Effect of treatment with simvastatin on serum cholestryl ester transfer in patients on dialysis (original) (raw)

1997, Nephrology Dialysis Transplantation

Introduction Background. Plasma cholesteryl ester transfer activity is increased in patients with chronic renal failure on Transfer of cholesteryl esters from high-density lipodialysis who have elevated levels of apolipoprotein proteins (HDL) to other lipoproteins is catalysed by B (apoB)-containing lipoproteins. Simvastatin, a 3-hycholesteryl ester transfer protein in plasma and is part droxy-3-methylglutaryl coenzyme A (HMG CoA) of a pathway which returns cholesterol from peripheral reductase inhibitor, reduces levels of these lipoproteins tissues to the liver where the sterol can be excreted but the effect of treatment on cholesteryl ester transfer (reverse cholesterol transport). In this pathway, tissue activity in patients on dialysis remains to be cholesterol is bound by HDL, esterified by lecithin:chodetermined. lesterol acyltransferase (LCAT) activity and a substan-Methods. We measured serum newly synthesized choletial portion of the newly synthesized cholesteryl esters steryl ester transfer (NCET) activity, lecithin:cholesare transferred to apolipoprotein B(apoB)-containing terol acyltransferase (LCAT) activity and serum lipid, lipoproteins [1 ] which are removed from the circulation lipoprotein and apolipoprotein concentrations before by hepatic receptors. If this clearance is inefficient then and immediately after 6 months treatment with simvasplasma levels of apoB-containing lipoproteins increase tatin (10 mg daily, n=24) or placebo (n=29) in 53 and transfer of cholesteryl esters to these acceptors is patients with chronic renal failure receiving haemodiaaccelerated [2]. Thus treatment with drugs such as lysis or continuous ambulatory peritoneal dialysis 3-hydroxy-3-methylglutaryl Coenzyme A (HMG CoA) (CAPD). reductase inhibitors that up-regulate hepatic apoB,E Results. Simvastatin therapy significantly reduced receptor numbers and reduce plasma levels of apoBserum cholesterol, LDL cholesterol, apoB concentralipoproteins should also reduce plasma cholesteryl ester tions, and both NCET (P=0.001) and LCAT (P= transfer activity. 0.012) rates. The decrease in NCET activity was correl-The effect of HMG CoA reductase inhibitors on ated significantly with the corresponding decrease in plasma cholesteryl ester transfer activity has been apoB concentration (r=0.715, P<0.001) and LCAT documented in familial hypercholesterolaemia [2,3], activity (r=0.715, P<0.001) during simvastatin non-insulin-dependent diabetes mellitus [4 ] and in northerapy and was no longer significant when apoB molipidaemic subjects [5 ]. A decrease in plasma cholesconcentration (P=0.14) or LCAT activity (P=0.07) teryl ester mass transfer activity was observed in most were controlled. but not all [3 ] studies. In patients with familial hyperch-Conclusions. These data show that simvastatin therapy olesterolaemia the decrease in plasma cholesteryl ester reduces serum NCET rates, and suggest that this may transfer activity has been linked to the concomitant be linked to the concomitant decrease in levels of decrease in LDL particle acceptor concentration during apoB-containing lipoproteins which are acceptors of simvastatin therapy [2]. The effect of simvastatin transferred cholesteryl esters, and to the decrease in therapy on plasma cholesteryl ester transfer activity in serum LCAT rates in patients with chronic renal failure patients with chronic renal failure has not been studied. with treatment. In patients with chronic renal failure, plasma levels Key words: cholesteryl ester transfer; dialysis; of cholesteryl ester acceptor lipoproteins including simvastatin VLDL, intermediate density lipoprotein (IDL) and other remnants of triglyceride-rich lipoprotein metabolism, are frequently elevated and HDL levels are Correspondence and offprint requests to: Robert J. Walker, low [6-8]. We have previously documented increased