Monday, February 14, 2011

Take one glass of water, three times a day...

As mentioned previously by Nate, there is some evidence that lowering urine osmolarity below that of the serum can reduce the rate of growth of cysts in PCKD and thus preserve renal function. The rationale for this is that ADH stimulates cAMP production in the collecting duct and that this is required for cyst growth. Therefore, if you can reduce ADH secretion, you might be able to delay progression of the disease.
One potential therapeutic option is the use of vaptans. ADH receptor-antagonists have been used in the treatment of SIADH and heart failure and theoretically, they could be of some benefit in patients with PCKD. However,these medications are not cheap and I wonder how you could ensure that the patients drink enough water so as not to become hypernatremic.
A paper was published in CJASN this month that suggests a more physiological means of decreasing ADH secretion. The study included 8 patients with PCKD who had 24 hour collections to determine their mean daily excretion of osmoles as well as their urine volume and osmolarity. At the beginning of the study, the average urine Osm was 496 with a total volume of 1.5L. The aim of the study was to decrease the urine osmolarity to less than 285, thus making it hypo-osmolar and theoretically reducing ADH secretion.
Assuming that total urine osmoles would not vary much from day to day on a normal diet, the authors used the formula:
(Total urinary solutes/285) – baseline urine volume = V
to determine the amount of excess water each subject would have to drink to reduce the urine osmolarity to 285 or below.
On average, the subjects managed to increase their urine volumes to about 2.3L daily at the end of the study. The mean urine Osm decreased to 325 and 5/8 patients achieved the target of 285 or lower.
Although this by no means proves that it is an effective therapy for PCKD, the paper shows that urine Osm can be safely reduced in a targeted way without the use of medications.

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