Uremia (or uraemia for my friends from the Empire) results from kidney failure. Accumulated wastes build up in the blood, resulting in a number of symptoms; these symptoms include loss of appetite, vomiting, headache, rashes, abnormal body odor, bleeding (due to platelet problems), and coma. The term “uremia” comes from “urea" which is a nitrogenous waste product measured in the blood. Elevations in urea usually reflect poor kidney function, but a number of other conditions may raise blood urea nitrogen (BUN) levels independent of kidney function. These include high protein diets, catabolic states such as sepsis, gastrointestinal bleeding, and a number of drugs (glucocorticoids most notably).
In general, BUN correlates well with uremic symptoms, but urea is not the cause of these symptoms itself. Supporting data comes primarily from a study of urea loading in chronic dialysis patients. Patients studied still had abnormal kidney function, so while high levels of urea did not result in “uremia” in otherwise well-dialyzed patients, other abnormalities could not be studied.
Thanks to a Brief Communication in the May issue of Journal of the American Society of Nephrology (JASN) we now know that uremic platelet dysfunction is not due to urea.
Linthorst, Avis, and Levi studied platelet function in vivo and in vitro from 3 family members with familial azotemia. In this rare inherited disorder, blood urea levels rise to levels consistent with uremia but without reduction in glomerular filtration rate or accompanying uremic symptoms. All platelet studies fell within the normal range, ruling-out urea itself as the cause of platelet dysfunction.
Sometimes I am asked to dialyze patients with high BUN levels but relatively normal glomerular filtration rates to help with bleeding or other uremic possibilities. Now we know that lowering BUN is not itself beneficial because it is merely a biochemical epiphenomenon, not the real toxin. All thanks to an experiment of nature.