TOXICITY OF UREA AND ITS ROLE IN THE PATHOGENESIS OF UREMIA*

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Abstract
High concentrations of urea (540-1,690 mg %) were maintained in the extracellular fluid of nephrectomized dogs by means of intermittent peritoneal lavage. This technique permits the maintenance of the other components of the extracellular fluid constant and thus allows one to study the specific effects of urea. High concentrations or urea induce many of the symptoms encountered in uremia which have been attributed hitherto to changes other than the accumulation of urea. Of the various symptoms observed in the late stages of chronic renal failure, it would appear from the present observations that many of these previously attributed to some unknown catabolite accumulating in the uremic patient may be due to the effect of the accumulated urea previously looked upon as an innocuous agent. The presence of high urea levels also induces certain dislocations of the electrolyte composition of the tissues which are responsible for, or at least are accompaniments of, the disruptive effects of urea on the components of the tissue cells to which presumably it owes its toxicity.