Department of Nephrology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Am J Physiol Renal Physiol. 2019 Sep 1;317(3):F519-F528. doi: 10.1152/ajprenal.00606.2018. Epub 2019 Jun 26.
Mineralocorticoid receptor antagonism prevents acute kidney injury induced by ischemia-reperfusion in rodent and pig preclinical models. In a pilot study, we showed that spironolactone (25 mg) reduced oxidative stress after 5 days of kidney transplant (KT). In the present study, we investigated the effects of higher doses (50 and 100 mg) of spironolactone on kidney function, tubular injury markers, and oxidative stress in living donor KT recipients. We included KT recipients aged 18 yr or older who received immunosuppression therapy with IL-2 receptor antagonist, mycophenolate mofetil, corticosteroids, and tacrolimus with negative cross-match, and compatible blood group. Patients were randomized to receive placebo ( = 27), spironolactone (50 mg, = 25), or spironolactone (100 mg, = 25). Treatment was given from 3 days before and up to 5 days after KT. Serum creatinine, K, urine neutrophil gelatinase-associated lipocalin-2, heat shock protein 72, and 8-hydroxy-2-deoxyguanosine levels were assessed. As expected, kidney function was improved after KT. Serum K remained in the normal range along the study. There was no significant effect of spironolactone on urinary neutrophil gelatinase-associated lipocalin-2 levels, whereas the increase in urinary heat shock protein 72 levels tended to be less intense in the 100 mg spironolactone-treated group ( = 0.054). In the placebo-treated group, urinary 8-hydroxylated-guanosine levels increased on and after transplantation. This effect was prevented in patients that received spironolactone. In conclusion, spironolactone reduces the acute increase in urinary oxidative stress in living donor KT recipients.
醛固酮受体拮抗剂可预防啮齿动物和猪临床前模型的缺血再灌注引起的急性肾损伤。在一项初步研究中，我们发现螺内酯（25 毫克）可减少肾移植后 5 天的氧化应激。在本研究中，我们研究了更高剂量（50 和 100 毫克）的螺内酯对活体供肾移植受者肾功能、肾小管损伤标志物和氧化应激的影响。我们纳入了接受白细胞介素-2 受体拮抗剂、霉酚酸酯、皮质类固醇和他克莫司免疫抑制治疗的年龄在 18 岁或以上的肾移植受者，这些受者交叉配型阴性，血型相容。患者随机分为安慰剂组（ = 27）、螺内酯（50 毫克， = 25）或螺内酯（100 毫克， = 25）组。治疗从肾移植前 3 天开始，持续至肾移植后 5 天。评估血清肌酐、钾、尿中性粒细胞明胶酶相关脂质运载蛋白-2、热休克蛋白 72 和 8-羟基-2-脱氧鸟苷水平。正如预期的那样，肾移植后肾功能得到改善。血清钾在整个研究期间保持在正常范围内。螺内酯对尿中性粒细胞明胶酶相关脂质运载蛋白-2 水平没有显著影响，而在 100 毫克螺内酯治疗组，尿热休克蛋白 72 水平的升高趋势较弱（ = 0.054）。在安慰剂治疗组中，尿 8-羟基鸟苷水平在移植后第 天和第 天增加。这种作用在接受螺内酯治疗的患者中得到了预防。总之，螺内酯可降低活体供肾移植受者急性尿氧化应激的增加。
