LDL, particularly P505-15 cost oxidized LDL, is incorporated by mesangial cells with scavenger receptors, forming foam cells. The foam cells and induced macrophages express various inflammatory cytokines and chemokines and cause tissue damage (Fig. 1) [2]. In addition, a large amount of protein leaks into the urine, but detached tubular cells that

have absorbed fat are often observed. These reabsorbed excess lipids are considered to damage tissues by intensifying GF120918 concentration oxidative stress in the renal tubules [3]. Typical findings such as the frequent appearance of interstitial foam cells are observed in FSGS, in which dyslipidemia persists. Fig. 1 Lipid nephrotoxicity Anti-nephropathic effect of the correction of hyperlipidemia associated with nephrotic syndrome The secondary dyslipidemia mentioned above can be corrected by statins over a long period, but by LDL-A if an acute effect is expected. In LDL-A using a dextran sulfate column (Liposorber, Kaneka), which is prepared by coating porous Sepharose beads with dextran sulfate, LDL-cholesterol is adsorbed due to an electrostatic interaction between negatively charged dextran sulfate and positively charged apoprotein

B on the surface of lipoprotein. VLDL and LDL are selectively adsorbed, but no HDL-cholesterol with ApoA or other plasma components including albumin is adsorbed. Liposorber can purify 3–4,000 ml of plasma in 2–3 h. When Sakai et al. first carried out this treatment many for FSGS in 1988 in Japan, not only the click here correction of hyperlipidemia, but also rapid resolution of NS was observed, so coverage by national health insurance was extended to its application to FSGS with hyperlipidemia (LDL-cholesterol >250 mg/dl) in 1989. Evaluation of the mechanism of the effects of LDL-A (Table 1) Effects of adsorption of LDL, particularly oxidized LDL

The infiltration of lesions by macrophages induces cytokines and chemokines such as TNFα and IL-8, which are elevated in the serum of nephrotic patients, and causes inflammation and the activation of mesangial cells. LDL scavenger receptors present in these macrophages are likely to be hyperstimulated by an increase in LDL-cholesterol, particularly oxidized LDL, in the circulation. Evaluation of the effect of LDL-A on LPS-stimulated IL-8 production by peripheral monocytes by its comparison between before and after treatment revealed significant suppression of the responsiveness compared with that in healthy subjects before treatment, but this was significantly recovered after treatment [6]. This is considered to have been due to the recovery of macrophage function caused by the rapid elimination of LDL. Table 1 Hypothetical mechanism of action of LDL-A on refractory NS 1. Direct effect of lipid (LDL, VLDL, oxLDL) adsorption (1) Reduction of macrophage stimulation by ox-LDL (2) Amelioration of macrophage dysfunction (3) Reduction of inflammatory cytokine 2.