A novel assay provides sensitive measurement of physiologically relevant changes in albumin permeability in isolated human and rodent glomeruli

Sara Desideri, Karen L. Onions, Yan Qiu, Raina D. Ramnath, Matthew J. Butler, Christopher R. Neal, Matthew L.R. King, Andrew E. Salmon, Moin A. Saleem, Gavin I. Welsh, C. Charles Michel, Simon C. Satchell, Andrew H.J. Salmon, Rebecca R. Foster*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

16 Citations (Scopus)
155 Downloads (Pure)

Abstract

Increased urinary albumin excretion is a key feature of glomerular disease but has limitations as a measure of glomerular permeability. Here we describe a novel assay to measure the apparent albumin permeability of single capillaries in glomeruli, isolated from perfused kidneys cleared of red blood cells. The rate of decline of the albumin concentration within the capillary lumen was quantified using confocal microscopy and used to calculate apparent permeability. The assay was extensively validated and provided robust, reproducible estimates of glomerular albumin permeability. These values were comparable with previous in vivo data, showing this assay could be applied to human as well as rodent glomeruli. To confirm this, we showed that targeted endothelial glycocalyx disruption resulted in increased glomerular albumin permeability in mice. Furthermore, incubation with plasma from patients with post-transplant recurrence of nephrotic syndrome increased albumin permeability in rat glomeruli compared to remission plasma. Finally, in glomeruli isolated from rats with early diabetes there was a significant increase in albumin permeability and loss of endothelial glycocalyx, both of which were ameliorated by angiopoietin-1. Thus, a glomerular permeability assay, producing physiologically relevant values with sufficient sensitivity to measure changes in glomerular permeability and independent of tubular function, was developed and validated. This assay significantly advances the ability to study biology and disease in rodent and human glomeruli.

Original languageEnglish
Pages (from-to)1086-1097
Number of pages12
JournalKidney International
Volume93
Issue number5
Early online date9 Feb 2018
DOIs
Publication statusPublished - 1 May 2018

Keywords

  • albuminuria
  • angiopoietin-1
  • diabetes
  • endothelial glycocalyx
  • glomerular permeability
  • steroid-resistant nephrotic syndrome plasma

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