Podocyte and endothelial injury in focal segmental glomerulosclerosis: an ultrastructural analysis

Podocyte injury contributes to the development of focal segmental glomerulosclerosis (FSGS). Endocapillary hypercellularity, which is one of the pathological characteristics of FSGS, suggests that glomerular endothelial injury may also be involved in the pathogenesis of FSGS. In electron micrographs of patients with FSGS (n = 43), we conducted morphometric measurements of foot process width (FPW) and podocyte detachment (PD) as markers of podocyte injury and subendothelial widening (SW) of the glomerular basement membrane as a marker of endothelial injury and compared them to those in patients with minimal change nephrotic syndrome (MCNS; n = 11) and control kidney donors (n = 5). Associations between ultrastructural and clinical parameters were analyzed according to the FSGS variants defined by the Columbia classification. FPW was significantly higher in the FSGS group than that in the MCNS and control groups, particularly in the collapsing, tip, and cellular variants of FSGS. Percentage of glomerular basement membrane (GBM) length showing PD and SW was significantly increased in the FSGS group, especially in the collapsing, cellular, and not otherwise specified variants. In FSGS, FPW was inversely correlated with disease duration, but not with proteinuria. Finally, the percentage of GBM length with SW significantly correlated with clinical parameters indicative of poor prognosis, such as lower remission rate and lower estimated glomerular filtration rate at the final observation. Quantitative measurement of podocyte and endothelial injury by electron microscopy might be useful for evaluating histological activity and predicting prognosis in FSGS.