Concept Map: Thiazide induced hyponatremias(TAH)

We see this form of hyponatremia in several cases, but recently there has been some newer findings on the mechanisms of TAH(*).  In one study published in JCI in 2017, Ware et al showed that there is a subset of patients with a genetic baseline( SLCO2A1 mutation) decrease in prostaglandin(PGE) transport activity which then becomes a risk factor for TAH.  So these patients have increased urinary PGE2 and low AVP levels leading to a pure "nephrogenic" cause of tubular water absorption and dilution hyponatremia. PGE2 is critical in insertion and removal of AQP2 channels in the apical membrane. Increased PGE2 signaling leads to insertion of AQP2 channels into membrane and increase water absorption in an ADH independent manner. This is fascinating. Perhaps then mechanism in NSAIDS as well?
Check out this amazing review in AJKD on this topic. 

TOPIC DISCUSSION: FUROSEMIDE in HYPERCALCEMIA

Treatment of symptomatic hypercalcemia is treating the underlying cause but also some symptomatic management.  Usually aggressive IV hydration is warranted sometimes even at 150-200-250 CC/HR.
Once volume depletion is addressed, a loop diuretic MAY be used for augmentation of calcium excretion.
A recent review and analysis published in Annals of Internal Medicine sheds some light about use of loop diuretic in this setting.
The review suggests the following points:

1. Aggressive hydration is necessary
2. Use of diuretics without aggressive hydration might be harmful
3. Found only 9 articles documenting the use of furosemide in hypercalcemia and latest one published in 1983 and total was only 37 patients.
4. Average dose was 1120mg over 24 hours ( really??)
5. Normalization of Ca occurred in only 14 of 39 cases
6. Study with lower doses didn't achieve normalization ( and what do we use????)
7. complications of other electrolyte disorders ensued
8. Finally, recommended against the use of this agent routinely except for cases of volume overloaded with hypercalcemia.
I think the tile of the paper listed below nicely puts it:- Furosemide in hypercalcemia is an unproven but common practice ( really not evidence based)

Ref: http://www.ncbi.nlm.nih.gov/pubmed/18711156