Effect of fenofibrate on kidney function: a 6-week randomized crossover trial in healthy people.

BACKGROUND: Fenofibrate was associated with increases in serum creatinine concentrations. The effect of short-term fenofibrate treatment on kidney function was investigated in subjects with normal kidney function. STUDY
DESIGN: Double-blind, crossover, placebo-controlled. SETTING AND PARTICIPANTS: 24 middle-aged subjects with normal kidney function (estimated creatinine clearance > or = 80 mL/min). INTERVENTION: Subjects were treated with fenofibrate (160-mg/d tablet) and placebo in two 6-week periods separated by a washout. OUTCOMES AND MEASUREMENTS: The primary outcome measure was glomerular filtration rate measured by means of inulin clearance, with a test of noninferiority to rule out a change in the 95% confidence interval (CI) greater than 20%. Secondary outcomes included effective renal plasma flow measured by means of para-aminohippurate (PAH) clearance, creatinine clearance, creatinine secretion (ratio of creatinine to inulin clearance), serum cystatin C and uric acid, and urinary excretion of creatinine. Glomerular and tubular damage was evaluated by using albumin and retinol-binding protein levels and N-acetyl-beta-d-glucosaminidase activity.
RESULTS: Inulin clearance was unchanged after fenofibrate (change [Delta] between treatments on 6-week values, 0.8 mL/min; 95% CI, -10.5 to 12.2; P = 0.9), but PAH clearance decreased (Delta, -33; 95% CI, -66 to -1; P = 0.05). Changes in inulin and PAH clearances were not greater than 20%. Plasma creatinine level increased (Delta, 0.11 mg/dL; 95% CI, 0.05 to 0.18; P < 0.05), and creatinine clearance decreased (Delta, -9.5 mL/min; 95% CI, -14.4 to -4.7; P < 0.001). Creatinine secretion and urinary creatinine excretion were unchanged (Delta, -0.05; 95% CI, -0.11 to 0.02; P = 0.2; Delta, 0.37 g/24 h; 95% CI, -0.13 to 0.88; P = 0.1, respectively). Plasma cystatin C level increased (Delta, 0.18 mg/L; 95% CI, 0.03 to 0.34; P = 0.02) and serum uric acid level decreased (Delta, -0.7 mg/dL; 95% CI, -1.2 to -0.3; P = 0.1). Urinary albumin and retinol-binding protein levels were unchanged, but urinary N-acetyl-beta-d-glucosaminidase activity increased (Delta, 20.0 mumol/h/mmol creatinine; 95% CI, 9.3 to 30.7; P = 0.001). LIMITATIONS: Short treatment duration and inclusion of healthy subjects precludes conclusions about effects of longer term use in patients with kidney disease. Small changes in glomerular filtration rate may be difficult to detect by using clearance methods. Interference with the creatinine assay cannot be excluded.
CONCLUSION: Short-term fenofibrate treatment did not alter glomerular filtration rate by more than 20% in subjects with normal kidney function, but a smaller decrease cannot be ruled out. Increased serum creatinine levels may be caused by decreased creatinine clearance. The explanation for decreased creatinine clearance and increased serum creatinine levels in this study is not clear.

RCT Entities:   Population Interventions Outcomes