Department of Surgery, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), Instituto do Coração (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil.
Clinics (Sao Paulo). 2023 May 29;78:100222. doi: 10.1016/j.clinsp.2023.100222. eCollection 2023.
Clinical reports associate kidneys from female donors with worse prognostic in male recipients. Brain Death (BD) produces immunological and hemodynamic disorders that affect organ viability. Following BD, female rats are associated with increased renal inflammation interrelated with female sex hormone reduction. Here, the aim was to investigate the effects of sex on BD-induced Acute Kidney Injury (AKI) using an Isolated Perfused rat Kidney (IPK) model.
Wistar rats, females, and males (8 weeks old), were maintained for 4h after BD. A left nephrectomy was performed and the kidney was preserved in a cold saline solution (30 min). IPK was performed under normothermic temperature (37°C) for 90 min using WME as perfusion solution. AKI was assessed by morphological analyses, staining of complement system components and inflammatory cell markers, perfusion flow, and creatinine clearance.
BD-male kidneys had decreased perfusion flow on IPK, a phenomenon that was not observed in the kidneys of BD-females (p < 0.0001). BD-male kidneys presented greater proximal (p = 0.0311) and distal tubule (p = 0.0029) necrosis. However, BD-female kidneys presented higher expression of eNOS (p = 0.0060) and greater upregulation of inflammatory mediators, iNOS (p = 0.0051), and Caspase-3 (p = 0.0099). In addition, both sexes had increased complement system formation (C5b-9) (p=0.0005), glomerular edema (p = 0.0003), and nNOS (p = 0.0051).
The present data revealed an important sex difference in renal perfusion in the IPK model, evidenced by a pronounced reduction in perfusate flow and low eNOS expression in the BD-male group. Nonetheless, the upregulation of genes related to the proinflammatory cascade suggests a progressive inflammatory process in BD-female kidneys.
临床报告表明，女性供体的肾脏在男性受者中预后较差。脑死亡（BD）会产生免疫和血液动力学紊乱，影响器官活力。BD 后，雌性大鼠的肾脏炎症增加，与雌性性激素减少有关。在这里，目的是使用离体灌流大鼠肾脏（IPK）模型研究性别对 BD 诱导的急性肾损伤（AKI）的影响。
Wistar 大鼠，雌性和雄性（8 周龄），在 BD 后维持 4 小时。进行左肾切除术，并将肾脏保存在冷盐溶液中（30 分钟）。在 37°C 的体温下进行 IPK，使用 WME 作为灌流溶液。通过形态分析、补体系统成分和炎症细胞标志物染色、灌流流量和肌酐清除率评估 AKI。
BD 雄性肾脏的 IPK 灌流流量降低，而 BD 雌性肾脏则没有观察到这种现象（p < 0.0001）。BD 雄性肾脏的近端（p = 0.0311）和远端肾小管（p = 0.0029）坏死更严重。然而，BD 雌性肾脏的 eNOS 表达更高（p = 0.0060），炎症介质 iNOS（p = 0.0051）和 Caspase-3（p = 0.0099）的上调更明显。此外，两种性别均有补体系统形成（C5b-9）增加（p = 0.0005）、肾小球水肿（p = 0.0003）和 nNOS 表达增加（p = 0.0051）。
本研究数据揭示了 IPK 模型中肾脏灌注的重要性别差异，BD 雄性组灌流液流量明显减少，eNOS 表达降低。然而，与促炎级联相关的基因上调提示 BD 雌性肾脏中存在进行性炎症过程。
