Apoptosis in the kidneys of patients with type II diabetic nephropathy

Kidney Int. 2007 Nov;72(10):1262-72. doi: 10.1038/sj.ki.5002531. Epub 2007 Sep 12.

Abstract

The occurrence and extent of apoptosis in the kidneys of patients with diabetic nephropathy is largely unknown. We evaluated apoptosis in renal biopsies obtained from patients with early or advanced type II diabetic nephropathy. Apoptosis was about 6- and 3-fold higher, respectively, in glomeruli and tubules in kidneys of patients with early nephropathy than in the normal kidney and this was not further increased in advanced diabetic nephropathy. Glomerular apoptosis was related directly to hemoglobin A1(c) and systolic blood pressure, whereas tubular cell apoptosis correlated to diabetes duration and low-density lipoprotein-cholesterol. Fas, Fas ligand, and p38 mitogen-activated protein kinase expressions were enhanced in glomeruli and tubules; however, this did not correlate with apoptosis. In patients with proteinuria, apoptosis was associated with the subsequent loss of kidney function. When these parameters were subjected to multivariate analysis, only glomerular apoptosis retained a significant independent predictive value. Our findings suggest that apoptosis might be a clinically relevant mechanism of glomerular and tubular cell loss in proteinuric type II diabetic patients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Biopsy
  • Case-Control Studies
  • Cholesterol, LDL / blood
  • Diabetes Mellitus, Type 2 / pathology*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Nephropathies / pathology*
  • Diabetic Nephropathies / physiopathology
  • Fas Ligand Protein / metabolism
  • Glomerular Filtration Rate
  • Glycated Hemoglobin A / analysis
  • Humans
  • Immunohistochemistry
  • Kidney / pathology*
  • Kidney / surgery
  • Kidney Glomerulus / metabolism
  • Kidney Tubules / blood supply
  • Multivariate Analysis
  • Up-Regulation
  • fas Receptor / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Cholesterol, LDL
  • Fas Ligand Protein
  • Glycated Hemoglobin A
  • fas Receptor
  • hemoglobin A1c protein, human
  • p38 Mitogen-Activated Protein Kinases