Uremic Metabolites: Kidney Function Biomarkers

[Mike Lustgarten]

 

[Alex K Chen]

my p-cresol sulfate is 3.5646. yours is hella-elevated so idk what that means, but it seems to have some clinical significance

Quote

At the cellular level, p-cresol sulfate and other uremic toxins have been shown to induce the calcification of vascular smooth muscle cells (Hénaut et al. 2018). The mechanism involves the production of oxidative stress and inflammation, leading to a phenotypic switch from a contractile to a synthetic phenotype, including proliferation, senescence and calcification (Chang et al. 2020). In epithelial cells, p-cresol sulfate and indoxyl sulfate (a metabolite of tryptophan produced through bacterial fermentation in the intestine) are also thought to induce epithelial-to-mesenchymal transition, leading to fibrosis and calcification of the vessels (Opdebeeck et al. 2020).

 

indoxyl sulfate is 0.999 and trimethylamine n-oxide is 0.17275

 

 

Trigonelline

0.914189530755705

μM

 

1-Methylhistidine	1.34120022846978	μM
3-Methylhistidine	0.164850766300379	μM

 

trans-4-Hydroxyproline

3.65460096746473

μM

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362314/ has different [and higher] average values for p-cresol sulfate  (FOR A YOUNGER POPULATION).

For me, "Therefore, a concentration of 3.5646 μM p-cresol sulfate equates to 66.99 mg/dL." (this is between vegetarians and non-vegetarians). Mine could still be lower, but I am vegetarian and eat A LOT of fiber (and my tyrosine is 22.56, lower than the lower bound of normals at 30..)..

My 1-methylhistidine is also elevated, AS IS YOURS. The only study on this is https://academic.oup.com/aje/article/152/8/752/126819

and it says "vegetarians have lower levels". Idk what the hell this means b/c again, I'm hella vegetarian...

 

 

 

 

Edited August 20, 2023 by InquilineKea

[IgorF]

A year ago I did a similar but more simple test (well, more promoted ones are not easily available at my location) and afterwards scratched my head for a long time, trying to understand "warnings" from it. I normally follow the time-validated approach when first comes clinical picture and then in some cases tests are used to confirm or rule out things, moving on the decision tree, thus I know I don't have issues for which the test was designed and generally speaking it is a waste of money, but curiosity drives))

So for my increased p-cresol value I found these two things important to keep in mind (in the case there are no signs of clostridia overgrow which are hard to miss if there are such):

1.

https://www.biorxiv.org/content/10.1101/2020.11.10.374645v2.full
https://pubmed.ncbi.nlm.nih.gov/34468872/

p-cresol is produced from tyrosine and the day before the test I did not followed very strict dietary recomendations and I had 200% rda for tyrosine (or even more) from peanuts which are known to be lovely food for some gutizens.

2.

this is from some book on clostridia

https://books.google.com/books?id=lTfLBAAAQBAJ&pg=PA279&lpg=PA279&dq=There+has+been+significant+interest+in+the+development+of+rapid,+reliablelaboratory+tests+for+the+detection+of+C.+difficile+or+its+products.&source=bl&ots=doxgFDwK2S&sig=ACfU3U22w6mbC8Vcfsr0Q0A0lG-tgHST9Q&hl=en&sa=X&ved=2ahUKEwjUve6I1uuAAxVJEBAIHSeZCeEQ6AF6BAgEEAM#v=onepage&q=There has been significant interest in the development of rapid%2C reliablelaboratory tests for the detection of C. difficile or its products.&f=false
    

Quote

Other Laboratory Tests
    There has been significant interest in the development of rapid, reliable
    laboratory tests for the detection of C. difficile or its products. Early
    attempts evaluated direct gram stain of stool specimens. This technique,
    along with evaluation for white blood cells, has not been found to be
    either sensitive or specific (Shanholtzer et al., 1983). Direct detection of
    C. difficile in feces using gas-liquid chromatography has also been at-
    tempted (Levett, 1984). Levett concluded in a study of 110 stools (27
    positive for C. difficile) that gas-liquid chromatography for detection of
    volatile fatty acids or p-cresol in stool was an insensitive and nonspecific
    screening technique for the presence of C. difficile.

(bold is mine). I don't know if particular lab's way to detect p-cresol is better now but nevertheless, the case is exactly confirming the approach - no clinical picture -> no need for exotic and not widespread test.

p-cresol can't be produced by our methabolism alone but we have 1000 bacterias and I doubt we know enough about them, especially anaerobic for which we know so little due to technical complexity of their studies.

So I just taken into account the result but I will play this game again when such tests will cost tens of bucks and not hundreds.

Br,

Igor