An observational study in Focal Segmental Glomerulosclerosis, sponsored by Children's Hospital Medical Center, Cincinnati. Completed at 2 sites in United States. Open to participants aged Up to 21 Years. Per ClinicalTrials.gov, last updated 2023-12-21.
Sponsored by Children's Hospital Medical Center, Cincinnati · Observational
Focal segmental glomerulosclerosis (FSGS) is the most common cause of end-stage renal disease (ESRD) in adolescents. The refractory nature of FSGS and a more than 30% recurrence rate after kidney transplantation renders treatment of FSGS one of the most difficult challenges in pediatric nephrology. A significant knowledge gap in understanding the mechanism of FSGS treatment resistance and progression hampers development of successful treatment strategies. Beneficial effect of removal of low-density lipoproteins by LDL-apheresis indicates that lipids contribute to progression in FSGS.
The investigators will test the hypothesis that removal of Lp-PLA2 and lipid metabolites by LDL-apheresis ameliorates proteinuria and cardiovascular comorbidities. Patients with FSGS and FSGS recurrence after kidney transplantation receiving LDL-apheresis as part of standard of care will be enrolled to the study. Pre-and post serum and effluent concentrations of LPC, free FA, Lp-PLA2, oxidized LDL, fasting lipid profile, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β will be monitored in patients undergoing LDL-apheresis. Investigators will also study the impact of LDL-apheresis on cardiovascular and clinical comorbidities by monitoring degree of proteinuria, blood pressures and arterial stiffness index.
Focal segmental glomerulosclerosis (FSGS) is the most common cause of end-stage renal disease (ESRD) in adolescents. The refractory nature of FSGS and a more than 30% recurrence rate after kidney transplantation renders treatment of FSGS one of the most difficult challenges in pediatric nephrology. A significant knowledge gap in understanding the mechanism of FSGS treatment resistance and progression hampers development of successful treatment strategies. Beneficial effect of removal of low-density lipoproteins by LDL-apheresis indicates that lipids contribute to progression in FSGS. We have previously reported increased urinary fatty acids (FA) and lysophosphatidylcholines (LPC) levels with non-targeted urinary lipidomic analysis in children with FSGS. Unregulated phospholipase A2(PLA2) activity causes an increase in intracellular concentrations of free FA and LPC altering plasma membrane and mitochondrial permeability.
Lipoprotein associated PLA2 is a biomarker involved in oxidative modification of LDL by hydrolyzing oxidative lysophosphatidylcholines (LPC) and oxidized free fatty acids (FFA) both of which are proinflammatory and atherogenic. Lp-PLA2 is efficiently removed by LDL-apheresis. The investigators hypothesize that LDL-apheresis ameliorates cellular injury and vascular changes by removing circulating Lp-PLA2, oxidized LDL, LPC, FA and cytokines in FSGS. In this proposal, the hypothesis that removal of Lp-PLA2 and lipid metabolites by LDL-apheresis ameliorates proteinuria and cardiovascular comorbidities will be tested. Patients with FSGS and FSGS recurrence after kidney transplantation receiving LDL-apheresis as part of standard of care will be enrolled to the study. Investigators will monitor pre-and post serum and effluent concentrations of LPC, free FA, Lp-PLA2, oxidized LDL, fasting lipid profile, IL-6, TNF-α, and IL-1β of patients undergoing LDL-apheresis. The impact of LDL-apheresis on cardiovascular and clinical comorbidities by monitoring degree of proteinuria, blood pressures and arterial stiffness index will also be investigated.
The investigators propose that LDL-apheresis as a conjunct therapy to standard treatment regimens is an efficient way to ameliorate progression prevent comorbidities such as systemic inflammation and lipid induced vascular changes thus progression in FSGS. Furthermore, removal of Lp-PLA2 and other lipids by LDL-apheresis can limit the direct toxicity caused by lipid metabolites to podocytes and proximal tubule epithelial cells. The investigators believe that this proposal will enhance understanding of lipid-mediated progression in FSGS and will delineate the role of LDL-apheresis as part of established treatment in treatment of FSGS.
98 studies on the registry are indexed under Glomerulosclerosis, Focal Segmental; 31 are open to participants now.
This study's enrollment of 10 is below the median of 135 across 26 observational studies indexed under Glomerulosclerosis, Focal Segmental.
Browse Glomerulosclerosis, Focal Segmental studies →Children's Hospital Medical Center, Cincinnati is the lead sponsor of 661 studies on the registry; 134 are open to participants now.
Of its 54 completed or terminated interventional studies of FDA-regulated products, 30 (56%) have results posted.
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Pediatric patients with focal segmental glomerulosclerosis (FSGS) in need of LDL-apheresis per standard of care
FSGS and a glomerular filtration rate (GFR) ≥ 60 ml/min/1.73m2 AND
Exclusion Criteria:
Pediatric patients with FSGS requiring LDL-apheresis with the Liposorber
Other: No intervention
No intervention
Severity of Proteinuria
Standard of care proteinuria will be monitored for expected improvement in severity
Time frame: 9 weeks
Cardiovascular comorbidities
LPC, free FA, Lp-PLA2, oxidized LDL, IL-6, TNF-α, and IL-1β will be monitored from patient blood before and after and from the effluent at LDL-apheresis treatments
Time frame: 9 weeks
Plan to share: No
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This study is completed, as verified in Dec 2023. You cannot join it, but the record below documents what was studied.
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Glomerulosclerosis, Focal Segmental→
Children's Hospital Medical Center, Cincinnati