Abstract: SA-PO222
LDL Lipidome and Erythropoiesis Stimulating Agent Response in Hemodialysis Patients
Session Information
- Anemia and Iron Metabolism: Basic
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Anemia and Iron Metabolism
- 201 Anemia and Iron Metabolism: Basic
Authors
- Risinger, Will, University of Louisville School of Medicine, Louisville, Kentucky, United States
- Perkins, Jordan T., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Wilkey, Daniel Wade, University of Louisville Kidney Disease Program, Louisville, Kentucky, United States
- Rovin, Brad H., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Himmelfarb, Jonathan, Kidney Research Institute, Seattle, Washington, United States
- Jacobs, Alfred A., University of Louisville, Louisville, Kentucky, United States
- Klein, Jon B., University of Louisville Kidney Disease Program, Louisville, Kentucky, United States
- Brier, Michael E., University of Louisville Kidney Disease Program, Louisville, Kentucky, United States
- Merchant, Michael, University of Louisville Kidney Disease Program, Louisville, Kentucky, United States
Background
Anemia management in end-stage renal disease (ESRD) is difficult due to variable erythropoiesis stimulating agent (ESA) response. Hemodialysis alters lipoprotein composition. Additionally in-vitro erythropoietic burst assays respond to changes in lipoprotein supplementation; suggesting a role in RBC formation. We have previously shown HDL proteome differs with ESA response in maintenance hemodialysis (HD) patients. We hypothesized HD patients ESA response was associated with HDL/LDL composition.
Methods
HDL & LDL were isolated by dextran sulfate precipitation (n=105 patient samples). Purity was assessed by immunoblot and proteomics. Total cholesterol (Cho), phospholipid (PL) and triacylglycerol (TAG) were quantified by enzyme assay. Avanti SPLASH™ LipidoMix® standards were added before Bligh-Dyer LDL lipid extraction. LCMS analysis and informatics used Waters UPLC-Synapt G2-Si Q-Tof MSe (+/- ion modes) with Progenesis QI + LipidMAPS database. Data were normalized to internal spike-in and total Cho; results filtered based on mass accuracy (<15ppm), fragmentation score, and isotopic matching. Categorical differences (ESA naïve (38), ESA hyper (23)-, ESA normal (22)-, and ESA hypo-(22) responders) were compared by ANOVA, and continuous differences with Spearman correlation.
Results
LDL Cho but not HDL Cho was negatively correlated (p<0.05) with ESA utlization. Lipidomics identified 222 LDL-associated lipids including 36 different by ANOVA (p<0.05)- 22 increased and 3 decreased with EPO-dose response groupings; 11 lipids changed with EPO use relative to EPO naïve patients. Post-hoc ttest shows significant increase of four lipids (hyper-to-hypo-EPO response) including a cholesterol ester, ceramide, and a vitamin D3 analogue. Spearman analysis revealed LDL-lipid correlation to EPO dose (10), ESA response index (7), ferritin (12), hepcidin (3), and CRP (2); including polyunsaturated (PU)-ceramides, lysophosphatidylcholine, oxidized phosphoglycerolipid, Cho-esters and a statin.
Conclusion
In this study poor HD patient-ESA dose was associated with low LDL Cho levels suggesting ESA hypo-response is associated with LDL lipid composition including lipids associated cytotoxicity, proatherogenic pathways and a statin. Future/on-going work addresses anti-hyperlipidemic agents and ESA response.
Funding
- NIDDK Support