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. 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  &lt; 0.01), triglyceride (14%,  P  &lt; 0.05), LDL  cholesterol (LDL-C; 23%,  P  &lt; 0.01), total LDL (18%,  P   &lt; 0.01), and LDLIII concentration (27%  P  &lt; 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  &lt; 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  &lt; 0.01).  Fenofibrate also reduced %LDLIII from 60 to 33% ( P  &lt; 0.01). HDL-C  (19%,  P  &lt; 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  &lt; 0.001; RLP cholesterol r 2  =  58%,  P  &lt; 0.005). Serum creatinine increased with fenofibrate  treatment (14%,  P  &lt; 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.

Comparative Effects of Cerivastatin and Fenofibrate on the Atherogenic Lipoprotein Phenotype in Proteinuric Renal Disease