Tsutomu Kazumi1, Tsutomu Hirano2, Gen Yoshino3. 1. Department of Food Sciences and Nutrition, School of Human Environmental Sciences, Mukogawa Women's University, Hyogo, Japan. 2. First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan, and. 3. Department of Laboratory Medicine, Toho University School of Medicine, Tokyo, Japan.
Abstract
BACKGROUND: A slight increase in albuminuria (urinary albumin excretion [UAE] ≥30 mg/d) is associated with hypertension, type 2 diabetes mellitus, dyslipidemia (high triglyceride [TG] and low high-density lipoprotein cholesterol [HDL-C] concentrations), and hyperuricemia. Although antihypertensive and antidiabetic therapies have been reported to reduce UAE, an association between improvement in dyslipidemia and/or hyperuricemia and a reduction in UAE has not been reported. OBJECTIVE: The aim of this study was to investigate the efficacy and tolerability of fenofibrate on albuminuria in patients with hypertriglyceridemia and/or hyperuricemia. METHODS:Patients with hypertriglyceridemia and/or hyperuricemia were recruited from general clinics and lipid clinics in Japan; they received fenofibrate (300 mg once daily) in this randomized, double-blind, placebo-controlled, crossover study. Patients in group A received fenofibrate for 8 weeks followed by placebo for an additional 8 weeks, whereas those in group B received placebo for 8 weeks followed by fenofibrate for 8 additional weeks. UAE was measured at baseline and at the end of each 8-week period. Blood tests were performed at baseline and every 4 weeks until study end. Each physician who participated in the study was to record adverse events at each study visit. RESULTS: A total of 43 patients entered this study (38 men, 5 women; mean [SE] age, 57.1 [1.4] years; mean [SE] body mass index, 24.3 [0.4] kg/m(2)). Twenty-one patients (18 men, 3 women) were randomly assigned to group A and 22 (20 men, 2 women) to group B. In group A, serum TG (P<0.001) and apolipoprotein (apo) C2, C3, and E (all P<0.01) concentrations decreased significantly with fenofibrate, and HDL-C and apo A1 and A2 increased significantly (all P<0.001). All of these parameters returned to near-baseline levels after placebo administration. In group B, serum TG, HDL-C, or apo A1, A2, B, C2, C3, and E concentrations did not change significantly with placebo, but TG (P<0.01), apo C3 (P<0.05), and apo E (P<0.05) were significantly decreased with fenofibrate. In addition, HDL-C (P<0.05), apo A1 (P<0.001), and apo A2 (P<0.01) were significantly increased with fenofibrate. Serum concentrations of TG (group A, P<0.001; group B, P<0.001); apo C2 (group A, P<0.01), C3 (group A, P<0.01; group B, P<0.05), and E (group A, P<0.01; group B, P<0.05); and uric acid (group A, P<0.001; group B, P<0.01) were significantly decreased with fenofibrate compared with placebo. HDL-C and apo A1 and A2 were significantly increased with fenofibrate compared with placebo (all P<0.001 in both groups). Fenofibrate treatment was associated with significant reductions in UAE (group A, P<0.05; group B, P<0.01). Spearman rank correlation analysis showed that changes in UAE were associated with changes in apo C2 (ρ = 0.43; P = 0.02) and apo C3 (ρ = 0.49; P = 0.01) concentrations. Multiple regression analysis revealed that a decrease in apo C3 concentration was independently and significantly associated with reductions in albuminuria (ρ = 0.48; P = 0.01). At the end of the study, neither drug-related nor clinical adverse events were evident in any of the patients, except for an increase in serum creatinine concentration above the upper limit of normal (1.40 mg/dL) in 3 patients (14.3%) in group A and 1 patient (4.5%) in group B. CONCLUSIONS: In our study population of patients with hypertriglyceridemia and/or hyperuricemia, fenofibrate-induced ameliorations of impaired TG-rich lipoprotein metabolism were associated with reductions in albuminuria.
RCT Entities:
BACKGROUND: A slight increase in albuminuria (urinary albumin excretion [UAE] ≥30 mg/d) is associated with hypertension, type 2 diabetes mellitus, dyslipidemia (high triglyceride [TG] and low high-density lipoprotein cholesterol [HDL-C] concentrations), and hyperuricemia. Although antihypertensive and antidiabetic therapies have been reported to reduce UAE, an association between improvement in dyslipidemia and/or hyperuricemia and a reduction in UAE has not been reported. OBJECTIVE: The aim of this study was to investigate the efficacy and tolerability of fenofibrate on albuminuria in patients with hypertriglyceridemia and/or hyperuricemia. METHODS:Patients with hypertriglyceridemia and/or hyperuricemia were recruited from general clinics and lipid clinics in Japan; they received fenofibrate (300 mg once daily) in this randomized, double-blind, placebo-controlled, crossover study. Patients in group A received fenofibrate for 8 weeks followed by placebo for an additional 8 weeks, whereas those in group B received placebo for 8 weeks followed by fenofibrate for 8 additional weeks. UAE was measured at baseline and at the end of each 8-week period. Blood tests were performed at baseline and every 4 weeks until study end. Each physician who participated in the study was to record adverse events at each study visit. RESULTS: A total of 43 patients entered this study (38 men, 5 women; mean [SE] age, 57.1 [1.4] years; mean [SE] body mass index, 24.3 [0.4] kg/m(2)). Twenty-one patients (18 men, 3 women) were randomly assigned to group A and 22 (20 men, 2 women) to group B. In group A, serum TG (P<0.001) and apolipoprotein (apo) C2, C3, and E (all P<0.01) concentrations decreased significantly with fenofibrate, and HDL-C and apo A1 and A2 increased significantly (all P<0.001). All of these parameters returned to near-baseline levels after placebo administration. In group B, serum TG, HDL-C, or apo A1, A2, B, C2, C3, and E concentrations did not change significantly with placebo, but TG (P<0.01), apo C3 (P<0.05), and apo E (P<0.05) were significantly decreased with fenofibrate. In addition, HDL-C (P<0.05), apo A1 (P<0.001), and apo A2 (P<0.01) were significantly increased with fenofibrate. Serum concentrations of TG (group A, P<0.001; group B, P<0.001); apo C2 (group A, P<0.01), C3 (group A, P<0.01; group B, P<0.05), and E (group A, P<0.01; group B, P<0.05); and uric acid (group A, P<0.001; group B, P<0.01) were significantly decreased with fenofibrate compared with placebo. HDL-C and apo A1 and A2 were significantly increased with fenofibrate compared with placebo (all P<0.001 in both groups). Fenofibrate treatment was associated with significant reductions in UAE (group A, P<0.05; group B, P<0.01). Spearman rank correlation analysis showed that changes in UAE were associated with changes in apo C2 (ρ = 0.43; P = 0.02) and apo C3 (ρ = 0.49; P = 0.01) concentrations. Multiple regression analysis revealed that a decrease in apo C3 concentration was independently and significantly associated with reductions in albuminuria (ρ = 0.48; P = 0.01). At the end of the study, neither drug-related nor clinical adverse events were evident in any of the patients, except for an increase in serum creatinine concentration above the upper limit of normal (1.40 mg/dL) in 3 patients (14.3%) in group A and 1 patient (4.5%) in group B. CONCLUSIONS: In our study population of patients with hypertriglyceridemia and/or hyperuricemia, fenofibrate-induced ameliorations of impaired TG-rich lipoprotein metabolism were associated with reductions in albuminuria.
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