Allopurinol. Kidney stones.

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Don Saklad - 13 Apr 2004 00:27 GMT

How is Allopurinol which is purported to alter purine uric acid
production related to stone formation of calcium oxylate crystals?...

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Hillary Israeli - 13 Apr 2004 02:16 GMT

*How is Allopurinol which is purported to alter purine uric acid
*production related to stone formation of calcium oxylate crystals?...

Allopurinol inhibits xanthine oxidase, reducing the conversion of
hypoxanthine and xanthine to uric acid and resulting in direct inhibition
of purine biosynthesis due to elevated oxypurine concentration (negative
feedback). Oxypurinol also inhibits xanthine oxidase. So anyway you have
dramatically decreased uric acid concentrations, decreased renal tubular
transport of uric acid, and then the side effect of increased tubular
reabsorption of calcium. I would think that the increased absorbtion of
calcium is a big reason for decreased CaOx crystalluria. I could of course
be wrong. My biochemistry professor never wanted to answer my questions
because he was pissed off I hadn't studied biochem undergrad. At least
that was my perception.

-h.

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hillary israeli vmd http://www.hillary.net info@hillary.net
"uber vaccae in quattuor partes divisum est."
not-so-newly minted veterinarian-at-large :)

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Gregory Poon - 13 Apr 2004 03:49 GMT

It isn't immediately clear to me how the renal transport of uric acid is
coupled to Ca; they are oppositely charged and so any coupled transport
would involve symport, presumably reabsorption out of the lumen into the
tubular cells. The reduction in oxalate stones may be just physical
chemistry -- CaOx may precipitate more readily in the presence of uric acid
microcrystals. This is consistent with the observation that kidney stones
are usually mixed uric acid/oxalate/phosphate and that hyperuricemia is a
risk factor for CaOx stones.

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Gregory M. K. Poon, Ph.D., R.Ph., B.Sc.Phm.
Departments of Pharmaceutical Sciences and Chemical Engineering
University of Toronto
Toronto, ON M5S 2S2

> *How is Allopurinol which is purported to alter purine uric acid
> *production related to stone formation of calcium oxylate crystals?...
[quoted text clipped - 12 lines]
>
> -h.

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Hillary Israeli - 16 Apr 2004 02:56 GMT

*It isn't immediately clear to me how the renal transport of uric acid is
*coupled to Ca; they are oppositely charged and so any coupled transport
*would involve symport, presumably reabsorption out of the lumen into the
*tubular cells.

Well, it isn't immediately clear to me either, but I'm reasonably sure
that it exists. By which I mean I'm sure that decreased tubular transport
of uric acid results in increased renal reabsorption of calcium and
decreased calcium excretion. I couldn't tell you WHY it does, but it does.
At least, that's what I was told! :)

-h.

Signature

hillary israeli vmd http://www.hillary.net info@hillary.net
"uber vaccae in quattuor partes divisum est."
not-so-newly minted veterinarian-at-large :)

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Gregory Poon - 16 Apr 2004 04:13 GMT

> Well, it isn't immediately clear to me either, but I'm reasonably sure
> that it exists. By which I mean I'm sure that decreased tubular transport
> of uric acid results in increased renal reabsorption of calcium and
> decreased calcium excretion. I couldn't tell you WHY it does, but it does.
> At least, that's what I was told! :)

Do you mean uric acid tubular *reabsorption* out of the lumen or *secretion*
into the lumen? The fact that transporter blockers like probenecid increase
renal clearance of uric acid means that uric acid is net reabsorbed renally.
However to maintain electroneutrality, these oppositely charged ions have to
move in the same direction. So now we've run into a contradiction.
Hmmm.....

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Gregory M. K. Poon, Ph.D., R.Ph., B.Sc.Phm.
Departments of Pharmaceutical Sciences and Chemical Engineering
University of Toronto
Toronto, ON M5S 2S2

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