Purpose of review: Focal segmental glomerulosclerosis (FSGS) is a disease with diverse histologic patterns and etiologic associations. Genetic, toxic, infectious and inflammatory mediators have been identified. This review will focus on new evidence supporting the potential mechanistic basis underlying the histologic variants and their clinical relevance.
Recent findings: Evidence from animal models and in-vitro studies suggests that injury inherent within or directed to the podocyte is a central pathogenetic factor. Disruption of signaling from any of the podocyte's specialized membrane domains, including slit diaphragm, apical and basal membranes, or originating at the level of the actin cytoskeleton, may promote the characteristic response of foot process effacement. Irreversible podocyte stress leading to podocyte depletion through apoptosis or detachment is a critical mechanism in most forms of FSGS. In the collapsing variant, podocyte dysregulation leads to podocyte dedifferentiation and glomerular epithelial cell proliferation.
Summary: Translation studies in humans and new evidence from animal models have provided mechanistic insights into the diverse phenotypes of FSGS.