Abstract: Glomerular endothelial dysfunction is believed to be responsible for the proteinuria and nephronal damage, namely tubulointerstitial fibrosis and glomerulosclerosis, observed in severe nephrosis such as focal segmental glomerulosclerosis. A dysfunctioning glomerular endothelium is likely to be induced by oxidative stress and oxidized LDL as well as altered immunocirculatory balance with a defective anti‐inflammatory pathway. A defective release of vasodilator inconjunction with enhanced production of angiotensin II induces hemodynamic maladjustment by preferential constriction at the efferent arteriole. Such a hemodynamic maladjustment exerts two significant hemodynamic impacts. Close to the efferent constriction, it induces intraglomerular hypertension and glomerulosclerosis. Far from the efferent constriction, it reduces peritubular capillary flow, which eventually leads to tubulointerstitial fibrosis. Treatment with a vasodilator improves the hemodynamic maladjustment but does not completely suppress proteinuria. A successful suppression of proteinuria is accomplished by using Ganoderma lucidum and vitamins C and E. The beneficial effect of Ganoderma lucidum appears to be multifactorial, including the modulation of immunocirculatory balance, antilipid, vasodilator, antiplatelet and improved hemorheology. Together with vitamins C and E, this helps to neutralize oxidative stress and suppress the toxic effect to the glomerular endothelial function.
