title: Comparative effects of cerivastatin and fenofibrate on the atherogenic lipoprotein phenotype in proteinuric renal disease.
abstract: Patients with nephrotic-range proteinuria have impaired clearance of triglyceride-rich lipoproteins. This results in the atherogenic lipoprotein phenotype (mild hypertriglyceridemia, low high-density lipoproteins [HDL], and excess small, dense low-density lipoproteins [LDLIII]). Excess remnant lipoproteins (RLP) are linked to hypertriglyceridemia and may contribute to the atherogenicity of nephrotic dyslipidemia. A randomized crossover study compared the effects of a statin (cerivastatin) and a fibrate (fenofibrate) on LDLIII and RLP in 12 patients with nephrotic-range proteinuria. Cerivastatin reduced cholesterol (21%, P: < 0.01), triglyceride (14%, P: < 0.05), LDL cholesterol (LDL-C; 23%, P: < 0.01), total LDL (18%, P: < 0.01), and LDLIII concentration (27% P: < 0.01). %LDLIII, RLP-C, and RLP triglyceride (RLP-TG) were unchanged. Plasma LDLIII reduction with cerivastatin treatment correlated with LDL-C reduction (r(2) = 34%, P: < 0.05). Fenofibrate lowered cholesterol (19%), triglyceride (41%), very low-density lipoprotein cholesterol (52%), LDLIII concentration (49%), RLP-C (35%), and RLP-TG (44%; all P: < 0.01). Fenofibrate also reduced %LDLIII from 60 to 33% (P: < 0.01). HDL-C (19%, P: < 0.01) increased with fenofibrate treatment; LDL-C and total LDL were unchanged. The reduction in LDLIII concentration and RLP-C with fenofibrate treatment correlated with plasma triglyceride reduction (LDLIII r(2) = 67%, P: < 0.001; RLP cholesterol r(2) = 58%, P: < 0.005). Serum creatinine increased with fenofibrate treatment (14%, P: < 0.01); however, creatinine clearance was unchanged. LDLIII concentration was 187 +/- 85 mg/dl after cerivastatin treatment and 133 +/- 95 mg/dl after fenofibrate treatment. Cerivastatin and fenofibrate reduce LDLIII concentration in nephrotic-range proteinuria. However, atherogenic concentrations of LDLIII remain prevalent after either treatment. Fenofibrate but not cerivastatin reduces remnant lipoproteins. The two treatments seem to reduce LDLIII by different mechanisms, suggesting a potential role for combination therapy to optimize lowering of LDLIII and RLP.
authors.affiliation: Renal Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom.|Department of Pathological Biochemistry, Glasgow Royal Infirmary, Glasgow, United Kingdom.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Deighan
authors.affiliation: Department of Pathological Biochemistry, Glasgow Royal Infirmary, Glasgow, United Kingdom.
authors.forename: Muriel J
authors.initials: MJ
authors.lastname: Caslake
authors.affiliation: Department of Pathological Biochemistry, Glasgow Royal Infirmary, Glasgow, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: McConnell
authors.affiliation: Renal Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Boulton-Jones
authors.affiliation: Department of Pathological Biochemistry, Glasgow Royal Infirmary, Glasgow, United Kingdom.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Packard
mesh_terms: D001161:Arteriosclerosis / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D015243:Cholesterol, VLDL / Q000097:blood; D018592:Cross-Over Studies; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010641:Phenotype; D011507:Proteinuria / Q000097:blood / Q000188:drug therapy*; D011725:Pyridines / Q000627:therapeutic use*
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D011725:Pyridines; C086276:cerivastatin; D011345:Fenofibrate