Pathophysiology of focal segmental glomerulosclerosis

Abstract

Focal segmental glomerulosclerosis (FSGS) is a major cause of idiopathic steroid-resistant nephrotic syndrome (SRNS) and end-stage kidney disease (ESKD). In recent years, animal models and studies of familial forms of nephrotic syndrome helped elucidate some mechanisms of podocyte injury and disease progression in FSGS. This article reviews some of the experimental and clinical data on the pathophysiology of FSGS.

Fig. 1

A Components of the normal glomerular filtration barrier: (1) glomerular basement membrane (GBM); (2) podocyte foot process; (3) endothelial cell; B Progressive changes seen in focal segmental glomerulosclerosis (FSGS) leading to sclerosis: (1) foot process effacement; (2) podocyte apoptosis/loss and exposed glomerular basement membrane; (3) filtration of non-specific plasma proteins; (4) capillary expansion; (5) formation of synechiae; (6) misdirected filtration at points of synechiae; (7) mesangial matrix proliferation. Adapted from Kwoh et al. [9]

Fig. 2

Factors involved in the progression of FSGS to end-stage kidney disease (ESKD): initial loss or injury to podocytes (related to defects in membrane proteins or cytoskeleton instability) leads to cytokine release, mechanical stress, hyperfiltration, and glomerular hypertrophy. These factors lead to upregulation of an inflammatory response mediated by monocytes, macrophages, and T-cells. The end result is collagen matrix deposition and fibrosis, and progression to ESKD