巴多昔芬甲基酯评估慢性肾病和2型糖尿病患者的基线特征：肾脏事件发生情况（BEACON）试验

Baseline characteristics in the Bardoxolone methyl EvAluation in patients with Chronic kidney disease and type 2 diabetes mellitus: the Occurrence of renal eveNts (BEACON) trial.

作者信息

Lambers Heerspink Hiddo J, Chertow Glenn M, Akizawa Tadao, Audhya Paul, Bakris George L, Goldsberry Angie, Krauth Melissa, Linde Peter, McMurray John J, Meyer Colin J, Parving Hans-Henrik, Remuzzi Giuseppe, Christ-Schmidt Heidi, Toto Robert D, Vaziri Nosratola D, Wanner Christoph, Wittes Janet, Wrolstad Danielle, de Zeeuw Dick

机构信息

Department of Clinical Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

出版信息

Nephrol Dial Transplant. 2013 Nov;28(11):2841-50. doi: 10.1093/ndt/gft445.

DOI:10.1093/ndt/gft445

PMID:24169612

Abstract

BACKGROUND

Type 2 diabetes mellitus (T2DM) is the most important contributing cause of end-stage renal disease (ESRD) worldwide. Bardoxolone methyl, a nuclear factor-erythroid-2-related factor 2 activator, augments estimated glomerular filtration. The Bardoxolone methyl EvAluation in patients with Chronic kidney disease and type 2 diabetes mellitus: the Occurrence of renal eveNts (BEACON) trial was designed to establish whether bardoxolone methyl slows or prevents progression to ESRD. Herein, we describe baseline characteristics of the BEACON population.

METHODS

BEACON is a randomized double-blind placebo-controlled clinical trial in 2185 patients with T2DM and chronic kidney disease stage 4 (eGFR between 15 and 30 mL/min/1.73 m(2)) designed to test the hypothesis that bardoxolone methyl added to guideline-recommended treatment including inhibitors of the renin-angiotensin-aldosterone system slows or prevents progression to ESRD or cardiovascular death compared with placebo.

RESULTS

Baseline characteristics (mean or percentage) of the population include age 68.5 years, female 43%, Caucasian 78%, eGFR 22.5 mL/min/1.73 m(2) and systolic/diastolic blood pressure 140/70 mmHg. The median urinary albumin:creatinine ratio was 320 mg/g and the frequency of micro- and macroalbuminuria was 30 and 51%, respectively. Anemia, abnormalities in markers of bone metabolism and elevations in cardiovascular biomarkers were frequently observed. A history of cardiovascular disease was present in 56%, neuropathy in 47% and retinopathy in 41% of patients.

CONCLUSIONS

The BEACON trial enrolled a population heretofore unstudied in an international randomized controlled trial. Enrolled patients suffered with numerous co-morbid conditions and exhibited multiple laboratory abnormalities, highlighting the critical need for new therapies to optimize management of these conditions.

摘要

背景

2型糖尿病（T2DM）是全球终末期肾病（ESRD）的最重要促成原因。巴多昔芬甲基，一种核因子红细胞2相关因子2激活剂，可提高估计的肾小球滤过率。慢性肾脏病和2型糖尿病患者中巴多昔芬甲基的评估：肾脏事件的发生（BEACON）试验旨在确定巴多昔芬甲基是否能减缓或预防ESRD的进展。在此，我们描述BEACON人群的基线特征。

方法

BEACON是一项针对2185例T2DM和慢性肾脏病4期（估算肾小球滤过率在15至30 mL/min/1.73 m²之间）患者的随机双盲安慰剂对照临床试验，旨在检验以下假设：与安慰剂相比，在包括肾素 - 血管紧张素 - 醛固酮系统抑制剂在内的指南推荐治疗基础上加用巴多昔芬甲基可减缓或预防ESRD进展或心血管死亡。

结果

该人群的基线特征（均值或百分比）包括年龄68.5岁，女性43%，白种人78%，估算肾小球滤过率22.5 mL/min/1.73 m²，收缩压/舒张压140/70 mmHg。尿白蛋白与肌酐比值中位数为320 mg/g，微量白蛋白尿和大量白蛋白尿的发生率分别为30%和51%。贫血、骨代谢标志物异常以及心血管生物标志物升高较为常见。56%的患者有心血管疾病史，47%有神经病变史，41%有视网膜病变史。