New insights into structural patterns encountered in glomerulosclerosis.
OBJECTIVE
The term 'focal segmental glomerulosclerosis' covers a variety of diseases with different histopathological patterns. There is a need for clues to interpret histological findings in terms of etiology. Studies in transgenic animal models published in recent years have targeted the podocyte with respect to its impact on the development of glomerulosclerosis. Our aim was to survey those models in an attempt to discover correlations between histopathological patterns and pathogenic mechanisms.


RESULTS
The most obvious conclusion to draw from recent studies is that virtually all forms of glomerulosclerosis start with a lesion or dysfunction of podocytes. In hereditary glomerular diseases and transgenic animal models, two patterns of glomerular degeneration may be distinguished. All diseases with late onset appear to follow the 'classic' pathway to focal segmental glomerulosclerosis, starting with an adhesion of the tuft to the Bowman's capsule and eventually leading to nephron degeneration. In contrast, those with early onset frequently exhibit changes that indicate a severe dysregulation of podocyte function resulting in diffuse global endocapillary damage (i.e. mesangial expansion and rarefaction of capillaries).


CONCLUSIONS
Such insights derived from animal models might be useful in elucidating the mechanisms of multifactorial human diseases like diabetic glomerulopathy.
LeHir
Michel
M
Anatomical Institute, University of Zurich, Zurich, Switzerland.
Kriz
Wilhelm
W
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics; D000818:Animals; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics; D003928:Diabetic Nephropathies / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D050199:Podocytes / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D003598:Cytoskeletal Proteins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse