Effect of Simvastatin on Qualitative and Quantitative Changes of Lipoprotein Metabolism in CAPD Patients

Abstract

The efficacy of simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, was investigated in 12 patients treated with continuous ambulatory peritoneal dialysis (CAPD), displaying hypercholesterolemia and moderate hypertriglyceridemia. After a 4-week placebo period, simvastatin was administered in increasing doses over a period of 3 months (1^st month 10 mg; 2^nd month 20 mg and 3rd month 40 mg day^-1). Simvastatin reduced total serum cholesterol (300.0 + 15.5 vs. 193.0 ± 8.0; -35%), LDL cholesterol (203.8 ± 13.0 vs. 104.7 ± 6.0; -48.0%) as well as apolipoprotein B (132.3 ± 6.6 vs. 77.8 ± 2.7 mg/dl; -40%). Furthermore, the ratio of LDL apo B/LDL cholesterol increased significantly (0.55 ± 0.016 vs. 0.64 ± 0.027). Another remarkable effect was the reduction of cholesterol concentration in VLDL (47.8 ± 5.6 vs. 30.4 ± 5.2; -35%). Therefore, the ratio of triglycerides/cholesterol in VLDL increased (3.57 ± 0.3 vs. 4.28 ± 0.29), indicating VLDL formation poor in cholesterol and rich in triglycerides. However, HDL cholesterol increased significantly from 48.6 ± 4.4 to 57.9 ± 5.3 mg/dl (23%). Lipoprotein(a) levels were increased as compared to controls (420 ± 73 vs. 145 ± 26 U/l), but were not influenced significantly by simvastatin treatment (539 ± 99 U/l, 3rd month). No evidence for notable clinical side effects and laboratory abnormalities were reported. Measurement of simvastatin plasma levels 12 h after drug administration (single dose 40 mg) showed no detectable plasma values. At present, it appears that CAPD patients with high serum cholesterol are good candidates for the treatment with HMG-CoA reductase inhibitors.

The Effect of CAPD on the Lipid Profile of Pediatric Patients

“…Due to the causal relationship of atherosclerotic and thrombotic events and cardiovascular morbidity in adult CAPD patients (7), hyperlipidemia requires treatment with lipid lowering agents. The results of such treatments have been shown to be satisfactory (17,18). In pediatric CAPD patients, in spite of the establishment of dyslipidemia in the available reports (12-15), the risk of late development of cardiovascular disease and the criteria of treatment decision with lipid lowering drugs has yet to be defined.…”