Publication: Diabetic nephropathy inflammation, hyaluronan and interstitial fibrosis
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Date
2008
Authors
Lewis, Aled ; Steadman, Robert ; Manley, Paul ; Craig, Kathrine ; Motte, Carol de la ; Hascall, Vicent ; Phillips, Aled O.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Hyaluronan (HA) is a ubiquitous connective
tissue glycosaminoglycan component of most
extracellular matrices and alterations in its synthesis
have been suggested to be involved in the glomerular
changes of diabetic nephropathy. Similarly it has been
suggested that macrophages are involved in the initiation
of diabetic glomerular injury. Much less is known
regarding the role of the prognostic value of changes in
interstitial HA and interstitial inflammatory infiltrate.
The aim of this study was to examine the potential
association of inflammatory infiltrate, deposition of the
matrix component hyaluronan and inter-alpha inhibitor
(which is involved in HA assembly) and clinical
outcome in diabetic nephropathy.
Histological specimens of 40 patients with biopsy
proven diabetic nephropathy were examined. Based on
the rate of change in estimated GFR (eGFR, abbreviated
MDRD formula), patients were defined as late
presenters, progressors or non-progressors.
The degree of interstitial fibrosis was associated
with progression of disease and late presentation. There
was a significant greater number of CD68-positive cells
in the interstitium of patients who subsequently
developed progressive renal disease, or those who
presented with advanced disease compared to nonprogressors.
In contrast, there was significant staining
for interstitial HA in all the patient groups. Furthermore
there was no correlation between the accumulation of
HA and CD68-positive macrophages. In addition all
patients with biopsy-proven diabetic nephropathy had
significantly greater interstitial IaI compared to the
normal controls and there was a significant correlation
between interstitial HA and IaI.
Increased HA is seen at all stages of diabetic change
in the kidney but is not predictive of progression.
Macrophage influx, however, is directly related to the progression of diabetic nephropathy and is not
associated with HA accumulation.
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