Related Experiment Video
Updated: Apr 4, 2026
Cholesterol Efflux Assay
Published on: March 6, 2012
HDL Cholesterol Efflux Predicts Graft Failure in Renal Transplant Recipients
Wijtske Annema1, Arne Dikkers2, Jan Freark de Boer2
1Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Top Institute Food and Nutrition, Wageningen, The Netherlands;
Insights
Cholesterol efflux capacity, a key function of high-density lipoprotein (HDL) particles, does not predict cardiovascular or all-cause mortality in kidney transplant recipients. However, it is a significant predictor of graft failure.
Area of Science:
- Cardiovascular Science
- Transplantation Immunology
- Lipid Metabolism
Background:
- High-density lipoprotein (HDL) particles are crucial for reverse cholesterol transport, a process vital in preventing cardiovascular disease.
- Cholesterol efflux capacity (CEC) quantifies HDL's ability to remove cholesterol from cells, particularly macrophage foam cells.
- The role of CEC in outcomes for renal transplant recipients, including mortality and graft survival, remains incompletely understood.
Purpose of the Study:
- To investigate the association between baseline HDL cholesterol efflux capacity and cardiovascular mortality, all-cause mortality, and graft failure in renal transplant recipients.
- To determine if CEC is an independent predictor of these adverse outcomes.
Main Methods:
- A prospective cohort study of 495 renal transplant recipients was conducted with a median follow-up of 7.0 years.
- Cholesterol efflux capacity was measured at baseline by incubating macrophage foam cells with apolipoprotein B-depleted plasma.
- Outcomes including cardiovascular mortality, all-cause mortality, and graft failure were assessed using Kaplan-Meier analysis and Cox regression.
Main Results:
- Baseline cholesterol efflux capacity was not significantly different between survivors and deceased patients for either cardiovascular or all-cause mortality.
- Recipients who experienced graft failure had significantly lower baseline efflux capacity compared to those with functioning grafts.
- Increasing tertiles of efflux capacity were associated with a reduced risk of graft failure but not mortality.
- Cholesterol efflux capacity independently predicted graft failure, even after adjusting for apolipoprotein A-I, HDL cholesterol, and creatinine clearance.
Conclusions:
- Cholesterol efflux capacity is not associated with cardiovascular or all-cause mortality in renal transplant recipients.
- Cholesterol efflux capacity is a robust, independent predictor of graft failure in this patient population.
- These findings highlight the importance of CEC beyond traditional HDL cholesterol levels for predicting transplant outcomes.
Abstract:
High-density lipoprotein (HDL) particles are involved in the protection against cardiovascular disease by promoting cholesterol efflux, in which accumulated cholesterol is removed from macrophage foam cells. We investigated whether HDL cholesterol efflux capacity is associated with cardiovascular mortality, all-cause mortality, and graft failure in a cohort of renal transplant recipients (n=495, median follow-up 7.0 years). Cholesterol efflux capacity at baseline was quantified using incubation of human macrophage foam cells with apolipoprotein B-depleted plasma. Baseline efflux capacity was not different in deceased patients and survivors (P=0.60 or P=0.50 for cardiovascular or all-cause mortality, respectively), whereas recipients developing graft failure had lower efflux capacity than those with functioning grafts (P<0.001). Kaplan-Meier analysis demonstrated a lower risk for graft failure (P=0.004) but not cardiovascular (P=0.30) or all-cause mortality (P=0.31) with increasing gender-stratified tertiles of efflux capacity. Cox regression analyses adjusted for age and gender showed that efflux capacity was not associated with cardiovascular mortality (hazard ratio [HR], 0.89; 95% confidence interval [95% CI], 0.67 to 1.19; P=0.43). Furthermore, the association between efflux capacity and all-cause mortality (HR, .79; 95% CI, 0.63 to 0.98; P=0.031) disappeared after further adjustment for potential confounders. However, efflux capacity at baseline significantly predicted graft failure (HR, 0.43; 95% CI, 0.29 to 0.64; P<0.001) independent of apolipoprotein A-I, HDL cholesterol, or creatinine clearance. In conclusion, this prospective study shows that cholesterol efflux capacity from macrophage foam cells is not associated with cardiovascular or all-cause mortality but is a strong predictor of graft failure independent of plasma HDL cholesterol levels in renal transplant recipients.
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