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Abstract: SA-PO906

Low-Density Lipoprotein (LDL) Apheresis Removes Atherogenic Mediators in Focal Segmental Glomerulosclerosis

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Humphrey, Jacob A., Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Rose, James, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Krallman, Kelli A., Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Zaritsky, Joshua, Phoenix Children's Hospital, Phoenix, Arizona, United States
  • Moritz, Michael L., Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States
  • Goldstein, Stuart, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Erkan, Elif, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
Background

Focal Segmental Glomerulosclerosis (FSGS) is the most common cause of end stage kidney disease in adolescents. Lipid dysregulation causes cardiovascular morbidity and disease progression in FSGS. Unregulated lipoprotein associated phospholipase A2 (Lp-PLA2) activity causes increased oxidation of low-density lipoprotein (oxLDL) and production of inflammatory cytokines, leading to atherosclerosis and poor cardiovascular outcomes. However, this has not been explored in children with FSGS. We hypothesize that LDL apheresis can improve cardiovascular outcomes by removal of atherogenic mediators in patients with FSGS.

Methods

We enrolled 10 patients with FSGS from 4 centers (mean age 15.3 years, M/F: 6/4). Five patients had post-transplant FSGS recurrence. Patients received 12 LDL apheresis treatments via the Liposorber in addition to standard immune therapies. Atherogenic lipid metabolites (Lp-PLA2, oxLDL) and cytokines (TNFα, IL-6, IL-1β) were collected pre and post-treatment at set intervals and measured via ELISA. Proteinuria was measured by urine protein to creatinine ratio (UPC) and cystatin C GFR was monitored pre and at the completion of LDL apheresis treatment. Results expressed as mean±SEM.

Results

OxLDL was reduced from 94.7 ± 15.3 to 78.6 ± 11.4 u/L (p=0.019) at the completion of LDL apheresis. Lp-PLA2 showed a trend of reduction from 173.6 ± 36.8 to 117.9 ± 15.7 ng/mL (p=0.07). Interestingly, the mean baseline ox-LDL levels were significantly elevated, comparable to patients with extreme obesity. UPC was reduced from 10.3 ± 2.5 to 5.7 ± 1.8 mg/mg (p=0.005). Mean cystatin C GFR was 57mL/min at baseline and was unchanged over the study period.

Conclusion

We demonstrated that children and adolescents with FSGS have elevated levels OxLDL and Lp-PLA2, increasing the risk for long term atherogenesis and cardiovascular morbidity. We propose that monitoring and normalizing these lipid metabolites will promote cardiovascular health in patients with FSGS. LDL apheresis remains a safe and effective method of reducing oxLDL and Lp-PLA2 in patients with FSGS. This was accompanied by a significant reduction in proteinuria inducing disease remission. Larger studies are needed to further assess the effects of LDL apheresis and antilipidemic treatments on cardiovascular outcomes in this patient population.

Funding

  • Commercial Support – Kaneka Medical America LLC