Podocyte Detachment and Reduced Glomerular Capillary Endothelial Fenestration in Human Type 1 Diabetic Nephropathy
- 1 August 2007
- journal article
- Published by American Diabetes Association in Diabetes
- Vol. 56 (8), 2155-2160
- https://doi.org/10.2337/db07-0019
Abstract
The aim of this study was to investigate the structural characteristics of podocytes and endothelial cells in diabetic nephropathy. We studied 18 patients with type 1 diabetes (seven normoalbuminuric, six microalbuminuric, and five proteinuric), and six normal control subjects. Groups were not different for age. Type 1 diabetic groups were not different for diabetes duration or age at diabetes onset. Podocyte foot process width (FPW), fraction of glomerular basement membrane (GBM) surface with intact nondetached foot processes (IFP), fraction of glomerular capillary luminal surface covered by fenestrated endothelium [SS(Fenestrated/cap)] and classic diabetic glomerulopathy lesions were morphometrically measured. Albumin excretion (AER) and glomerular filtration (GFR) rates were also measured. GFR correlated inversely and AER directly with GBM and mesangial measurements in diabetic patients. FPW correlated inversely with GFR (r = −0.71, P = 0.001) and directly with AER (r = 0.66, P = 0.003), GBM, and mesangial parameters. The GBM fraction covered by IFP was decreased in proteinuric versus control subjects (P = 0.001), normoalbuminuric patients (P = 0.0002) and microalbuminuric patients (P = 0.04) and correlated with renal structural and functional parameters, including AER (r = −0.52, P = 0.03). Only 78% of GBM was covered by IFP in proteinuric patients. SS(Fenestrated/cap) was reduced in normoalbuminuric (P = 0.03), microalbuminuric (P = 0.03), and proteinuric (P = 0.002) patients versus control subjects. SS(Fenestrated/cap) correlated with mesangial fractional volume per glomerulus (r = −0.57, P = 0.01), IFP (r = 0.61, P = 0.007), and FPW (r = −0.58, P = 0.01). These novel studies document that podocyte detachment and diminished endothelial cell fenestration are related to classical diabetic nephropathy lesions and renal function in type 1 diabetic patients and support a need for further studies of podocyte/GBM adherence and podocyte/endothelial cell functional interactions in diabetic nephropathy.Keywords
This publication has 40 references indexed in Scilit:
- Widening of foot processes in normoalbuminuric adolescents with type 1 diabetesPediatric Nephrology, 2005
- Follow-up of kidney biopsies in normoalbuminuric patients with type 1 diabetesPediatric Nephrology, 2004
- Structural alterations to the podocyte are related to proteinuria in type 2 diabetic patientsNephrology Dialysis Transplantation, 2004
- Altering expression of α3β1 integrin on podocytes of human and rats with diabetesLife Sciences, 2000
- Alterations in the expression of the a 3 b 1 integrin in certain membrane domains of the glomerular epithelial cells (podocytes) in diabetes mellitusDiabetologia, 1997
- Participation of endothelial cells in the development of glomerulosclerosis: A study on murine serum sickness nephritis with mitomycin CPathology International, 1996
- Structural-functional relationships in diabetic nephropathy.JCI Insight, 1984
- A solid phase fluorescent immunoassay for the measurement of human urinary albuminKidney International, 1984
- Effect of Alloxan-Induced Diabetes on the Glomerular Filtration Barrier of the RatKidney and Blood Pressure Research, 1980
- Focal glomerular sclerosis in nephrotic patients: An electron microscopic study of glomerular podocytesKidney International, 1975