Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study
Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study
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DOI：
10.1007/s00125-010-1951-1
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发表时间：
2011-02-01
期刊：
影响因子：
8.2
通讯作者：
Keech, A. C.
中科院分区：
文献类型：
--
作者：
Davis, T. M. E.;Ting, R.;Keech, A. C.
在非诺贝特干预和降低糖尿病事件 (FIELD) 和控制糖尿病心血管风险行动 (ACCORD) 研究中，非诺贝特导致血浆肌酐急性、持续升高。我们在现场清除子研究中全面评估了非诺贝特的肾脏影响。在 6 周非诺贝特磨合后，年龄 50 至 75 岁的 2 型糖尿病患者 (n = 9,795) 被随机分配到非诺贝特 (n = 4,895) 或安慰剂 (n = 4,900) 治疗 5 年。白蛋白尿（在基线、第 2 年和结束时测量的尿白蛋白/肌酐比率）和估计 GFR（根据肾病饮食调整研究每月四到六个月测量）是预先指定的终点。治疗结束后 8 周重新测量血浆肌酐（洗脱子研究，n = 661）。通过意向治疗进行分析。在非诺贝特导入期间，血浆肌酐增加了 10.0 μmol/l (p < 0.001)，但在安慰剂分配后迅速逆转。非诺贝特组仍高于安慰剂组，但慢性上升较慢（每年 1.62 vs 1.89 mu mol/l，p = 0.01），估计 GFR 损失较少（每年 1.19 vs 2.03 ml min(-1) 1.73 m(-2)，p < 0.001）。清除后，非诺贝特组的估计 GFR 从基线下降幅度较小 (1.9 ml min(-1) 1.73 m(-2)，p = 0.065)，比安慰剂组 (6.9 ml min(-1) 1.73 m(-2)，p < 0.001) 下降较少，保留 5.0 ml min(-1) 1.73 m(-2) (95% CI 2.3-7.7，p < 0.001）。单独观察基线高三酰基甘油血症（n = 169 对比 491 没有）或与低 HDL 胆固醇（n = 140 对比 520 没有）联合使用非诺贝特可以更好地保留估计的 GFR，并且在主动磨合期（随机化前）期间三酰甘油减少千分之一日元 0.48 mmol/l（n = 356 对比 303 没有）。与安慰剂组相比，非诺贝特可降低尿白蛋白浓度，从而使白蛋白/肌酐比降低 24% vs 11%（p < 0.001；平均差 14% [95% CI 9-18]；p < 0.001），进展减少 14%，白蛋白尿消退增加 18%（p < 0.001）。终末期肾脏事件频率相似（n = 21 vs 26，p = 0.48）。尽管最初可逆地增加血浆肌酐，但非诺贝特在 5 年内减少了蛋白尿并减缓了估计 GFR 损失。非诺贝特可能会延迟 2 型糖尿病患者的蛋白尿和 GFR 损伤。值得进行验证性研究。ISRCTN64783481该研究由 Laboratoires Fournier SA（法国第戎；现为雅培制药公司的一部分）和澳大利亚国家健康与医学研究委员会资助。
Fenofibrate caused an acute, sustained plasma creatinine increase in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies. We assessed fenofibrate's renal effects overall and in a FIELD washout sub-study.Type 2 diabetic patients (n = 9,795) aged 50 to 75 years were randomly assigned to fenofibrate (n = 4,895) or placebo (n = 4,900) for 5 years, after 6 weeks fenofibrate run-in. Albuminuria (urinary albumin/creatinine ratio measured at baseline, year 2 and close-out) and estimated GFR, measured four to six monthly according to the Modification of Diet in Renal Disease Study, were pre-specified endpoints. Plasma creatinine was re-measured 8 weeks after treatment cessation at close-out (washout sub-study, n = 661). Analysis was by intention-to-treat.During fenofibrate run-in, plasma creatinine increased by 10.0 mu mol/l (p < 0.001), but quickly reversed on placebo assignment. It remained higher on fenofibrate than on placebo, but the chronic rise was slower (1.62 vs 1.89 mu mol/l annually, p = 0.01), with less estimated GFR loss (1.19 vs 2.03 ml min(-1) 1.73 m(-2) annually, p < 0.001). After washout, estimated GFR had fallen less from baseline on fenofibrate (1.9 ml min(-1) 1.73 m(-2), p = 0.065) than on placebo (6.9 ml min(-1) 1.73 m(-2), p < 0.001), sparing 5.0 ml min(-1) 1.73 m(-2) (95% CI 2.3-7.7, p < 0.001). Greater preservation of estimated GFR with fenofibrate was observed with baseline hypertriacylglycerolaemia (n = 169 vs 491 without) alone, or combined with low HDL-cholesterol (n = 140 vs 520 without) and reductions of a parts per thousand yen0.48 mmol/l in triacylglycerol over the active run-in period (pre-randomisation) (n = 356 vs 303 without). Fenofibrate reduced urine albumin concentrations and hence albumin/creatinine ratio by 24% vs 11% (p < 0.001; mean difference 14% [95% CI 9-18]; p < 0.001), with 14% less progression and 18% more albuminuria regression (p < 0.001) than in participants on placebo. End-stage renal event frequency was similar (n = 21 vs 26, p = 0.48).Fenofibrate reduced albuminuria and slowed estimated GFR loss over 5 years, despite initially and reversibly increasing plasma creatinine. Fenofibrate may delay albuminuria and GFR impairment in type 2 diabetes patients. Confirmatory studies are merited.ISRCTN64783481The study was funded by grants from Laboratoires Fournier SA (Dijon, France; now part of Abbott Pharmaceuticals) and the National Health and Medical Research Council, Australia.