Short-Term Tolvaptan Increases Water Intake and Effectively Decreases Urinary
Calcium Oxalate, Calcium Phosphate and Uric Acid Supersaturations
#MMPMID26598423
Cheungpasitporn W
; Erickson SB
; Rule AD
; Enders F
; Lieske JC
J Urol
2016[May]; 195
(5
): 1476-1481
PMID26598423
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PURPOSE: Some patients cannot effectively increase water intake and urine volume
to prevent urinary stones. Tolvaptan, a V2 receptor antagonist, blocks water
reabsorption in the collecting duct and should decrease urinary supersaturation
of stone forming solutes, although this action has never been proved. MATERIALS
AND METHODS: We conducted a double-blind, randomized, placebo controlled,
crossover study of 21 calcium urinary stone formers stratified into majority
calcium oxalate (10 patients) and calcium phosphate (11) groups. Patients
received 45 mg tolvaptan per day or placebo for 1 week, followed by a washout
week and crossover to tolvaptan or placebo for week 3. A 24-hour urine sample was
collected at the end of weeks 1 and 3. RESULTS: Tolvaptan vs placebo decreased
urinary osmolality (mean ± SD 204 ± 96 vs 529 ± 213 mOsm/kg, p <0.001) and
increased urinary volume (4.8 ± 2.9 vs 1.8 ± 0.9 L, p <0.001). The majority of
urinary solute excretion rates, including sodium and calcium, did not change
significantly, although oxalate secretion increased slightly (from mean ± SD 15 ±
8 to 23 ± 8 mg per 24 hours, p = 0.009). Mean ± SD urinary calcium oxalate
supersaturation (-0.01 ± 1.14 vs 0.95 ± 0.87 dG, p <0.001), calcium phosphate
supersaturation (-1.66 ± 1.17 vs -0.13 ± 1.02 dG, p <0.001) and uric acid
supersaturation (-2.05 ± 4.05 vs -5.24 ± 3.12 dG, p = 0.04) all dramatically
decreased. Effects did not differ between the calcium oxalate and calcium
phosphate groups (p >0.05 for all interactions). CONCLUSIONS: Tolvaptan increases
urine volume and decreases urinary supersaturation in calcium stone formers.
Further study is needed to determine if long-term use of V2 receptor antagonists
results in fewer stone events.
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