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Novel unbiased assay for circulating podocyte-toxic factors associated with recurrent focal segmental glomerulosclerosis.
Kachurina, Nadezda; Chung, Chen-Fang; Benderoff, Erin; Babayeva, Sima; Bitzan, Martin; Goodyer, Paul; Kitzler, Thomas; Matar, Dany; Cybulsky, Andrey V; Alachkar, Nada; Torban, Elena.
Afiliación
  • Kachurina N; Department of Medicine, McGill University and McGill University Health Center, Montreal, Quebec, Canada;
  • Chung CF; Department of Medicine, McGill University and McGill University Health Center, Montreal, Quebec, Canada;
  • Benderoff E; Department of Medicine, McGill University and McGill University Health Center, Montreal, Quebec, Canada;
  • Babayeva S; Department of Medicine, McGill University and McGill University Health Center, Montreal, Quebec, Canada;
  • Bitzan M; The Montreal Children's Hospital, Department of Paediatric Nephrology, McGill University Health Center, Montreal, Quebec, Canada;
  • Goodyer P; The Montreal Children's Hospital, Department of Paediatric Nephrology, McGill University Health Center, Montreal, Quebec, Canada; Department of Human Genetics, McGill University, Montreal, Quebec, Canada;
  • Kitzler T; Department of Human Genetics, McGill University, Montreal, Quebec, Canada;
  • Matar D; McKinsey & Company, Washington, District of Columbia; and.
  • Cybulsky AV; Department of Medicine, McGill University and McGill University Health Center, Montreal, Quebec, Canada;
  • Alachkar N; Division of Nephrology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Torban E; Department of Medicine, McGill University and McGill University Health Center, Montreal, Quebec, Canada; elena.torban@mcgill.ca.
Am J Physiol Renal Physiol ; 310(10): F1148-56, 2016 05 15.
Article en En | MEDLINE | ID: mdl-26719363
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Toxinas Biológicas / Glomeruloesclerosis Focal y Segmentaria / Adhesiones Focales / Podocitos Tipo de estudio: Clinical_trials / Etiology_studies / Evaluation_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Physiol Renal Physiol Asunto de la revista: FISIOLOGIA / NEFROLOGIA Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Toxinas Biológicas / Glomeruloesclerosis Focal y Segmentaria / Adhesiones Focales / Podocitos Tipo de estudio: Clinical_trials / Etiology_studies / Evaluation_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Physiol Renal Physiol Asunto de la revista: FISIOLOGIA / NEFROLOGIA Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos