title: Vitamin B6 in primary hyperoxaluria I: first prospective trial after 40 years of practice.
abstract: OBJECTIVE
  Primary hyperoxaluria type I (PH I) is caused by deficiency of the liver-specific enzyme alanine-glyoxylate:aminotransferase (AGT). Many mutations are known to perturb AGT protein folding. Vitamin B6 (B6) is the only specific drug available for treatment. Although B6 has been used for >40 years, controlled data on B6 efficacy are lacking. Therefore, this study investigated the absolute and relative change of urinary oxalate (Uox) excretion under increasing dosages of B6, the first prospective trial to do so.
  
  
  METHODS
  B6 response was studied in 12 patients (7 male patients) with genetically confirmed PH I (3 Gly170Arg homozygous, 5 compound Gly170Arg and/or Phe152Ile heterozygous, and 4 negative for Gly170Arg and/or Phe152Ile mutations) and noncompromised renal function. Efficacy was defined as a 30% relative reduction in Uox excretion. B6 was administered orally starting at 5 mg/kg body weight per day and given in increments of 5 mg/kg every 6 weeks, up to a final dosage of 20 mg/kg per day at week 24. Uox and serum B6 levels were measured every 6 weeks.
  
  
  RESULTS
  Mean relative Uox reduction was 25.5%. Uox declined from 2.09±0.55 (mean±SD) at baseline to 1.52±0.60 mmol/1.73 m(2) per day (P=0.01) at week 24. Serum B6 levels increased from 22.5±8.7 to 1217±776 ng/ml (P<0.001). Six patients showed a ≥30% relative reduction of Uox at week 24.
  
  
  CONCLUSIONS
  This first prospective trial confirmed B6 efficacy in 50% of patients (three of three homozygous, one of five heterozygous, and two of four patients negative for the Gly170Arg and/or Phe152Ile mutations). Interestingly, no complete biochemical remission was observed, even in the homozygous Gly170Arg study participants. Future trials are necessary to learn more about genotype-related B6 response and B6 metabolism.
authors.affiliation: Division of Pediatric Nephrolgy and, †Pediatric Clinical Trial Unit, Department of Pediatrics and Adolescents Medicine, University Hospital Cologne, Cologne, Germany;, ‡Institute of Medical Statistics, Informatics and Epidemiology, and, §Institute of Human Genetics, University of Cologne, Cologne, Germany, ‖Department of Pediatrics, Division of Pediatric Nephrology, University Hospital Bonn, Bonn, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Hoyer-Kuhn
authors.forename: Sina
authors.initials: S
authors.lastname: Kohbrok
authors.forename: Ruth
authors.initials: R
authors.lastname: Volland
authors.forename: Jeremy
authors.initials: J
authors.lastname: Franklin
authors.forename: Barbara
authors.initials: B
authors.lastname: Hero
authors.forename: Bodo B
authors.initials: BB
authors.lastname: Beck
authors.forename: Bernd
authors.initials: B
authors.lastname: Hoppe
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D015415:Biomarkers / Q000652:urine; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D005858:Germany; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006960:Hyperoxaluria, Primary / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000652:urine; D008297:Male; D009154:Mutation; D019815:Oxalic Acid / Q000652:urine*; D010641:Phenotype; D011446:Prospective Studies; D013997:Time Factors; D000637:Transaminases / Q000235:genetics; D016896:Treatment Outcome; D025101:Vitamin B 6 / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood
chemical_list: D015415:Biomarkers; D025101:Vitamin B 6; D019815:Oxalic Acid; D000637:Transaminases; C019635:Alanine-glyoxylate transaminase