Uremic platelets?

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Have you ever been consulted to dialyze for a high BUN. Or have you ever been asked to comment on the high BUN’s effects on bleeding and platelet function. Here’s an interesting case report I came across in JASN that suggests that it’s not the urea alone that causes the problems.
Familial azotaemia is a rare autosomal dominant condition, first described in 1978, resulting from an impairment in urinary excretion of urea. The actual molecular defect is unclear at present.
The index case in this review is a 29-year-old woman, who has a 2-year-old male child and 34-year-old brother that appear to be affected. All are characterized by having urea clearances less than 5ml/min. The two adult patients are of short stature (approx 150cm each). All pedigree members had measured creatinine clearances in the 80-90ml/min range, normal haemoglobin values and unremarkable chemistries other than a high BUN of 100-120mg/dL in the adults and 70mg/dL in the child.
Bleeding times in the two adults were normal. The index case and her child both had further platelet function tests, including measurement of clotting times in response to ADH and epinephrine, which were all normal. In unpublished data from the child, they state that aggregation tests in response to collagen and arachidonic acid were irreversible, indicative of normal platelet function also.
This analysis certainly suggests that an isolated high urea per se is not a cause of platelet dysfunction. In renal failure perhaps it is other ‘uraemic toxins’ that cause the problems. Perhaps a high urea acts in concert with build-up of these other molecules. Further research will obviously be required to determine this.
In summary, there are huge deficiencies in our understanding of other toxins that accumulate in acute and chronic low clearance states, and the role they play in the symptoms, signs and pathophysiology of what we call ‘uraemia’.  But, the urea/BUN on it’s own? Probably not.


  1. Thanks for that,

    I've been looking for that article for a while.


  2. In response to Spiderman: I haven't had a chance to pull the article yet, but could this be what you're talking about:

    Mayo Clin Proc. 1972 Jan;47(1):21-9.

    Effects of urea loading in patients with far-advanced renal failure.
    Johnson WJ, Hagge WW, Wagoner RD, Dinapoli RP, Rosevear JW.

  3. guanidosuccinate is said to be responsible for platelet dysfunction…

  4. Great Post,

    Same is true with uremic s/s. There is an old article that I cant find now (and maybe someone can help me) but it was done by infusing urea in normal healthy volunteers!!

    With BUN at almost 200, there were no signs or symptoms of what we consider uremia. There is a lot that we need to figure out as to what constitutes 'uremia'

    Awesome post.

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