Ansquer Jean-Claude, Dalton R Neil, Caussé Elisabeth, Crimet Dominique, Le Malicot Karine, Foucher Christelle
Laboratoires Fournier, Daix, France.
Am J Kidney Dis. 2008 Jun;51(6):904-13. doi: 10.1053/j.ajkd.2008.01.014. Epub 2008 Apr 2.
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.
Double-blind, crossover, placebo-controlled.
24 middle-aged subjects with normal kidney function (estimated creatinine clearance > or = 80 mL/min).
Subjects were treated with fenofibrate (160-mg/d tablet) and placebo in two 6-week periods separated by a washout.
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.
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).
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.
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.
非诺贝特与血清肌酐浓度升高有关。本研究在肾功能正常的受试者中调查了短期非诺贝特治疗对肾功能的影响。
双盲、交叉、安慰剂对照试验。
24名肾功能正常的中年受试者（估计肌酐清除率≥80 mL/分钟）。
受试者在两个6周疗程中分别接受非诺贝特（160毫克/天片剂）和安慰剂治疗，两个疗程之间设有洗脱期。
主要观察指标是通过菊粉清除率测定的肾小球滤过率，采用非劣效性检验以排除95%置信区间（CI）变化大于20%的情况。次要观察指标包括通过对氨基马尿酸（PAH）清除率测定的有效肾血浆流量、肌酐清除率、肌酐分泌（肌酐与菊粉清除率之比）、血清胱抑素C和尿酸，以及尿肌酐排泄。通过白蛋白和视黄醇结合蛋白水平以及N - 乙酰 - β - D - 氨基葡萄糖苷酶活性评估肾小球和肾小管损伤。
非诺贝特治疗后菊粉清除率无变化（两个疗程6周时的值之间的变化[Δ]为0.8 mL/分钟；95% CI为 - 10.5至12.2；P = 0.9），但PAH清除率下降（Δ为 - 33；95% CI为 - 66至 - 1；P = 0.05）。菊粉和PAH清除率的变化不超过20%。血浆肌酐水平升高（Δ为0.11毫克/分升；95% CI为0.05至0.18；P < 0.05），肌酐清除率下降（Δ为 - 9.5 mL/分钟；95% CI为 - 14.4至 - 4.7；P < 0.001）。肌酐分泌和尿肌酐排泄无变化（Δ为 - 0.05；95% CI为 - 0.11至0.02；P = 0.2；Δ为0.37克/24小时；95% CI为 - 0.13至0.88；P = 0.1）。血浆胱抑素C水平升高（Δ为0.18毫克/升；95% CI为0.03至0.34；P = 0.02），血清尿酸水平下降（Δ为 - 0.7毫克/分升；95% CI为 - 1.2至 - 0.3；P = 0.1）。尿白蛋白和视黄醇结合蛋白水平无变化，但尿N - 乙酰 - β - D - 氨基葡萄糖苷酶活性升高（Δ为20.0微摩尔/小时/毫摩尔肌酐；95% CI为9.3至30.7；P = 0.001）。
治疗持续时间短且纳入健康受试者，无法得出关于肾病患者长期使用效果的结论。使用清除率方法可能难以检测到肾小球滤过率的微小变化。不能排除对肌酐测定的干扰。
在肾功能正常的受试者中，短期非诺贝特治疗使肾小球滤过率的改变不超过20%，但不能排除较小程度的下降。血清肌酐水平升高可能是由于肌酐清除率降低所致。本研究中肌酐清除率降低和血清肌酐水平升高的原因尚不清楚。
