STABILITY AND LEAKINESS - OPPOSING CHALLENGES TO THE GLOMERULUS

The complex architecture of the glomerular tuft is stabilized by sever al mechanisms. The basic system consists of the GBM and the mesangium maintaining the branching pattern of the capillary network. Superimpos ed are the podocytes, which appear to take effect by two mechanisms. F irst, podocytes contribute to the stabilization of the capillary foldi ng pattern by supporting the angles between neighboring capillaries. S econd, podocyte foot professes fixed to the outer aspect of the GBM pr obably function as contractile patches counteracting the elastic diste nsion of the GBM. Simultaneously, the pattern of foot process interdig itation underlies the elaboration of a filtration slit and is thus piv otal for the high hydraulic permeability and the specifity of the glom erular filter. The loss of this pattern-commonly termed ''foot process effacement'' or ''foot process fusion''-is frequently found in pathol ogical situations and results in a decrease in permeability and impair ment in specifity. On the other hand, foot process effacement is assoc iated with prominent hypertrophy of the contractile apparatus of podoc ytes, suggesting an increased ability to generate forces counteracting capillary expansion. Thus, foot process effacement appears as an adap tive change in podocyte phenotype giving priority to the support funct ion of podocytes for the prize of reducing the specific permeability.