Frazier Rebecca, Mehta Rupal, Cai Xuan, Lee Jungwha, Napoli Sara, Craven Timothy, Tuazon Jennifer, Safdi Adam, Scialla Julia, Susztak Katalin, Isakova Tamara
Division of Nephrology and Hypertension, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Kidney Int Rep. 2018 Sep 18;4(1):94-102. doi: 10.1016/j.ekir.2018.09.006. eCollection 2019 Jan.
Abnormalities in lipid metabolism may contribute to the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes. Fenofibrate induces early and reversible reduction in estimated glomerular filtration rate (eGFR), but it may have protective effects on microvascular complications of diabetes. We hypothesized that randomization to fenofibrate versus placebo would be associated with beneficial long-term effects on kidney outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants.
We conducted a analysis in the ACCORD Lipid Trial to examine the association of randomization to fenofibrate versus placebo with change in eGFR and with time-to-development of microalbuminuria, macroalbuminuria, CKD, and kidney failure.
We analyzed 2636 participants in the fenofibrate arm and 2632 in the placebo arm. During a median follow-up of 4 years, treatment with fenofibrate was associated with lower rate of eGFR decline (-0.28 ml/min per 1.73 m per year in the fenofibrate group vs. -1.25 ml/min per 1.73 m per year in the placebo group, < 0.01) and with lower incidence of microalbuminuria (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.43-0.72, < 0.001) and macroalbuminuria (HR 0.72, 95% CI 0.57-0.91, < 0.001). There was no difference in incidence of CKD (HR 0.92, 95% CI 0.74-1.15, = 0.46) and/or kidney failure (HR 0.95, 95% CI 0.68-1.33, = 0.76).
Compared with placebo, randomization to fenofibrate was associated with lower rates of incident albuminuria and a slower eGFR decline, but no difference in incidence of CKD or kidney failure in ACCORD participants.
脂质代谢异常可能促使2型糖尿病患者慢性肾脏病(CKD)的发生和发展。非诺贝特可使估算肾小球滤过率(eGFR)早期出现可逆性降低,但它可能对糖尿病微血管并发症具有保护作用。我们推测,在糖尿病控制心血管风险行动(ACCORD)试验参与者中,随机分配至非诺贝特组与安慰剂组相比,对肾脏结局具有长期有益影响。
我们在ACCORD脂质试验中进行了一项分析,以研究随机分配至非诺贝特组与安慰剂组与eGFR变化以及微量白蛋白尿、大量白蛋白尿、CKD和肾衰竭发生时间之间的关联。
我们分析了非诺贝特组的2636名参与者和安慰剂组的2632名参与者。在中位随访4年期间,非诺贝特治疗与较低的eGFR下降率相关(非诺贝特组为每年每1.73平方米-0.28毫升/分钟,安慰剂组为每年每1.73平方米-1.25毫升/分钟,<0.01),且与较低的微量白蛋白尿发生率(风险比[HR]0.56,95%置信区间[CI]0.43-0.72,<0.001)和大量白蛋白尿发生率(HR 0.72,95%CI 0.57-0.91,<0.001)相关。CKD(HR 0.92,95%CI 0.74-1.15,=0.46)和/或肾衰竭(HR 0.95,95%CI 0.68-1.33,=0.76)的发生率没有差异。
与安慰剂相比,在ACCORD参与者中,随机分配至非诺贝特组与较低的蛋白尿发生率和较慢的eGFR下降相关,但CKD或肾衰竭的发生率没有差异。