Podocyte detachment and reduced glomerular capillary endothelial fenestration promote kidney disease in type 2 diabetic nephropathy.
Podocyte detachment and reduced endothelial cell fenestration and relationships between these features and the classic structural changes of diabetic nephropathy have not been described in patients with type 2 diabetes. Here we studied these relationships in 37 Pima Indians with type 2 diabetes of whom 11 had normal albuminuria, 16 had microalbuminuria, and 10 had macroalbuminuria. Biopsies from 10 kidney donors (not American Indians) showed almost undetectable (0.03%) podocyte detachment and 43.5% endothelial cell fenestration. In patients with type 2 diabetes, by comparison, the mean percentage of podocyte detachment was significantly higher in macroalbuminuria (1.48%) than in normal albuminuria (0.41%) or microalbuminuria (0.37%). Podocyte detachment correlated significantly with podocyte number per glomerulus and albuminuria. The mean percentage of endothelial cell fenestration was significantly lower in macroalbuminuria (19.3%) than in normal albuminuria (27.4%) or microalbuminuria (27.2%) and correlated significantly with glomerular basement membrane thickness, albuminuria, fractional mesangial area, and the glomerular filtration rate (iothalamate clearance). Podocyte detachment and diminished endothelial cell fenestration were not correlated, but were related to classic lesions of diabetic nephropathy. Thus, our findings confirm the important role these injuries play in the development and progression of kidney disease in type 2 diabetes, just as they do in type 1 diabetes. Whether podocyte detachment creates conduits for proteins to escape the glomerular circulation and reduced endothelial fenestration lowers glomerular hydraulic permeability requires further study.
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85014-4972, USA. rnelson@nih.gov
E Jennifer
EJ
Weil
Kevin V
KV
Lemley
Clinton C
CC
Mason
Berne
B
Yee
Lois I
LI
Jones
Kristina
K
Blouch
Tracy
T
Lovato
Meghan
M
Richardson
Bryan D
BD
Myers
Robert G
RG
Nelson
D000328:Adult; D000419:Albuminuria / Q000188:drug therapy / Q000473:pathology; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001706:Biopsy; D002196:Capillaries / Q000473:pathology / Q000648:ultrastructure; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology*; D042783:Endothelial Cells / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007198:Indians, North American; D007678:Kidney Glomerulus / Q000098:blood supply / Q000473:pathology* / Q000648:ultrastructure; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D050199:Podocytes / Q000473:pathology* / Q000648:ultrastructure
D000959:Antihypertensive Agents; D019808:Losartan