Development and Use of an Isolated Perfused Kidney Model to Investigate Mechanisms of Renal Dysfunction Related to B. anthracis Edema and Lethal Toxins

在本研究中，我们首先建立了一个分离的大鼠肾脏灌流模型，以检测ET和LT对肾功能的直接影响。该模型可以独立于毒素对全身血流动力学功能的潜在影响来研究毒素对肾脏的影响。该模型将允许测量ET和LT对肾小球滤过率的影响；肾小管功能，包括钠和葡萄糖排泄以及重吸收、浓度和酸化；以及间质变化。 在到目前为止完成的研究中，我们发现ET，而不是像我们最初假设的那样刺激肾小管钠的损失，这种毒素实际上促进了自由水的吸收，并在较小程度上促进了钠的吸收。这种游离水摄取量的增加为严重炭疽感染患者的钠水平降低提供了一个基础，也可能导致患者出现明显的血管外液体收集。目前正在进行研究，以确定调节自由水吸收的机制。 这项研究的成果在2015年美国胸科学会国际会议上发表。

In the present study, we first developed an isolated perfused rat kidney model to examine the direct effects of ET and LT on renal function. This model allows investigation of the toxins' renal effects independent of their potential influence on systemic hemodynamic function. The model will permit measures of the effects of ET and LT on glomerular filtration rate; tubular function including sodium and glucose excretion as well as reabsorption, concentration and acidification; and interstitial changes. In studies completed thus far, we have discovered that ET, rather than stimulating renal tubular sodium losses as we originally hypothesized, this toxin actually promotes free water uptake and to a lesser degree sodium uptake. This increase in free water uptake provides one basis for the reduced sodium levels noted in patients with severe anthrax infection and may also contribute to the marked extravascular fluid collections patients develop. Studies are presently underway determining the mechanisms that mediate the free water uptake ET. Work from this study was presented at the 2015 International Conference of the American Thoracic Society.