Novel Treatment Paradigms: Focal Segmental Glomerulosclerosis.
Focal segmental glomerulosclerosis is increasingly understood as a heterogeneous pattern of podocyte injury rather than a single disease, and advances in defining its genetic and immunologic basis — together with intense clinical trial activity and repurposed agents — are opening novel treatment paradigms.
Background
FSGS is a histologic pattern of injury defined by segmental sclerosis in some glomeruli, characterized on electron microscopy by variable podocyte foot process effacement and gaps in glomerular basement membrane coverage. It arises when podocytes — highly differentiated cells with limited regenerative capacity — are reduced in number, and the heterogeneous causes of podocyte loss produce equally variable clinical phenotypes.
Key recommendations
Recent work defining the genetic and immunologic basis of disease has redefined the classification of FSGS, distinguishing primary immune-mediated, genetic, secondary, and undetermined forms. This stratification matters therapeutically, since immunosuppression is appropriate for primary FSGS but potentially harmful in genetic or secondary forms, where strategies targeting the underlying cause, renal hemodynamics, and fibrosis are favoured alongside blood pressure and dietary salt management.
Clinical implications
Unprecedented clinical trial activity and the efficacy of repurposed agents offer hope for improved therapeutic options, with novel approaches targeting the podocyte cytoskeleton and immunologic, inflammatory, hemodynamic, and metabolic pathways. Because therapeutic response remains variable and no agents are specifically approved for FSGS, personalised treatment stratified by clinical, genetic, and histologic data is emerging as the path toward more effective, precision-guided care.
Category
Research
Source
Kidney Int Rep
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