The objects of this research were to determine what relationship existed between the toxicity of various normal urinary constituents and the manifestations of what is clinically known as uremia—meaning by the term "uremia" the symptoms observed as a result of marked obstruction to the outflow of urine, on the one hand, and, on the other hand, the symptoms which appear in many cases of chronic Bright's disease, characterized by convulsions, various paralyses and coma.
In pursuance of these objects, it was thought advisable to begin with the simplest organic urinary constituent—urea—to determine its toxicity on dogs—when injected in large doses in relatively short periods of time—to note the symptoms produced, to follow the changes in the blood and urine content of urea, and to determine, at the necropsy, the pathologic changes that might have taken place—both gross and microscopic—as well as the urea content of various body fluids. Then, the
LEITER L. OBSERVATIONS ON THE RELATION OF UREA TO UREMIA. Arch Intern Med (Chic). 1921;28(3):331-354. doi:10.1001/archinte.1921.00100150096006