Monday, November 2, 2009

On the mechanism of thiazide-induced hypocalciuria

Back from the 2009 ASN Meeting in San Diego!  I'll admit to a few lapses in blogging, but the meeting kept me pretty busy.  Thanks to everybody who stopped by the Renal Fellow Network poster and their encouraging words.
The 2009 ASN Homer Smith Award went to Rene Bindels, a master physiologist from the Netherlands who has made great advances in our understanding of renal calcium and magnesium handling via the Trp channels.  Amongst the highlights of his Saturday morning talk was a good explanation for why hypocalciuria results from thiazide diuretic treatment.  

The hypocalciuric effect of thiazide diuretics is well-known:  we frequently put patients prone to develop calcium nephrolithiasis on thiazides with this effect in mind, and patients with Gitelman's Syndrome (caused by mutations in the thiazide-sensitive Na channel, NCC) also have significant hypocalciuria.  There were two general mechanisms postulated to account for this.  Either:

(1).  blockage of NCC results in increased active Ca uptake via TrpV5 channels in the distal tubule, or
(2). thiazide-induced hypovolemia results in enhanced passive Ca uptake in the proximal convoluted tubule.  

The generation of TrpV5 knockout mice provided an opportunity to see which of these possibilities was correct.  Interestingly, these mice still developed hypocalciuria when given thiazide diuretics, indicating that hypocalciuria does NOT require TrpV5 (that is, the 2nd explanation above is true while the 1st explanation is not).  Just another example of how the physiology in one segment of the nephron strongly influences the ion uptake in another segment.  


Rene C Bakker, The Netherlands said...

Dear Nathan,
why hypocalcemia results from thiazide diuretic treatment.

should be

why hypocalciuria results from thiazide diuretic treatment.

maybe it is possible to change this

nathanhellman said...

thanks, I made the change.

nathanhellman said...
This comment has been removed by the author.
Anonymous said...

if volume contraction promotes proxomal tubular reabsoriton of Ca in HCTZ ttreated patient then why it dosent happen with lasix