What is the origin of the term uremia?
Much of our understanding of the pathophysiology of diseases comes from the analysis of body fluids that were being introduced into medicine in the 19th century. These early biochemical studies were instrumental in shaping much of the subsequent nomenclature and progress in the study of diseases in general and that of the end-stage kidney disease described by Richard Bright (1789–1858) at about that time.
Large volumes were necessary for the rather crude analytic methods available then, and it was generally easier to use the readily accessible and substantial quantities of urine rather than blood. Of the various chemical substances that were identified in the urine, it was probably that of urea which contributed most to what followed. First characterized as a “urinary salt” in 1662 and an “unusual saponaceous salt residue of urine that tasted different than sea salt” in 1732, urea was finally isolated as a pure salt by the Frenchmen François Fourcroy (1755–1809) and Nicolas Vaquelin (1763–1829) in 1799. By 1817 the properties, appearance, and chemical reactions of urea were described by the Englishman William Prout (1785–1850), who alluded to its presence in the blood. Shortly thereafter, in 1828 the German Friederich Wöhler (1800–1882) synthesized urea from two inorganic molecules, ammonia and cyanic acid, which prompted him to write triumphantly to his mentor Jöns Jacob Berzelius (1779–1848): “I can make urea without the use of kidney, either man or dog.” This was a major breakthrough and turning point in the history of science that placed the notion of vitalism, which had dominated medical concepts theretofore, to rest and validated the chemical approach to biology that was to launch the new basic sciences of organic chemistry and biochemistry. Wöhler’s discovery literally coincided with the description of Bright disease. Within a year, Robert Christison (1797–1882) reported increased urea levels in the serum of patients with Bright disease, which by 1847 led to the introduction by Pierre Piorry (1794–1879) of the term urémie (uremia), literally urine in the blood, to describe patients with high blood urea levels.
Over the years, the term uremia has come to encompass all the clinical manifestations of the failing kidneys. The sole role of urea to account for the symptom complex of uremic patients with advanced kidney disease was questioned from the outset. George Johnson (1818–1896), a contemporary of Richard Bright and a prominent authority on kidney disease who described the microscopic changes of Bright disease, wrote in 1852, “It is in the highest degree probable that urea is a poisonous agent, but we have no proof that it is more so than other urinary constituents which must be retained or accumulated in the blood, when the kidneys are so much disorganized as they are often found to be.” A truth that still holds, notwithstanding which the uremia of Piorry remains in use to this day as a rather vague and catch-all medical term used to refer to abnormalities of kidney failure that remain unexplained and presumed to result from the still elusive chemical product(s) that should have been excreted by the kidneys.
Of note, it was the continued studies of urea that were to provide much of the experimental and theoretic concepts that led to the discovery of the artificial kidney. It was the studies of Thomas Graham (1805–1869) on the diffusion and osmotic properties of urea that laid the very conceptual foundations of hemodialysis, and it is the proportional clearance of urea from the body by dialysis (urea reduction ratio) that now provides a measure of the adequacy of dialysis in treating patients with kidney failure.
It was also studies on the clearance of urea that paved the way to the study of kidney function, introduced the concept of renal efficiency, and provided for the classification of kidney disease. Early studies of progressive ablation of kidney mass to produce uremia were refined by measurement of blood levels of urea and its renal clearance in patients with kidney disease by George Widal (1862–1929) in France and Hermann Strauss (1864–1944) in Germany. Widal meticulously evaluated the gradual retention of nitrogenous end products ( azotémie ), which he went on to classify as azotemia that is alarming, grave, and fatal, the first classification of kidney diseases based on the severity of lost kidney function.
