FSGS patients with serum podocyte-toxic activity that presumably places them at increased risk for recurrence in the renal allograft. |
| Databáze: | OpenAIRE |
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