Effect of Intensive Blood Pressure Lowering on Kidney Tubule Injury: Findings From the ACCORD Trial Study Participants
Effect of Intensive Blood Pressure Lowering on Kidney Tubule Injury: Findings From the ACCORD Trial Study Participants
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DOI：
10.1053/j.ajkd.2018.07.016
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发表时间：
2019-01-01
影响因子：
13.2
通讯作者：
Coca, Steven G.
中科院分区：
文献类型：
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作者：
Nadkarni, Girish N.;Chauhan, Kinsuk;Coca, Steven G.
理由和目标：在控制糖尿病心血管风险行动（ACCORD-BP）试验中，与强度较低的血压目标（收缩压< 140 mm Hg）相比，随机分配到强度较低的血压（BP）降低（收缩压<120 mm Hg）导致估计肾小球滤过率（eGFR）下降更快。这是否反映了血流动力学效应或内在的肾损伤尚不清楚。研究设计：临床试验参与者亚组的纵向分析。设置和参与者：ACCORD-BP中529名参与者的亚组。暴露：肾小管损伤的尿液生物标志物（肾损伤分子1，白细胞介素18 [IL-18]），修复（人软骨糖蛋白39 [YKL-40]）和炎症结果：eGFR从基线到2年的变化。分析方法：结果：在529名参与者中，260名被随机分配到强化BP组，269名被随机分配到标准BP组，平均年龄为62 ± 6.5岁，eGFR为90 mL/min/1.73 m（2）。BP治疗组之间的基线临床特征、eGFR、尿白蛋白-肌酐比值（ACR）和尿生物标志物水平相似。与强度较低的BP治疗组相比，第2年时，强度BP治疗组的eGFR低9.2 mL/min/1.73 m2。尽管eGFR降低，但在该治疗组中，ACR降低30%，第2年时4种尿生物标志物水平不变或降低。同样在该组中，eGFR下降最大的参与者尿IL-18和YKL-40水平下降幅度更大。在一项对发生慢性肾脏疾病的参与者进行的亚组分析中（持续下降30%且eGFR < 60 mL/min/1.73 m（2）; n = 77），强化治疗组的ACR和4种生物标志物水平均未增加，而1种生物标志物IL-18的水平在不太强化的治疗组中增加。局限性：少数参与者基线患有晚期慢性肾脏疾病。治疗组之间的比较并不代表治疗组之间的比较，仅通过randomization.Conclusions创建：在一个子集的ACCORD-BP试验参与者，密集的BP控制与eGFR的减少，但不与损伤标志物水平的增加。这些结果支持在雅阁参与者中观察到的强化BP目标的eGFR下降可能主要反映了血流动力学改变。
Rationale & Objective: Random assignment to intensive blood pressure (BP) lowering (systolic BP < 120 mm Hg) compared to a less intensive BP target (systolic BP < 140 mm Hg) in the Action to Control Cardiovascular Risk in Diabetes BP (ACCORD-BP) trial resulted in a more rapid decline in estimated glomerular filtration rate (eGFR). Whether this reflects hemodynamic effects or intrinsic kidney damage is unknown.Study Design: Longitudinal analysis of a subgroup of clinical trial participants.Settings & Participants: A subgroup of 529 participants in ACCORD-BP.Exposures: Urine biomarkers of tubular injury (kidney injury molecule 1, interleukin 18 [IL-18]), repair (human cartilage glycoprotein 39 [YKL-40]), and inflammation (monocyte chemoattractant protein 1) at baseline and year 2.Outcomes: Changes in eGFR from baseline to 2 years.Analytical Approach: We compared changes in biomarker levels and eGFRs across participants treated to an intensive versus less intensive BP goal using analysis of covariance.Results: Of 529 participants, 260 had been randomly assigned to the intensive and 269 to the standard BP arm. Mean age was 62 +/- 6.5 years and eGFR was 90 mL/min/1.73 m(2). Baseline clinical characteristics, eGFRs, urinary albumin-creatinine ratios (ACRs), and urinary biomarker levels were similar across BP treatment groups. Compared to less intensive BP treatment, eGFR was 9.2 mL/min/1.73 m(2) lower in the intensive BP treatment group at year 2. Despite the eGFR reduction, within this treatment group, ACR was 30% lower and 4 urinary biomarker levels were unchanged or lower at year 2. Also within this group, participants with the largest declines in eGFRs had greater reductions in urinary IL-18 and YKL-40 levels. In a subgroup analysis of participants developing incident chronic kidney disease (sustained 30% decline and eGFR < 60 mL/min/1.73 m(2); n = 77), neither ACR nor 4 biomarker levels increased in the intensive treatment group, whereas the level of 1 biomarker, IL-18, increased in the less intensive treatment group.Limitations: Few participants with advanced baseline chronic kidney disease. Comparisons across treatment groups do not represent comparisons of treatment arms created solely through randomization.Conclusions: Among a subset of ACCORD-BP trial participants, intensive BP control was associated with reductions in eGFRs, but not with an increase in injury marker levels. These findings support that eGFR decline observed with intensive BP goals in ACCORD participants may predominantly reflect hemodynamic alterations.