SAN DIEGO—Tolvaptan dramatically increases urine volume and decreases urinary concentrations of kidney stone-forming solutes in calcium stone formers, according to study findings presented at Kidney Week.

“The findings of our study suggest that tolvaptan may have a potential role in the management of nephrolithiasis,” said investigator Wisit Cheungpasitporn, MD, of the Mayo Clinic in Rochester, Minn., who presented the findings. “However, because we assessed the short-term effect, further study is needed to determine if long term use if V2 receptor antagonists results in fewer stone events.”

Dr. Cheungpasitporn, along with senior author John C. Lieske, MD, and other collaborators at Mayo, enrolled 21 adult calcium kidney stone formers (10 formed calcium oxalate stones and 11 formed calcium phosphate stones). The investigators randomly assigned patients to receive tolvaptan 45 mg/day or placebo for week 1, followed by washout week 2, then crossover to drug or placebo for week 3. The researchers assessed 24-hour urine volume and chemistries at the end of week 1 and week 3.

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The researchers reasoned that tolvaptan, a V2 receptor antagonist that blocks water reabsorption in the collecting duct, should increase serum osmolality and stimulate thirst and water intake, with the net effect of lowering supersaturation of stone-forming salts.

Results showed that tolvaptan significantly decreased urinary osmolality compared with placebo (204 vs. 529 mOsm/kg), but the majority of urinary salt excretion rates (in mg/24 hours), including sodium and calcium, did not change significantly. Consequently, urinary calcium oxalate and calcium phosphate supersaturation decreased significantly. Urinary uric acid also decreased significantly. The tolvaptan treatment effect did not differ significantly between calcium oxalate and calcium phosphate stone types. Serum sodium increased slightly while on tolvaptan.

The authors concluded that their study highlights the dramatic benefit that increased free water ingestion alone can have on urinary supersaturation.