Fellow 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 and remains one of the most challenging conditions to treat in pediatric nephrology. Up to 30-40 percent of patients can have FSGS recurrence following kidney transplantation. A consequence of FSGS is lipid dysregulation, which causes cardiovascular morbidity and progression of renal disease in these patients. Unregulated lipoprotein associated phospholipase A2 (Lp-PLA2) activity causes increased oxidation of low-density lipoprotein (oxLDL) and production of inflammatory cytokines which in turn leads to atherosclerosis and poor cardiovascular outcomes. This connection has not been thoroughly explored in children with FSGS. Objective: We hypothesize that children with FSGS are at risk for atherosclerosis due to circulating atherogenic mediators and that LDL apheresis can remove these mediators. We are also examining the cytotoxic effects of lipid dysregulation by incubating human podocytes with effluent from the LDL apheresis treatments. Design/Methods: We enrolled 10 patients with FSGS from 4 different centers. The mean age was 15.3 years and 6/10 patients were male. There were 5 patients with FSGS recurrence after transplant. Patients received 12 LDL apheresis treatments with the Kaneka Liposorber; 2 treatments per week for 3 weeks, then 1 treatment per week for 6 weeks. All patients received standard immune therapies per their primary nephrologist. Atherogenic metabolites (such as Lp-PLA2 and oxLDL) and cytokines (such as TNFa, IL-6, and IL-1B) were collected pre- and post-treatment at set intervals. These metabolites and cytokines were measured via ELISA per standard methods as provided by the manufacturers (R&D Systems and Mercodia). Clinical data was collected including urine protein to creatinine ratio and cystatin C eGFR. Effluent samples were collected and frozen. Immortalized human podocytes were incubated with varying concentrations of effluent from the LDL apheresis treatments. Cell were then lysed and will be western blotted for structural proteins.
