Novel unbiased assay for circulating podocyte-toxic factors associated with recurrent focal segmental glomerulosclerosis

Nadezda Kachurina, Chen Fang Chung, Erin Benderoff, Sima Babayeva, Martin Bitzan, Paul Goodyer, Thomas Kitzler, Dany Matar, Andrey V. Cybulsky, Nada Alachkar, Elena Torban

Research output: Contribution to journalArticlepeer-review

Abstract

Focal seg-mental 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 micros-copy 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.

Original languageEnglish (US)
Pages (from-to)F1148-F1156
JournalAmerican Journal of Physiology - Renal Physiology
Volume310
Issue number10
DOIs
StatePublished - May 15 2016

Keywords

  • Idiopathic focal segmental glomerulosclerosis
  • Renal allograft

ASJC Scopus subject areas

  • Physiology
  • Urology

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