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Published on: May 22, 2017
Alteration of HDL Protein Composition with Hemodialysis Initiation
Ke Wang1,2, Leila R Zelnick1,2, Andrew N Hoofnagle1,3,2
1Departments of Medicine and.
Insights
Hemodialysis initiation alters HDL proteins, increasing inflammatory markers and potentially impairing cholesterol efflux. This suggests hemodialysis may worsen cardiovascular risk in CKD patients.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Proteomics
Background:
- Chronic kidney disease (CKD) is linked to altered high-density lipoprotein (HDL) function.
- HDL from hemodialysis patients shows reduced cholesterol efflux and increased inflammatory proteins.
- The hemodialysis procedure itself may contribute to these HDL changes.
Purpose of the Study:
- To compare HDL-associated proteins in patients initiating hemodialysis versus those with advanced CKD.
- To investigate the impact of hemodialysis initiation on HDL protein profiles and cholesterol efflux capacity.
Main Methods:
- Targeted mass spectrometry quantified 38 HDL-associated proteins in 143 new hemodialysis patients and 110 advanced CKD patients.
- Linear regression with false discovery rate control (q ≤10%) analyzed protein abundances.
- Cholesterol efflux capacity was assessed in a subset of participants.
Main Results:
- Eight HDL proteins (serum amyloid A1, A2, A4; hemoglobin-β; haptoglobin-related protein; cholesterylester transfer protein; phospholipid transfer protein; apo E) were significantly higher after hemodialysis initiation.
- A trend towards lower cholesterol efflux capacity was observed in new hemodialysis patients, but did not reach statistical significance.
- These findings differ from protein alterations seen in non-dialysis CKD.
Conclusions:
- Hemodialysis initiation is associated with increased HDL concentrations of proteins involved in inflammation and lipid metabolism.
- These protein changes may further compromise HDL function and cholesterol efflux capacity.
- Further research is needed to determine the clinical significance of these HDL protein alterations for cardiovascular risk in CKD patients.
Background And Objectives:
HDL particles obtained from patients on chronic hemodialysis exhibit lower cholesterol efflux capacity and are enriched in inflammatory proteins compared with those in healthy individuals. Observed alterations in HDL proteins could be due to effects of CKD, but also may be influenced by the hemodialysis procedure, which stimulates proinflammatory and prothrombotic pathways.
Design, Setting, Participants, & Measurements:
We compared HDL-associated proteins in 143 participants who initiated hemodialysis within the previous year with those of 110 participants with advanced CKD from the Hemodialysis Fistula Maturation Study. We quantified concentrations of 38 HDL-associated proteins relative to total HDL protein using targeted mass spectrometry assays that included a stable isotope-labeled internal standard. We used linear regression to compare the relative abundances of HDL-associated proteins after adjustment and required a false discovery rate q value ≤10% to control for multiple testing. We further assessed the association between hemodialysis initiation and cholesterol efflux capacity in a subset of 80 participants.
Results:
After adjustment for demographics, comorbidities, and other clinical characteristics, eight HDL-associated proteins met the prespecified false discovery threshold for association. Recent hemodialysis initiation was associated with higher HDL-associated concentrations of serum amyloid A1, A2, and A4; hemoglobin-β; haptoglobin-related protein; cholesterylester transfer protein; phospholipid transfer protein; and apo E. The trend for participants recently initiating hemodialysis for lower cholesterol efflux capacity compared with individuals with advanced CKD did not reach statistical significance.
Conclusions:
Compared with advanced CKD, hemodialysis initiation within the previous year is associated with higher concentrations of eight HDL proteins related to inflammation and lipid metabolism. Identified associations differ from those recently observed for nondialysis-requiring CKD. Hemodialysis initiation may further impair cholesterol efflux capacity. Further work is needed to clarify the clinical significance of the identified proteins with respect to cardiovascular risk.
Podcast:
This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_07_25_CJASNPodcast_18_8_W.mp3.
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