BACKGROUND & PURPOSE It is well established that end-stage renal disease (ESRD) is associated with increased cardiovascular morbidity and mortality both in the adult and pediatric population. Although the underlying molecular mechanisms are poorly understood, compromised nitric oxide (NO) bioactivity has been suggested as a contributing factor. With this in mind, we investigated the effects of hemodialysis on NO homeostasis and bioactivity in blood. METHODS & RESULTS Plasma and dialysate samples were obtained before and after hemodialysis sessions from adults (n = 33) and pediatric patients (n = 10) with ESRD on chronic renal replacement therapy, and from critically ill adults with acute kidney injury (n = 12) at their first sustained low-efficiency dialysis session. Levels of nitrate, nitrite, cyclic guanosine monophosphate (cGMP) and amino acids relevant for NO homeostasis were analyzed. We consistently found that nitrate and cGMP levels in plasma were significantly reduced after hemodialysis, whereas post-dialysis nitrite and amino acids coupled to NO synthase activity (i.e., arginine and citrulline) were only significantly reduced in adults with ESRD. The amount of excreted nitrate and nitrite during dialysis were similar to daily endogenous levels that would be expected from endothelial NO synthase activity. CONCLUSIONS Our results show that hemodialysis significantly reduces circulating levels of nitrate and cGMP, indicating that this medical procedure may impair NO synthesis and potentially NO signaling pathways.

中文翻译：

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“在终末期肾脏疾病中通过血液透析去除硝酸盐和亚硝酸盐，在急性肾损伤中通过持续低效率透析去除硝酸盐和亚硝酸盐”。

背景与目的众所周知，终末期肾脏疾病（ESRD）与成人和儿童人群的心血管发病率和死亡率增加有关。尽管对潜在的分子机制了解甚少，但已建议一氧化氮（NO）的生物活性受损是其促成因素。考虑到这一点，我们调查了血液透析对血液中NO稳态和生物活性的影响。方法与结果从接受慢性肾脏替代治疗的成人（n = 33）和儿科患者（n = 10）接受ESRD治疗的成人和小儿患者（n = 10）以及急性肾损伤危重患者（n = 12）的血液透析前后获得血浆和透析液样品）进行第一次低效率透析。硝酸盐，亚硝酸盐，分析了环鸟苷一磷酸（cGMP）和与NO稳态相关的氨基酸。我们一致发现血液透析后血浆中硝酸盐和cGMP水平显着降低，而透析后亚硝酸盐和与NO合酶活性偶联的氨基酸（即精氨酸和瓜氨酸）仅在ESRD成人中显着降低。透析过程中排出的硝酸盐和亚硝酸盐的量与内皮一氧化氮合酶活性预期的每日内源性水平相似。结论我们的结果表明血液透析显着降低了硝酸盐和cGMP的循环水平，表明该医疗程序可能会损害NO的合成和潜在的NO信号通路。我们一致发现血液透析后血浆中硝酸盐和cGMP水平显着降低，而透析后亚硝酸盐和与NO合酶活性偶联的氨基酸（即精氨酸和瓜氨酸）仅在ESRD成人中显着降低。透析过程中排出的硝酸盐和亚硝酸盐的量与内皮一氧化氮合酶活性预期的每日内源性水平相似。结论我们的结果表明血液透析显着降低了硝酸盐和cGMP的循环水平，表明该医疗程序可能会损害NO的合成和潜在的NO信号通路。我们一致发现血液透析后血浆中硝酸盐和cGMP水平显着降低，而透析后亚硝酸盐和与NO合酶活性偶联的氨基酸（即精氨酸和瓜氨酸）仅在ESRD成人中显着降低。透析过程中排出的硝酸盐和亚硝酸盐的量与内皮一氧化氮合酶活性预期的每日内源性水平相似。结论我们的结果表明血液透析显着降低了硝酸盐和cGMP的循环水平，表明该医疗程序可能会损害NO的合成和潜在的NO信号通路。透析过程中排出的硝酸盐和亚硝酸盐的量与内皮一氧化氮合酶活性预期的每日内源性水平相似。结论我们的结果表明血液透析显着降低了硝酸盐和cGMP的循环水平，表明该医疗程序可能会损害NO的合成和潜在的NO信号通路。透析过程中排出的硝酸盐和亚硝酸盐的量与内皮一氧化氮合酶活性预期的每日内源性水平相似。结论我们的结果表明血液透析显着降低了硝酸盐和cGMP的循环水平，表明该医疗程序可能会损害NO的合成和潜在的NO信号通路。