Podocyte Damage and Glomerular Permeability

The renal glomerulus, the site of plasma ultrafiltration and the production of primary urine (1), is the locus of a number of progressive disorders that lead to chronic renal insufficiency. Before the advent of renal replacement therapies, these diseases invariably led to death by uremia. Still, while these treatments save, or at least extend, patient’s lives, they do so at an enormous price, both in human and financial terms. The prevention of chronic renal insufficiency would require therapies that specifically interfere with the pathogenesis of the various underlying glomerular diseases. Disappointingly, however, the molecular mechanisms involved lie in uncharted territory. These conditions can result from varied causes: systemic metabolic disorders, such as diabetes; (auto)immune complex formation, as occurs in membranous and lupus nephropathy; or primary podocyte diseases, such as steroid-sensitive minimal change nephrosis, or the steroid-insensitive condition focal segmental glomerulosclerosis (FSGS).