Uremia: A historical reappraisal of what happened
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Urea was identified as a urinary salt in 1662 and was the first organic bodily product to be synthesized <italic>in vitro</italic> in 1828. This heralded the end of an era that defined disease as an imbalance between vital life forces, and catalyzed the merging of organic chemical sciences into clinical medicine. The term <italic>urée</italic> (urea) was introduced in 1803, its accumulation in blood was dubbed <italic>urémie</italic> (uremia) in 1847, and the procedure for its removal from urine across semi-permeable membranes designated dialysis in 1861. The advent of modern dialysis in the 20th century provided lifesaving replacement therapy for the universally fatal disease that progressive uremia had been theretofore. Today, the clearance of urea is no longer used as a marker to identify patients with kidney disease; rather it has been adopted as a measure of the adequacy of dialysis, and the "urea toxicity" of yesteryears has been replaced by that of dialyzable "uremic toxins". As a result, the use of the term uremia has become non-uniform and is now applied to variable scenarios ranging from "azotemia" to "kidney failure" and to the symptoms persisting in patients receiving maintenance hemodialysis. In the process, the quest for variably dialyzed uremic toxins has overshadowed the consideration that dialysis is an invasive non-physiologic process that operates counter to normal homeostasis and itself may be toxic.
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