HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Diabetic nephropathy, inflammation, hyaluronan and interstitial fibrosis

Aled Lewis1, Robert Steadman1, Paul Manley1, Kathrine Craig1, Carol de la Motte2, Vincent Hascall3 and Aled O. Phillips1

1Institute of Nephrology, University of Wales College of Medicine, Cardiff, Wales, UK, Departments of 2Colorectal Surgery and 3Biomedical Engineering, The Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Offprint requests to: Prof A.O. Phillips, Institute of Nephrology, University of Cardiff School of Medicine, Heath Park, Cardiff CF14 4XN, UK. e-mail: PhillipsAO@cf.ac.uk


Summary. 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 non-progressors. 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 I
αI compared to the normal controls and there was a significant correlation between interstitial HA and IαI.
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
. Histol Histopathol 23, 731-739 (2008)

Key words: Diabetic nephropathy, Hyaluronan, Macrophages, Interstitial fibrosis

DOI: 10.14670/HH-23.731