Tuesday, March 30, 2010


Urine AQP2 excretion is increased by dehhydration
  2 (10%)
Urinary AQP2 is augmented in SIADH
  4 (21%)
The predominant aquaporin in the proximal tubule is AQP1
  1 (5%)
AQP2 is predominantly found in the S3 segment of the proximal tubules
  6 (31%)
V2 receptor antagonists can be used to treat X linked congenital Nephrogenic Diabetes Insipidus
  6 (31%)

Which statement above is false?
Tough question. It seems like it was between the last two choices.  Aquaporins in renal diseases and physiology are important to know about. A nice review was recently published in Nature
Review Nephrology, please all read. Its an exceptional review.  
***The AQP we really care most about is AQP2, the water channel found in the urinary surface of the principal cells of the collecting duct. Hence answer 4 is the right answer as that statement is false.
***The most prominent aqp in the s3 segment of the proximal tubule is aqp7 and in general Aqp1 is the most abundant in the proximal tubule. Aqp3 and 4 are also found on principal cells but in the basolateral
***The AQP2 is the one that is effected the most in all causes of Diabetes Insipidus(DI). Few recent studies have shown that urinary AQP2 excretion can give a clue of what is the WATER 
status of our patients.  It is associated with ADH activity indirectly.  
***You want more water to be absorbed in hypernatremic and severe dehydration sates and hence there will be more production and movement of AQP2 channels in the apical membrane in those instances and hence increased urinary production of them as well.  
So dehydration increases AQP2 in the urine and hydration decreases it. Augmentation of AQP2 is also found in SIADH and hence more water is absorbed and compounds the problem. Even in CHF patients, AQP2 activity is enchanced. 
***The last statement is interesting and its true. Most patients with congenital X-linked nephrogenic DI have defective V2 vasopressin receptors 
that are unable to properly fold intracellularly and, as a consequence, correctly transfer to the cell surface. In in vitro systems, the administration of selective, cell permeable nonpeptide 
V2 and V1a receptor antagonists were able to rescue mutant V2 receptors by promoting their proper folding and maturation . This resulted in the expression of functional cell surface V2 receptors.
lIn a pilot study, a nonpeptide V1a receptor antagonist was administered to five men with nephrogenic 
DI (each with one of three identified mutations in the V2 gene that codes for the V2 receptor)
lThis resulted in an increase in urine osmolality from a mean of 100 to 150 mosm/kg, and reductions in urine volume from 12 to 8 L/day and in water intake from 11 to 7 L/day.
lMost aquaporin-2 mutations associated with nephrogenic DI also result in proteins being retained in the intracellular space
lResearch to find chaperone-like molecules to help direct these proteins to the cell surface is ongoing.


  1. great post..
    wonder if we have tried to use aquaretics in lithium associated NDI

  2. Lithium causes via a cAMp mechanism a decrease in production and movement of the AQP2 channels to the apical membrane. The aquaretics are going to be V2 receptor antagonists.
    I think they might make things worse and worsen the DI.
    Am I missing anything?


All Posts

Search This Blog