Abstract: FR-PO476

Impaired Delivery of Cholesterol to Hepatocytes by Serum from CKD Patients: Implications for the Associated CVD Risk

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 303 CKD: Epidemiology, Outcomes - Cardiovascular

Authors

  • Carl, Daniel E., Virginia Commonwealth Univeristy, Richmond, Virginia, United States
  • Gipson, Graham Thomas, Virginia Commonwealth University, Richmond, Virginia, United States
  • Ghosh, Shobha, VCU, Richmond, Virginia, United States
  • Carbone, Salvatore, Virginia Commonwealth University, Richmond, Virginia, United States
  • Dixon, Dave L, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, United States
  • Jovin, Ion S, McGuire VAMC/VCU, Richmond, Virginia, United States
Background

Mortality in CKD patients is largely due to the development of CVD but the underlying mechanisms have not been elucidated. The flux of cholesterol through the body and final elimination by the liver rather than the plasma lipid profiles is now considered as a major contributor to development of CVD. Ability of the serum components to remove cholesterol from macrophage foam cells and deliver it to the liver for final elimination are the two critical steps in regulating cholesterol flux. Herein, we evaluated the ability of serum from CKD patients to facilitate these two processes.

Methods

Thirty-two consecutive patients with CKD (Stage 3, N=15 and Stage 4+5, N= 17) and 15 healthy subjects were enrolled in the study. Cholesterol efflux capacity (CEC) of the patient serum to remove cholesterol from human THP1 macrophage foam cells and the ability to deliver this effluxed cholesterol to primary hepatocytes was determined and compared between groups using the Mann-Whitney Test . Correlations between kidney function parameters, CEC and uptake by hepatocytes were performed using the Spearman’s nonparametric rank test.

Results

CEC was significantly higher with serum from patients with CKD (Stages 3 and 4+5, P<0.001) compared to that from healthy subjects (Panel A). However, the ability of this effluxed FC to be delivered to hepatocytes was significantly lower in patients with CKD (Panel B, Stages 3 and 4+5, P<0.001). eGFR was inversely associated with CEC (Panel C) and positively associated with hepatocyte uptake (Panel D).

Conclusion

These data indicate that impaired delivery of cholesterol to the liver for final elimination from the body likely underlies the development of CVD in CKD patients. Studies are in progress to determine if this decrease in hepatocyte uptake in CKD is related to modifications of cholesterol carrying serum components (e.g., HDL or albumin) by reduced kidney function.