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Kidney Int. 2004 Mar;65(3):1064-75.

A broad-based metabolic approach to study VLDL apoB100 metabolism in patients with ESRD and patients treated with peritoneal dialysis.

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1
Department of Vascular Medicine and Metabolism, University Medical Center Utrecht, Utrecht, The Netherlands.

Abstract

BACKGROUND:

Dyslipidemia is often observed in patients with end-stage renal disease (ESRD) and is associated with cardiovascular diseases. Peritoneal dialysis treatment may further deteriorate the lipoprotein abnormalities, suggesting that peritoneal dialysis alters lipid metabolism.

METHODS:

To study the mechanisms involved in these abnormalities in peritoneal dialysis, we measured insulin sensitivity, free fatty acids release, de novo lipogenesis (DNL), very low-density lipoprotein (VLDL) apoB100 kinetics and cholesterol synthesis in vivo in ESRD (N= 6), peritoneal dialysis patients (N= 5), and controls (N= 7) using stable isotopes.

RESULTS:

Insulin sensitivity, as assessed by an euglycemic hyperinsulinemic clamp, tended to be lower in ESRD and peritoneal dialysis compared to controls [P= 0.08 by analysis of variance (ANOVA)]. Free fatty acid release during the euglycemic hyperinsulinemic clamp tended to be higher in ESRD and peritoneal dialysis compared to controls (P= 0.08 by ANOVA), while DNL and fractional cholesterol synthesis were normal. VLDL-1 apoB100 (P < 0.05) and VLDL-2 apoB100 pool sizes (P < 0.05) were significantly higher in peritoneal dialysis patients compared to controls. The increased VLDL-1 apoB100 pool size was explained by increased VLDL-1 apoB100 synthesis (P < 0.05) in combination with reduced VLDL-1 apoB100 catabolism (P < 0.01), while the increased VLDL-2 apoB100 pool was explained by reduced catabolism (P < 0.01).

CONCLUSION:

Both VLDL-1 apoB100 and VLDL-2 apoB100 pool sizes are increased in peritoneal dialysis patients, due to disturbances both in synthesis and catabolism. VLDL-1 apoB100 production is, at least partially, explained by increased free fatty acid availability secondary to peripheral insulin resistance, thus identifying insulin resistance as potential therapeutic target in peritoneal dialysis patients.

[Indexed for MEDLINE]
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