kidney stone question

[dark horse]

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What is the relationship of thiazides to kidney stones? My understanding is that it decreases urine calcium, and I also know that it causes hyperuricemia (through a similar mechanism to calcium reabsorption). If a patient has a radiolucent stone after having taken thiazides for several years, are they more likely to have cysteine or uric acid stones?

 

[Idiopathic]

thiazide administration will cause net reabsorption of calcium and is a first line pharmacotherapy for calcium stones. To answer your second question, I would say uric acid stones, since cysteine stones are rarer in nature (and arent they usually present at a very young age?)

 

[dreds]

the only thing that causes cystine stones is cystinuria (AR mutation). they usually present within the first two decades, but occasionally present later in life. they are radiolucent (contrary to one of the Q bank explanations), so you usually need a CT to find them.

hope this helps.

 

[dark horse]

I agree that cysteine stones should appear earlier in life and they are less likely becuase they are less common, but it also seems that thiazides would prevent and not cause uric acid stones in addition to calcium stones. On the question that I recently had I chose cysteine because thiazides lower both uric acid and calcium levels in the urine by promoting a net reabsorption - causing hyperuricemia and hypercalcemia. My thinking was that this change might precipitate a previously silent genetic mutation. Any other thoughts? 👍 👎

 

[woowoo]

thiazides cause hyperuricemia. just know this fact. we took our shelfs last week for all of our classes, and that question was on every single board with the exception of behavorial sciences.

 

[Idiopathic]

of course they do, and this is why they can precipitate gout. however, they are not indicated for treating uric acid stones, suggesing that their use does not lower the incidence, and urate stones are by far the first differential when presented with a radiolucent stone (assuming no hx of cysteine stones, which are very rare). thiazide diuretics do alkalinize the urine which can dissolve urate stones, but again, they are not indicated.

 

[BlackNDecker]

Bump...because this question has been bugging me.

I googled Thiazides and stones for an association with either Uric acid or cystine stones, but nothing came up.

 

[Idiopathic]

Bump...because this question has been bugging me.

I googled Thiazides and stones for an association with either Uric acid or cystine stones, but nothing came up.

exactly. the question is obvsiously testing you on whether you understand the thiazide/uricemia connection, but even with that said, no association has been shows between thiazide and reducing urate stones and so since urate stones are at least 2-3X more common than cysteine stones, that has to be the answer, especially in someone older than a child.

 

[exmike]

of course they do, and this is why they can precipitate gout. however, they are not indicated for treating uric acid stones, suggesing that their use does not lower the incidence, and urate stones are by far the first differential when presented with a radiolucent stone (assuming no hx of cysteine stones, which are very rare). thiazide diuretics do alkalinize the urine which can dissolve urate stones, but again, they are not indicated.

I'm not sure that is entirely correct. Gout is associated with uric acid stones, so long term thiazide use would lead to hyperuricemia as well as uric acid stones. Eventually the retained uric acid has to go somewhere (gout + uric acid stones).

 

[Idiopathic]

I'm not sure that is entirely correct. Gout is associated with uric acid stones, so long term thiazide use would lead to hyperuricemia as well as uric acid stones. Eventually the retained uric acid has to go somewhere (gout + uric acid stones).

No, thiazides dont create more uric acid they just inhibit secretion/promote reabsorption. They are neither a risk factor for nor a treatment for urate stones.

edit: btw, you may be right about the several years part, but i think urate stones usually have more to do with urine ph than with total amount of uric acid. Hell, I dont know, but what I do know is that the answer is probably uric acid stones 😉

 

[MDFACC]

hi, all this discussion has me a little confused. am i missing something in this logic:

the learning point is thiazides cause hyperuricemia by whatever mechanism-->excess uric acid in blood also relates to excess uric acid in the urinary collecting system-->excess presence here can lead to the formation of uric acid stones. did i simplify this too much?

cysteine stones can be caused by cysteinuria (reabsorption disease). and the pH is important for ammonium stones (struvite) that is favored by basic pH.

 

[Idiopathic]

hi, all this discussion has me a little confused. am i missing something in this logic:

the learning point is thiazides cause hyperuricemia by whatever mechanism-->excess uric acid in blood also relates to excess uric acid in the urinary collecting system-->excess presence here can lead to the formation of uric acid stones. did i simplify this too much?

cysteine stones can be caused by cysteinuria (reabsorption disease). and the pH is important for ammonium stones (struvite) that is favored by basic pH.

I think that you have the right answer and there are two ways to look at this.

1) long term HCTZ user still on diuretic will not have increased urinary uric acid because the mechanism is still in effect (the mechanism that causes proximal tubule reabsorption of uric acid), and anyway thiazide diuretics have not been shown to cause kidney stones, likely because they help alkalinize the urine, which is the actual way to rx these stones (although it is not considered a first or second-line pharmacotherapy).

2) uric acid stones are 2-3X more common than cysteine stones anyway. none of this changes that.

so right answer, debatable reasoning. im not for sure why, but like so many of these questions its pretty easy to reason the answer. keep in mind though, that this question would likely NEVER be on boards in this form without some ancillary information (CA patient on chemo, urate overproducer with acidic urinary pH...)

 

[exmike]

hi, all this discussion has me a little confused. am i missing something in this logic:

the learning point is thiazides cause hyperuricemia by whatever mechanism-->excess uric acid in blood also relates to excess uric acid in the urinary collecting system-->excess presence here can lead to the formation of uric acid stones. did i simplify this too much?

cysteine stones can be caused by cysteinuria (reabsorption disease). and the pH is important for ammonium stones (struvite) that is favored by basic pH.

Thiazides lead to volume depletion which increases sodium resorption in the proximal tubule. uric acid (along with almost everything else) follow sodium. Thats how you get hyperuricemia with thiazides.

 

[BlackNDecker]

uric acid (along with almost everything else) follow sodium. Thats how you get hyperuricemia with thiazides.

This is actually incorrect. There are specific transporters in the PCT dedicated to secreting organic acids. Unfortunately these transporters are not specific, and as a result ALL organic acids compete for secretion. This is the mechanism of Gout in alchoholics with lactic acidosis:

👍 Lactic acid --> Latic acid/Uric acid compete for secretion --> 👍 plasma uric acid --> gout

( 👍 = up arrow)

the learning point is thiazides cause hyperuricemia by whatever mechanism

This is also the mechanism of Thiazides in hyperuricemia. They have to be secreted into the tubule to work on the luminal Na/Cl transporter. Thus, they compete for the same organic acid transporter. <-- This is the learning point.

long term HCTZ user still on diuretic will not have increased urinary uric acid because the mechanism is still in effect

You don't honestly believe that increased plasma Uric acid WON'T inevitably result in increased filtered uric acid do you? FILTERED LOAD = GFR X [plasma]
Eventually, the level of uric acid in the plasma will overcome the competitive inhibition and a new set point will be established. Imagine the alternative, massively high levels of uric acid accumulate over years of usage. I could just hear their joints crackling when they walk

Idiopathic, where did you read that Thiazides alkalinize the urine? I have only read that they cause metabolic alkalosis. Hypokalemia results in increased activity of the K+/H+ATPase in Intercalated cells --> increased H+ in urine. The urine would therefore be slightly acidic, which coincidentally provides the optimum environment for uric acid stone formation...correct?


It would have been nice to know the PRECISE wording of the question 🙄

 

[MDFACC]

we got a future nephrologist ova here

 

[exmike]

This is actually incorrect. There are specific transporters in the PCT dedicated to secreting organic acids. Unfortunately these transporters are not specific, and as a result ALL organic acids compete for secretion. This is the mechanism of Gout in alchoholics with lactic acidosis:

👍 Lactic acid --> Latic acid/Uric acid compete for secretion --> 👍 plasma uric acid --> gout

( 👍 = up arrow)

That is only partially true. Uric acid is freely filtered at the glomerulus. And it does follow sodium.

 

[BlackNDecker]

we got a future nephrologist ova here

Ha...all credit goes to the 3 G's...God, Guyton, and Goljan (in that order). Everything I know I owe to these three gangstas of knowledge.

That is only partially true. Uric acid is freely filtered at the glomerulus. And it does follow sodium.

I think the purpose of the oranic acid transporters is that the charge and size of these acids prevents their free filtration. It is possible that uric acid secretion/reabsorption is coupled to Na+....however, my understanding is that it is NOT freely filtered.

 

[Idiopathic]

You don't honestly believe that increased plasma Uric acid WON'T inevitably result in increased filtered uric acid do you? FILTERED LOAD = GFR X [plasma]
Eventually, the level of uric acid in the plasma will overcome the competitive inhibition and a new set point will be established. Imagine the alternative, massively high levels of uric acid accumulate over years of usage. I could just hear their joints crackling when they walk

Idiopathic, where did you read that Thiazides alkalinize the urine? I have only read that they cause metabolic alkalosis. Hypokalemia results in increased activity of the K+/H+ATPase in Intercalated cells --> increased H+ in urine. The urine would therefore be slightly acidic, which coincidentally provides the optimum environment for uric acid stone formation...correct?


It would have been nice to know the PRECISE wording of the question 🙄

I think what we have all debated here is an interesting point. While you are right about the mechanism and likely right about the urine pH, but the risk factor for uric acid stone formation is, I believe extremely acidic pH (5 or less) (I didnt have a text handy, sorry 😛 ) we've all essentially come to the same conclusion, and it reinforces the point that this is not a very good USMLE question, because of the vague nature of the topic. Despite what you would like to think, there is no research that defines a link between thiazide diuretic use and uric acid or cysteine stone formation. We can extrapolate one, but since we are dealing with a test that must be backed up by scientific study to be valid, its highly unlikely that you would see a "suppose" type of question. High serum uric acid is a risk factor for uric acid stones, and its definitely reasonable to think that uric acid stones could result, and its reasonable to think that there is absolutely no way that it could increase the likelihood of cysteine stone formation. Either way you look at it, youre right.

I dont know, man I guess I better call up Poppy 😉

 

[beastmaster]

Thiazides have 2 mechanisms. First is competitive inhibition of excretion. Second, once diuretic in effect, volume depletion increases uric acid reabsorption from the proximal tubule.

In alcoholics, alcohol ingestion drops liver ATP, increasing AMP. Excess AMP is converted to uric acid. (In addition to competitive excretion).