Nephrology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Am J Nephrol. 2013;37(5):481-90. doi: 10.1159/000350539. Epub 2013 Apr 30.
Previous experimental studies from our laboratory have demonstrated that aldosterone plays a central role in renal ischemic processes. This study was designed to evaluate the effect of mineralocorticoid receptor blockade in renal transplant recipients from living donors.
20 adult kidney transplant recipients from living donors were included in a double-blind, randomized, placebo-controlled clinical pilot study that compared spironolactone and placebo. Placebo or spironolactone (25 mg) was administered 1 day before and 3 days posttransplantation. Renal function and urinary kidney injury molecule-1, interleukin-18, and heat shock protein 72 as well as urinary hydrogen peroxide (H2O2) levels were quantified.
No significant differences were seen between the groups studied regarding age, gender, indication for kidney transplantation, residual renal function, renal replacement therapy, or warm and cold ischemia periods. In contrast, spironolactone administration significantly reduced the oxidative stress assessed by the urinary H2O2 excretion, in spite of no differences in renal function or reduction in tubular injury biomarkers.
The findings of this exploratory study strongly suggest that aldosterone promotes oxidative stress and that the administration of spironolactone reduces the production of urinary H2O2 as a result of lesser formation of surrogate reactive oxygen species secondary to the ischemia-reperfusion phenomenon.
本实验室先前的实验研究表明,醛固酮在肾缺血过程中起核心作用。本研究旨在评估从活体供体肾移植受者中阻断盐皮质激素受体的效果。
20 名来自活体供体的成年肾移植受者纳入一项双盲、随机、安慰剂对照的临床试点研究,该研究比较了螺内酯和安慰剂的效果。在移植前 1 天和移植后 3 天给予安慰剂或螺内酯(25mg)。定量检测肾功能和尿肾损伤分子 1、白细胞介素 18 和热休克蛋白 72 以及尿过氧化氢(H2O2)水平。
研究组之间在年龄、性别、肾移植适应证、残余肾功能、肾脏替代治疗或热缺血和冷缺血时间方面无显著差异。相比之下,螺内酯的给药显著降低了尿 H2O2 的氧化应激,尽管肾功能或肾小管损伤生物标志物没有差异。
这项探索性研究的结果强烈表明,醛固酮促进氧化应激,而螺内酯的给药减少了尿 H2O2 的产生,这是由于缺血再灌注现象导致替代活性氧的形成减少。