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Abstract: SA-PO381

Beneficial Effect of Low-Density Lipoprotein Apheresis via Modifying Immune System in Patients with Refractory Nephrotic Syndrome

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Kakita, Hiroko, Tazuke Kofukai Foundation, Medical Research Institute, Kitano Hospital, Osaka, Japan
  • Suzuki, Hiroyuki, Tazuke Kofukai Foundation, Medical Research Institute, Kitano Hospital, Osaka, Japan
  • Tsukamoto, Tatsuo, Tazuke Kofukai Foundation, Medical Research Institute, Kitano Hospital, Osaka, Japan
  • Muso, Eri, Tazuke Kofukai Foundation, Medical Research Institute, Kitano Hospital, Osaka, Japan
Background

In refractory nephrotic syndrome (rNS), in addition to direct injury of heavy proteinuria, longstanding hypercholesterolemia is known to provide poor renal outcome. The amelioration of dyslipidemia by low-density lipoprotein apheresis (LDL-A) in combination with conventional therapy was reported to induce rapid remission of NS primarily in focal segmental glomerulosclerosis (FSGS) and evidence of these beneficial effect has additionally accumulated in minimal change nephrotic syndrome (MCNS) and membranous nephropathy (MN). As the mechanism of action, in addition to the renal protection by rapid removal of low-density lipoprotein cholesterol (LDL-C), LDL-A has been proved to provide amelioration of macrophage dysfunction, restore steroid and cyclosporine susceptibility and adsorption of circulating permeability factors. To investigate immune-modulatory effect, we measured serum cytokines and chemokines level before and after LDL-A in a patient of FSGS and compared with familial hypercholesterolemia (FH) and reported significant and specific increase of Interleukin-10 (IL-10) after LDL-A in rNS, but not in FH. In the present study, in order to obtain more precise elucidation of immunological effect and disease specificity of LDL-A, the changes of not only serum but peripheral blood mononuclear cell (PBMC) cytoplasmic cytokines in patients with FSGS, MCNS and MN were evaluated.

Methods

Serum cytokines level before and after LDL-A sessions was assessed in three cases of rNS due to FSGS (6 sessions), MCNS (12) and MN (4), and compared with a non-NS, arteriosclerosis obliterans (ASO) patient treated by LDL-A (5 sessions). 27 types of cytokines were measured by Bio-Plex Pro human 27-plex kit (Bio-Rad). Cytoplasmic cytokines among PBMC were evaluated by flow cytometry.

Results

IL-10 was significantly elevated after LDL-A in all NS patients (p=7.2x10-5). In ASO, IL-10 was not detected in sera before nor after LDL-A. Cytoplasmic IL-10 was positive in CD19+CD5+ cells, CD19-CD5-cells and CD19-CD5+cells. In addition, another anti-inflammatory cytokine, IL-1 receptor antagonist (IL-1Ra) was significantly elevated after LDL-A (p<0.002) in both NS and ASO.

Conclusion

LDL-A may induce rapid remission in rNS patients, via immunomodulation by session synchronized elevation of IL-1Ra and IL-10 regardless of causative disease.

Funding

  • Commercial Support