Towards a biological characterization of focal segmental glomerulosclerosis

The primary form of focal segmental glomerulosclerosis (FSGS) has become one of the most common causes of end-stage renal disease in children and adolescents. FSGS was initially considered to be the histological expression of a single disease entity. However, evidence accumulated during the past four decades indicates that FSGS is heterogeneous in nature. It therefore is not surprising that the many therapeutic combinations and permutations that have been tried have yielded variable results in different hands. This has generated substantial confusion and frustration among physicians and patients alike. Recent progress in genetics and molecular biology has opened promising new vistas of investigation. Identification of genes that control components of the glomerular capillary, proteins that form the structural basis of podocytes, and genetic mutations that affect the integrity of these structures has revolutionized our understanding of the glomerular filtration barrier. Substantial progress also has been made in understanding the mechanisms that lead to progression of renal disease and, ultimately, sclerosis. Studies of these factors are likely to yield a mechanistic-based classification of FSGS that will allow us to design therapeutic regimens suited to specific subtypes of this disease.