title: Alkali replacement raises urinary citrate excretion in patients with topiramate-induced hypocitraturia.
abstract: OBJECTIVE
  The aims of this study were to assess (1) the magnitude and temporality of decreased urinary citrate excretion in patients just starting topiramate and (2) the effect of alkali replacement on topiramate-induced hypocitraturia.
  
  
  METHODS
  Study 1 was a prospective, non-intervention study in which patients starting topiramate for headache remediation provided pre- and post-topiramate 24 h urine collections for measurement of urine citrate. Study 2 was a clinical comparative effectiveness study in which patients reporting to our stone clinic for kidney stones and who were treated with topiramate were prescribed alkali therapy. Pre- and post-alkali 24 h urinary citrate excretion was compared.
  
  
  RESULTS
  Data for 12 and 22 patients (studies 1 and 2 respectively) were evaluated. After starting topiramate, urinary citrate excretion dropped significantly by 30 days (P = 0.016) and 62% of patients had hypocitraturia (citrate <320 mg day(-1) ). At 60 days, urine citrate was even lower than at baseline (P = 0.0032) and 86% of patients had developed hypocitraturia. After starting alkali, urine citrate increased in stone-forming patients on topiramate (198 ± 120 to 408 ± 274 mg day(-1) ; P = 0.042 for difference). 85% of patients were hypocitraturic on topiramate alone vs. 40% after adding alkali. The increase in urinary citrate was greater in patients provided ≥ 90 mEq potassium citrate.
  
  
  CONCLUSIONS
  Our study is the first to provide clinical evidence that alkali therapy can raise urinary citrate excretion in patients who form kidney stones while being treated with topiramate. Clinicians should consider alkali therapy for reducing the kidney stone risk of patients benefitting from topiramate treatment for migraine headaches or other conditions.
authors: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors: R Allan
authors: RA
authors: Jhagroo
authors: Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors: Margaret L
authors: ML
authors: Wertheim
authors: Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors: Kristina L
authors: KL
authors: Penniston
mesh_terms: D000328:Adult; D000468:Alkalies; D019343:Citric Acid / Q000652:urine*; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D007669:Kidney Calculi / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D019357:Potassium Citrate / Q000627:therapeutic use*; D011446:Prospective Studies; D000077236:Topiramate
chemical_list: D000468:Alkalies; D000077236:Topiramate; D019343:Citric Acid; D005632:Fructose; D019357:Potassium Citrate
keywords: alkali replacement; citrate; headache; nephrolithiasis; topiramate; urolithiasis