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Defect in cholesterol transport in patients receiving maintenance hemodialysis
Insights
Patients undergoing hemodialysis show impaired cholesterol transport, specifically a reduced rate of cholesterol transfer between lipoproteins. This defect, observed in vitro, may contribute to cardiovascular risks and requires further investigation in living patients.
Area of Science:
- Lipid Metabolism
- Renal Disease Pathophysiology
- Cardiovascular Research
Background:
- Patients with uremia undergoing long-term hemodialysis often exhibit dyslipidemia.
- Altered cholesterol metabolism may contribute to the increased cardiovascular risk in these patients.
Purpose of the Study:
- To investigate potential defects in cholesterol transport in patients with uremia undergoing hemodialysis.
- To compare the rate of cholesterol transfer (RCT) between lipoproteins in uremic patients and healthy controls.
Main Methods:
- Collected serum from uremic patients on hemodialysis and healthy controls.
- Measured the rate of cholesterol transfer (RCT) from high-density lipoprotein (HDL) to very low-density (VLDL) and low-density lipoproteins (LDL) in vitro.
- Utilized ultracentrifugation to separate serum fractions for recombination and crossover studies.
Main Results:
- Uremic patients exhibited significantly lower RCT compared to controls (P < 0.001).
- Six patients completely lacked cholesterol transfer ability, unlike controls.
- The defect was localized to the HDL-containing fraction (d > 1.063 gm/ml), which was qualitatively inferior for cholesterol donation.
- In some cases, the VLDL/LDL fraction (d < 1.063 gm/ml) also showed impaired cholesteryl ester acceptance.
Conclusions:
- In vitro studies indicate a defect in cholesterol transport in patients undergoing hemodialysis.
- This impaired cholesterol transport may be an intrinsic abnormality in uremia.
- Further in vivo studies are needed to determine if this defect contributes to accelerated atherosclerosis.
Abstract:
A defect in cholesterol transport was detected in patients with uremia who were receiving long-term hemodialysis when the rate of cholesterol transfer (RCT) from high-density lipoprotein (HDL) to very low-density (VLDL) and low-density lipoproteins (LDL) was compared with that in controls. The RCT (mean +/- SD) in 29 men with uremia (1.85 +/- 1.29 mg/hr/100 ml) and 11 women with uremia (1.84 +/- 1.00 mg/hr/100 ml) was significantly lower (P less than 0.001) than values in 55 healthy men (4.50 +/- 2.61 mg/hr/100 ml) and 23 healthy women (3.72 +/- 1.92 mg/hr/100 ml), respectively. Six patients, but none of the controls, totally lacked the ability for cholesterol transfer. The decreased RCT of the patients could not be completely accounted for by their decreased HDL cholesterol levels, because patients matched with controls for HDL cholesterol within 1 mg/100 ml also had lower RCT (P less than 0.0025). Recombination and crossover of serum fractions of patients and controls separated by ultracentrifugation revealed that the defect in cholesterol transfer of the patients was in the d greater than 1.063 gm/ml fraction (containing HDL and other serum proteins), which not only contained less HDL cholesterol, but was also qualitatively inferior as donor for cholesterol transfer. In one of four patients studied, the d less than 1.063 gm/ml fraction (VLDL and LDL) also had deficient ability to accept cholesteryl esters in the transfer. These in vitro data indicate a defect in cholesterol transport in the patients who are undergoing hemodialysis. Whether this defect exists in vivo and creates the risk of accelerated atherosclerosis warrants further study.