Why are kidney stones so interesting?
Because the tubules > glomeruli

Disagree if you like, but it’s true.

A short thread on some mechanisms associated with calcium stones...

#nephtwitter #FOAMed #MedEd #uronephrology #kidneystone #nephrolith

Which is a risk factor for calcium oxalate stones?

Correct!

Risk factors for calcium oxalate stones classically include hypercalciuria and hyperoxaluria along with low urine volume.

#Hypercalciuria can stem from a LOT of different causes and clinical settings. The most common in adults is idiopathic.

There is debate about whether hyperuricosuria can serve as a nidus for CaOx stones.

https://pubmed.ncbi.nlm.nih.gov/18059457/ 

Hypocitraturia and high urine pH (>7.0) tend to be stronger risk factors for CaP stones (we’ll discuss that later!)

Photo courtesy of @porische

What is the link between hypercalciuria and salt (NaCl) intake?

Right! More NaCl --> Urine Calcium

How does this happen?!
The kidney has the answer.

In the proximal tubule, Ca reabsorption is linked with Na reabsorption.

With more Na reabsorption, H2O follows paracellularly and “drags” Ca along with it. #solventdrag

In the DCT, increased Na delivery reduces the stimulus for Na/Ca exchange on the basolateral membrane

This results in less Ca influx via TRVP5 channel.

If you understand this, you understand why normal saline is effective in hypercalcemia.

https://pubmed.ncbi.nlm.nih.gov/27009338/ 

Now, what is the link between hypercalciuria and acidosis?

Essentially besides leaching Ca from bones, acidosis uncouples Na reabs from Ca reabs in the DCT.

In acidosis,
PT: Na and Ca reabs linked
DCT: LESS Ca influx due to inhibition of TRPV5 and reduced TRPV5 mRNA due to H+

Net effect: more UrCa

https://pubmed.ncbi.nlm.nih.gov/27468975/ 

In the work up of hypercalciuria in calcium stone formers, it is important to consider monogenetic causes (esp in pediatrics)

https://pubmed.ncbi.nlm.nih.gov/15689405/ 
https://pubmed.ncbi.nlm.nih.gov/18446382/ 
https://pubmed.ncbi.nlm.nih.gov/18836558/ 

When the initial screen and/or work up are negative, we’re stuck with idiopathic hypercalciuria.

You may ask, should you counsel patients to reduce Ca intake to reduce risk of Ca stones and hypercalciuria?!

Correct, you should not.

Calcium intake has been found to reduce risk of stone formation likely by binding intestinal oxalate and reducing oxalate absorption.

https://pubmed.ncbi.nlm.nih.gov/8441427/ 

But, (a) #PUSHing fluid increases urine volume (ie lower the concentration of urinary calcium and reduce the relative supersaturation)

Coffee, tea, wine, beer, high citrate juices seem ok.

https://twitter.com/lieske_john/status/1334890304617541633
https://pubmed.ncbi.nlm.nih.gov/23676355/ 

Encourage low salt diet (UrNa goal < 80-100 mEq per day) and consider thiazide diuretics.

https://pubmed.ncbi.nlm.nih.gov/20042524/ 

Hope that helps the next time you have a calcium stone former with hypercalciuria.

Suggestions/comments are always welcome! #uronephrology #kidneystone #nephrolith

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