Experimental models have established a role for lipoproteins in the pathogenesis of progressive renal failure. However, conventional treatment rarely normalizes the high serum cholesterol of the nephrotic syndrome. The removal of low-density lipoprotein by lipopheresis is discussed.Lipopheresis may be beneficial in nephrotic patients with focal segmental glomerulosclerosis. The authors studied the long-term effects of low-density lipoprotein cholesterol (LDL-C) removal using the Kaneka Liposorber system, which binds LDL-C to dextran sulfate in a controlled trial in 20 nephrotic patients with different renal diseases.A 21-month clamp of plasma total cholesterol at 6.0 mmol/liter or below was significantly lower than controls (chi 2 = 84.3, P < 0.001), followed 12 aphereses over 6 to 12 weeks in all but three apheresed patients. 1/Cr slopes were unchanged when the 50-day average period of lipopheresis treatments was excluded from analysis. Proteinuria was not reduced, but serum albumin tended to rise (NS). Fibrinogen fell by 29.8%; high-density lipoprotein, apoA1, and Lp(a) were unchanged. Two apheresed patients had a prolonged remission with a reduction of proteinuria to less than 250 mg/24 hr. The reasons for prolonged reduction of total cholesterol include depletion of tissue cholesterol, an improved fractional catabolic rate of very low density lipoprotein (VLDL), increased hepatocyte LDL turnover, and the maintenance of statin therapy.Lipopheresis is a safe and effective method for the control of LDL in nephrotic syndrome. Early clamping of total cholesterol in the normal range resulted in a prolonged and significant reduction of LDL compared with controls.