How does podocyte damage result in tubular damage?

Severe podocyte damage including detachment from the GEM leads to adhesion of the glomerular tuft to Bowman's capsule, thus to a local loss of the sep aration of the tuft from the interstitium. Perfused capillaries contained i n the tuft adhesion deliver their filtrate no longer into Bowman's space bu t into the interstitium. In response, interstitial fibroblasts create a cel lular cover around the focus of misdirected filtration, interpreted teleolo gically, aiming at preventing the entry of this fluid into the interstitium . This results in the formation of a crescent-shaped, fluid-filled paraglom erular space over-arching the segmental glomerular lesion. Extension of thi s space over the entire glomerulus leads to global sclerosis; extension of this space via the urinary pole onto the outer aspect of the corresponding tubule leads to the degeneration of the tubule. Since, as we postulate, suc h misdirected filtration and filtrate spreading is the crucial mechanism of damage progression in 'classic' focal segmental glomerulosclerosis (FSGS), the most characteristic structural injury of FSGS is the merger of the tuf t with the interstitium, represented by a tuft adhesion, later a synechia. Therefore, histopathologically, 'classic' FSGS is best defined by an adhesi on/synechia of the tuft to Bowman's capsule.