Saturday, April 30, 2011

NKF Spring Clinical Meeting - Calcium reabsorption

Here are some points from one of the cases presented at the electrolyte workshop this afternoon:

The major teaching point was that the reabsorption of calcium closely follows that of sodium. Therefore, in sodium avid states, calcium tends to be reabsorbed also – conversely, in natriuretic states, calcium tends to be lost in the urine.

What about thiazides – they are associated with hypercalcaemia and hypocalciuria, but what is the mechanism there?
In the distal convoluted tubule, thiazides act by blocking the luminal Na/Cl cotransporter. There is also a luminal calcium channel called TRPV5, which allows calcium to be reabsorbed in the DCT via a transcellular route. Overall, this is felt to contribute around 15% of total tubular calcium reabsorption. It was thought that this channel might have played a role in the pathogenesis of thaizide-induced hypercalcaemia.

However, when they created a knock-out mice without TRPV5 and treated them with thiazides, hypercalcaemia still developed. So, it would appear that the mechanism simply involves decreased extracellular volume caused by the diuretics, leading to increased sodium reabsorption more proximally and consequent enhanced proximal calcium absorption. See this review.

Of note, the paracellular route for calcium reabsorption in the thick ascending limb is guarded by tight junctions between the cells. These are made up of proteins called Claudins. Genetic defects in Claudin proteins have been associated with impaired calcium reabsorption and subsequent hypercalciuria and stone formation, giving us some insight into the molecular level of calcium handling by the kidney.

This was a great meeting with lots of interesting discussions and talks. Roll on next year in Washington!


Dr. Helbert Rondón said...

The study you mentioned published in JCI with the TRPV5 knock-down model concluded the mechanism of hypocalciuria is increase in calcium reabsorption in the proximal tubule and not in the TAL. This is the link for the article:

Finnian Mc Causland said...

Corrected - thanks for the link.