Figure 1.

Simplified version of renal changes caused by hyperfiltration followed by lower filtration.Middle: Initially, glomerular filtration rate increases (hyperfiltration), followed by a decrease in GFR and CKD leading to ESRD. Left: Increased fluid flow shear stress drives effects of hyperfiltration in the early stages indicated by glomerular/podocyte dysfunction. Gradual increase in tensile stress is associated with rapid loss of glomerular function and tubular changes causing CKD. Right: Cellular stress causes inflammatory changes and the release of fatty acids from membrane phospholipids. Fatty acid metabolites mediate mechanotransduction and activate cellular signaling pathways as an initial response to hyperfiltration. With time, tubular homeostasis also changes in response to early glomerular changes. Initial lipid-mediated signaling events are followed by more complex and diverse signaling and functional changes resulting in albuminuria, matrix accumulation, fibrogenesis, podocyte loss leading to glomerulosclerosis and fibrosis.