Department of Anesthesiology and Operative Intensive Care Medicine, Campus Virchow-Klinikum and Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Department of Experimental Medicine, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany.
PLoS One. 2019 Jun 17;14(6):e0218308. doi: 10.1371/journal.pone.0218308. eCollection 2019.
Acute kidney injury (AKI) corrupts the outcome of about 50% of all critically ill patients. We investigated the possible contribution of the pathology acidemia on the development of AKI. Pigs were exposed to acidemia, acidemia plus hypoxemia or a normal acid-base balance in an experimental setup, which included mechanical ventilation and renal replacement therapy to facilitate biotrauma caused by extracorporeal therapies. Interestingly, extensive histomorphological changes like a tubular loss of cell barriers occurred in the kidneys after just 5 hours exposure to acidemia. The additional exposure to hypoxemia aggravated these findings. These 'early' microscopic pathologies opposed intra vitam data of kidney function. They did not mirror cellular or systemic patterns of proinflammatory molecules (like TNF-α or IL 18) nor were they detectable by new, sensitive markers of AKI like Neutrophil gelatinase-associated lipocalin. Instead, the data suggest that the increased renal proton excretion during acidemia could be an 'early' first hit in the multifactorial pathogenesis of AKI.
急性肾损伤 (AKI) 会影响约 50%的所有重症患者的预后。我们研究了病理酸中毒对 AKI 发展的可能影响。在一个实验设置中，猪暴露于酸中毒、酸中毒加低氧血症或正常酸碱平衡状态下，包括机械通气和肾脏替代治疗，以促进体外治疗引起的生物创伤。有趣的是，仅仅暴露于酸中毒 5 小时后，肾脏就会发生广泛的组织形态学变化，如肾小管细胞屏障丧失。进一步暴露于低氧血症会加重这些发现。这些“早期”微观病理学与肾功能的活体数据相反。它们既不反映细胞或全身的促炎分子（如 TNF-α 或 IL-18）模式，也不能通过 AKI 的新的、敏感标志物如中性粒细胞明胶酶相关脂质运载蛋白检测到。相反，数据表明，酸中毒期间肾脏质子排泄增加可能是 AKI 多因素发病机制中的“早期”第一个打击。
