Glomerulosclerosis: pathogenetic mechanisms and possibility of regression

Glomerular sclerosis means an increase in the extracellular matrix of the glomerulus. It is a complex, heterogeneous phenomenon with multiple cellular and biochemical mechanisms and different morphological patterns, depending on a variety of local and systemic factors. The term as such does not indicate the quantity nor the type of components of the deposited matrix. The amount of extracellular matrix increases in three types of events: - matrix deposition in areas that were destroyed by a necrotizing process (scars following glomerular necrosis); - matrix deposition in glomerular regions where matrix is normally found (mesangium, glomerular basement membranes) as seen in diabetic nephropathy; - matrix deposition inside or around collapsing capillaries involving the entire glomerulus or a segment of it (focal segmental glomerular sclerosis with nephrotic syndrome). Knowledge of the diverse morphological patterns producing glomerular sclerosis and the cellular and molecular mechanisms involved is essential for obvious reasons: they represent the rationale for any therapy aimed at preventing or reducing the progression of sclerosis and can provide a starting point to determine which forms are, at least potentially, reversible.