Effects of Lipid Manipulations in Chronic Renal Failure

Summary

Experimental results have demonstrated that a number of effects of hyperlipidemia are involved in the initiation and progression of glomerular injury. First, hyperlipidemia has been associated with the development of progressive mesangial expansion. This expanded mesangium is constituted, in part, by an accumulation of laminin, fibronectin and collagen. These changes in the mesangial region preceded the development of focal glomerulosclerosis (FGS). Similar changes in the mesangium have been observed in clinical and experimental studies, lending credence to the hypothesis that changes in mesangial matrix contribute to the development of FGS. The mechanisms whereby lipid-induced expansion of the mesangial region occur are poorly understood. A second effect of hyperlipidemia is to increase the number of glomerular Ia⁺ macrophages. This influx of macrophages into glomeruli is reminiscent of the influence of hyperlipidemia on macrophage subendothelial localization seen in large vessels during the development of atherosclerosis. Macrophages have also been implicated in glomerular injury in a variety of experimental renal diseases. However, the role that the macrophage or macrophage derived products may play in the development of lipid-induced glomerular injury is at present unknown. Finally, lipid-induced glomerular injury may ultimately lead to altered glomerular hemodynamics, specifically glomerular hypertension, a factor that may contribute to glomerular injury. Indeed, experimental data suggest that an interaction between hypertension and hyperlipidemia may occur, resulting in additive glomerular damage. This interaction between risk factors for glomerular injury may be similar to the interaction between risk factors seen in patients with atherosclerosis.