Advances in the biology and genetics of the podocytopathies: implications for diagnosis and therapy

Arch Pathol Lab Med. 2009 Feb;133(2):201-16. doi: 10.5858/133.2.201.

Abstract

Context: Etiologic factors and pathways leading to altered podocyte phenotype are clearly numerous and involve the activity of different cellular function.

Objective: To focus on recent discoveries in podocyte biology and genetics and their relevance to these human glomerular diseases, named podocytopathies.

Data sources: Genetic mutations in genes encoding for proteins in the nucleus, slit diaphragm, podocyte cytoplasm, and cell membrane are responsible for podocyte phenotype and functional abnormalities. Podocyte injury may also derive from secondary stimuli, such as mechanical stress, infections, or use of certain medications. Podocytes can respond to injury in a limited number of ways, which include (1) effacement, (2) apoptosis, (3) arrest of development, and (4) dedifferentiation. Each of these pathways results in a specific glomerular morphology: minimal change nephropathy, focal segmental glomerulosclerosis, diffuse mesangial sclerosis, and collapsing glomerulopathy.

Conclusions: Based on current knowledge of podocyte biology, we organized etiologic factors and morphologic features in a taxonomy of podocytopathies, which provides a novel approach to the classification of these diseases. Current and experimental therapeutic approaches are also discussed.

MeSH terms

  • Apoptosis / drug effects
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Humans
  • Kidney Diseases / diagnosis
  • Kidney Diseases / genetics*
  • Kidney Diseases / pathology*
  • Mutation / genetics
  • Podocytes / drug effects
  • Podocytes / pathology*