盐皮质激素受体拮抗剂对蛋白尿及慢性肾脏病进展的影响：一项系统评价与荟萃分析
Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: a systematic review and meta-analysis.
作者信息
Currie Gemma, Taylor Alison H M, Fujita Toshiro, Ohtsu Hiroshi, Lindhardt Morten, Rossing Peter, Boesby Lene, Edwards Nicola C, Ferro Charles J, Townend Jonathan N, van den Meiracker Anton H, Saklayen Mohammad G, Oveisi Sonia, Jardine Alan G, Delles Christian, Preiss David J, Mark Patrick B
机构信息
Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Center, 126 University Place, Glasgow, UK.
Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
出版信息
BMC Nephrol. 2016 Sep 8;17(1):127. doi: 10.1186/s12882-016-0337-0.
BACKGROUND
Hypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney function declines in many patients. Aldosterone excess is a risk factor for progression of kidney disease. Hyperkalaemia is a concern with the use of mineralocorticoid receptor antagonists. We aimed to determine whether the renal protective benefits of mineralocorticoid antagonists outweigh the risk of hyperkalaemia associated with this treatment in patients with chronic kidney disease.
METHODS
We conducted a meta-analysis investigating renoprotective effects and risk of hyperkalaemia in trials of mineralocorticoid receptor antagonists in chronic kidney disease. Trials were identified from MEDLINE (1966-2014), EMBASE (1947-2014) and the Cochrane Clinical Trials Database. Unpublished summary data were obtained from investigators. We included randomised controlled trials, and the first period of randomised cross over trials lasting ≥4 weeks in adults.
RESULTS
Nineteen trials (21 study groups, 1 646 patients) were included. In random effects meta-analysis, addition of mineralocorticoid receptor antagonists to renin angiotensin system inhibition resulted in a reduction from baseline in systolic blood pressure (-5.7 [-9.0, -2.3] mmHg), diastolic blood pressure (-1.7 [-3.4, -0.1] mmHg) and glomerular filtration rate (-3.2 [-5.4, -1.0] mL/min/1.73 m(2)). Mineralocorticoid receptor antagonism reduced weighted mean protein/albumin excretion by 38.7 % but with a threefold higher relative risk of withdrawing from the trial due to hyperkalaemia (3.21, [1.19, 8.71]). Death, cardiovascular events and hard renal end points were not reported in sufficient numbers to analyse.
CONCLUSIONS
Mineralocorticoid receptor antagonism reduces blood pressure and urinary protein/albumin excretion with a quantifiable risk of hyperkalaemia above predefined study upper limit.
背景
高血压和蛋白尿在慢性肾脏病进展中起关键作用。尽管使用肾素 - 血管紧张素系统抑制剂进行治疗，但许多患者的肾功能仍会下降。醛固酮增多是肾病进展的一个危险因素。高钾血症是使用盐皮质激素受体拮抗剂时需要关注的问题。我们旨在确定在慢性肾脏病患者中，盐皮质激素拮抗剂的肾脏保护益处是否超过与此治疗相关的高钾血症风险。
方法
我们进行了一项荟萃分析，研究盐皮质激素受体拮抗剂在慢性肾脏病试验中的肾脏保护作用和高钾血症风险。从MEDLINE（1966 - 2014年）、EMBASE（1947 - 2014年）和Cochrane临床试验数据库中识别试验。未发表的汇总数据从研究者处获得。我们纳入了随机对照试验以及成人中持续≥4周的随机交叉试验的第一阶段。
结果
纳入了19项试验（21个研究组，1646例患者）。在随机效应荟萃分析中，在肾素 - 血管紧张素系统抑制基础上加用盐皮质激素受体拮抗剂导致收缩压较基线降低（-5.7 [-9.0, -2.3] mmHg）、舒张压降低（-1.7 [-3.4, -0.1] mmHg）以及肾小球滤过率降低（-3.2 [-5.4, -1.0] mL/min/1.73 m²）。盐皮质激素受体拮抗作用使加权平均蛋白/白蛋白排泄减少38.7%，但因高钾血症退出试验的相对风险高出三倍（3.21，[1.19, 8.71]）。死亡、心血管事件和严重肾脏终点事件的报告数量不足以进行分析。
结论
盐皮质激素受体拮抗作用可降低血压和尿蛋白/白蛋白排泄，但高钾血症风险高于预定义研究上限且可量化。
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