Focal and segmental glomerulosclerosis: Analogies to atherosclerosis

Abstract

In summary, both the developing atherosclerotic and FSGS lesions seem to share certain postulated pathophysiologic mechanisms, including endothelial cell injury, macrophage infiltration, hyperlipoproteinemia, and hypertension. As depicted in Figure 1, any initial glomerular injury results in flux of macromolecular substances into the glomerular mesangium. As an adjunct to increased glomerular barrier dysfunction, hyperlipoproteinemia is believed to secondarily develop from the dramatic losses of albumin, stimulating increased hepatic lipoprotein synthesis and the loss of lipoprotein lipase-activating substance into the urine which would effectively produce a reduction in circulating chylomicra and triglyceride catabolism. Certain elevated circulating lipoproteins could, theoretically, pass through the damaged glomerular filter into the mesangium, thereby enhancing the flux of macromolecules. Also associated with certain experimental glomerular disorders is the development of glomerular hypertension, as manifested by an elevated glomerular capillary hydrostatic pressure (PGC), which can further augment macromolecular flux into the mesangium. Overloading of the glomerular mesangium by the above mechanisms is believed to be an injurious stimulus for MC to both proliferate and produce excess mesangial matrix substance. Both of these events are thought to be pathologic harbingers of glomerulosclerosis. Glomerular hypertension is also capable of damaging endothelial cells within th…