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 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.