title: Short-Term Tolvaptan Increases Water Intake and Effectively Decreases Urinary Calcium Oxalate, Calcium Phosphate and Uric Acid Supersaturations.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
authors.forename: Wisit
authors.initials: W
authors.lastname: Cheungpasitporn
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Erickson
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Rule
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Felicity
authors.initials: F
authors.lastname: Enders
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. Electronic address: lieske.john@mayo.edu.
authors.forename: John C
authors.initials: JC
authors.lastname: Lieske
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists / Q000008:administration & dosage; D001552:Benzazepines / Q000008:administration & dosage*; D015415:Biomarkers / Q000652:urine; D002129:Calcium Oxalate / Q000652:urine*; D002130:Calcium Phosphates / Q000652:urine*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004326:Drinking / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007010:Hyponatremia; D007669:Kidney Calculi / Q000517:prevention & control* / Q000652:urine; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013997:Time Factors; D000077602:Tolvaptan; D016896:Treatment Outcome; D014527:Uric Acid / Q000652:urine*; D055815:Young Adult
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D015415:Biomarkers; D002130:Calcium Phosphates; D000077602:Tolvaptan; D002129:Calcium Oxalate; D014527:Uric Acid; C020243:calcium phosphate
keywords: kidney calculi; osmolar concentration; vasopressins; water-electrolyte balance