The pathogenesis of 'classic' focal segmental glomerulosclerosis-lessons from rat models

The present paper summarizes the evidence for the hypothesis that the development of focal segmental glomerulosclerosis (FSGS-'classic' type) is initiated and maintained by injury to podocytes. Loss of podocytes leads to the formation of tuft adhesions to Bowman's capsule, followed-with a certain probability-by misdirected filtration. This leads to a sequence of events resulting in degeneration of the entire nephron. The way by which the nephron undergoes destruction in this process assures that the destructive effects remain confined to the initially affected nephron. There is no nephron-to-nephron transfer of the disease at the level of the tubular interstitium.