Thiazides and renal stones

[Ezekiel20]

Dear all

For the last hour or so I've been struggling to understand this.

I've read my textbooks, searched the net, and emailed my prof, but I'd like an answer ASAP if any of you know it.

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It seems that the most common cause of hypercalcemia is the use of thiazide diuretics (which increase Ca reabsorption at the early distal tubule). And one of the manifestations of hypercalcemia is renal stones.
http://www.aafp.org/afp/20030501/1959.html

But at the same time, thiazides are used to TREAT patients with renal stones resulting from hypercalciuria.

e-medicine: "If the hypercalciuria is controlled successfully with dietary modification, continue therapy and repeat testing periodically. If unsuccessful, consider a trial of thiazide therapy."
http://www.emedicine.com/med/topic1069.htm

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So if you had a patient presenting with renal stones from hypercalciuria, you might prescribe thiazides which reduce Ca level in urine (thus preventing further episodes), but at the same time it might cause hypercalcemia in the patient, causing another renal stone...???

It seems that the thiazides move the Ca from the urine to the blood, so the patient will end up with renal stones regardless of whether the Ca level is high in the urine (hypercalciuria), or in the blood (hypercalcemia).

Man I am so confused.. somebody help me out please?

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[Hernandez]

More appropriately than saying hypercalcemia causes renal stones, you should say, hyperurocalcemia. so the way you treat too much calcium in the urine, is by retaining it and not excreting as much all the time, therefore preventing high urine calcium levels and decreasing the formation of stones.

 

[Ezekiel20]

More appropriately than saying hypercalcemia causes renal stones, you should say, hyperurocalcemia. so the way you treat too much calcium in the urine, is by retaining it and not excreting as much all the time, therefore preventing high urine calcium levels and decreasing the formation of stones.

Alright, so you're saying that if a patient is excreting too much Ca in their urine and forming renal stones, you put him/her on thiazides which makes them retain some Ca in their blood, thus preventing stone formation.

Would I be right in saying that if the same patient continued to use thiazides for a long time, it would eventually lead to hypercalcemia (high Ca in blood), and form renal stones..?

If I'm on the right track, the aim of thiazide therapy is to reach that middle ground when the patient is neither hypercalcemic nor hypercalciuric?

Thanks in advance

 

[Nerdoscience]

It's as simple as this: Thiazides keep Calcium out of the kidney and in the blood. Therefore, you don't get kidney stones, but you do get hypercalcemia.

Loop diuretics do the opposite. So they can treat hypercalcemia, but can also give you kidney stones.

Get it? It's the hypercalciuria that causes the stones, which is caused by excess excretion of calcium.

 

[Ezekiel20]

It's as simple as this: Thiazides keep Calcium out of the kidney and in the blood. Therefore, you don't get kidney stones, but you do get hypercalcemia.

Loop diuretics do the opposite. So they can treat hypercalcemia, but can also give you kidney stones.

Get it? It's the hypercalciuria that causes the stones, which is caused by excess excretion of calcium.

Sorry, but I don't think you understood my initial question.

You are right in saying that hypercalciuria causes renal stones, which you can treat with thiazides (so that Ca will be retained in the blood and not as much is present in the urine), but this matter is complicated by the fact that thiazides can cause hypercalcemia, which in turn causes renal stones.

http://www.aafp.org/afp/20030501/1959.html

See table 2 in this article, which states that one of the manifestations of hypercalcemia is renal stones.

So my initial question was how the same drug could be used to treat renal stones, but then again it can cause renal stones at the same time.

i.e. renal stones from hypercalciuria -> thiazide therapy -> hypercalcemia -> renal stones from hypercalcemia

I think the answer lies in the fact that you can treat hypercalciuria with thiazides, but the patient will not necessarily develop hypercalcemia unless the thiazide use is prolonged.

So, a patient with hypercalciuria has too much Ca in the urine. When treated with thiazides it can reduce Ca in the urine and retain it in the blood. However with prolonged thiazide use, it can tip the balance to the other side, and cause hypercalcemia which again causes renal stones.

 

[ANCAdoc]

I don't recall reading in a urology or nephrology article that thiazide diuretics cause hypercalcemia that may ultimately cause urinary calculi. The article you cite states "The most important renal effects are polydipsia and polyuria resulting from nephrogenic diabetes insipidus, and nephrolithiasis resulting from HYPERCALCIURIA". So the hypercalcemia translates into hypercalciuria, except with a thiazide you reduce the amount excreted (a cycle). No doubt, thiazides MAY cause MILD hypercalcemia, but I don't think to the level that correlates with stone disease. Thiazides have been proven in prospective clinical trials to reduce calcium stone formation.

Thus, you are right that if a patient has (idiopathic) hypercalcuria then giving a thiazide would increase distal tubular reabsorption AND reduce intestinal calcium reabsorption which means reduced Ca in the urine (and also blood!). But, the mild (if any) hypercalcemia that develops is not sufficient to form stones.

 

[Ezekiel20]

I don't recall reading in a urology or nephrology article that thiazide diuretics cause hypercalcemia that may ultimately cause urinary calculi. The article you cite states "The most important renal effects are polydipsia and polyuria resulting from nephrogenic diabetes insipidus, and nephrolithiasis resulting from HYPERCALCIURIA". So the hypercalcemia translates into hypercalciuria, except with a thiazide you reduce the amount excreted (a cycle). No doubt, thiazides MAY cause MILD hypercalcemia, but I don't think to the level that correlates with stone disease. Thiazides have been proven in prospective clinical trials to reduce calcium stone formation.

Thus, you are right that if a patient has (idiopathic) hypercalcuria then giving a thiazide would increase distal tubular reabsorption AND reduce intestinal calcium reabsorption which means reduced Ca in the urine (and also blood!). But, the mild (if any) hypercalcemia that develops is not sufficient to form stones.

Thanks for that. I've had the opportunity to ask my prof this morning (it's 11am here in Aus), and this was confirmed.