Podocyte Detachment and Reduced Glomerular Capillary Endothelial Fenestration Promote Kidney Disease in Type 2 Diabetic Nephropathy

Kidney Int. 2012 Nov;82(9):1010-7. doi: 10.1038/ki.2012.234. Epub 2012 Jun 20.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00340678.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuminuria / drug therapy
  • Albuminuria / pathology
  • Antihypertensive Agents / administration & dosage
  • Biopsy
  • Capillaries / pathology
  • Capillaries / ultrastructure
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / pathology*
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / pathology*
  • Endothelial Cells / pathology
  • Endothelial Cells / ultrastructure
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Indians, North American
  • Kidney Glomerulus / blood supply
  • Kidney Glomerulus / pathology*
  • Kidney Glomerulus / ultrastructure
  • Losartan / administration & dosage*
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Podocytes / pathology*
  • Podocytes / ultrastructure

Substances

  • Antihypertensive Agents
  • Losartan

Associated data

  • ClinicalTrials.gov/NCT00340678