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

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Abstract

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 we have shown that ET, rather than stimulating renal tubular sodium losses as we originally hypothesized, actually promotes free water uptake and to a lesser degree sodium uptake. Immunohistochemistry studies and urine analysis show ET mediates these renal effects via up regulation of aquaporin 2 in the tubular membrane. This increase in free water uptake with ET 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. Work from this study was presented at the 2015 International Conference of the American Thoracic Society and a manuscript has been submitted and is presently under review.