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2018 ; 93
(5
): 1086-1097
Nephropedia Template TP
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English Wikipedia
A novel assay provides sensitive measurement of physiologically relevant changes
in albumin permeability in isolated human and rodent glomeruli
#MMPMID29433915
Desideri S
; Onions KL
; Qiu Y
; Ramnath RD
; Butler MJ
; Neal CR
; King MLR
; Salmon AE
; Saleem MA
; Welsh GI
; Michel CC
; Satchell SC
; Salmon AHJ
; Foster RR
Kidney Int
2018[May]; 93
(5
): 1086-1097
PMID29433915
show ga
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.