title: Efficacy and safety of Oxalobacter formigenes to reduce urinary oxalate in primary hyperoxaluria.
abstract: BACKGROUND
  Primary hyperoxaluria (PH) is a rare genetic disease, in which high urinary oxalate (Uox) cause recurrent kidney stones and/or progressive nephrocalcinosis, often followed by early end-stage renal disease, as well as extremely high plasma oxalate, systemic oxalosis and premature death. Oxalobacter formigenes, an anaerobic oxalate degrading bacterium, naturally colonizes the colon of most humans. Orally administered O. formigenes (Oxabact) was found to significantly reduce urine and plasma oxalate. We aimed to evaluate its effect and safety in a randomized, double-blind, placebo-controlled multicenter study.
  
  
  METHODS
  Oral Oxabact was given to PH patients (>5 years old, Uox > 1.0 mmol/1.73 m(2)/day, glomerular filtration rate (GFR) > 50 mL/min) at nine PH referral sites worldwide. Primary endpoint was the change from baseline in Uox (mmol/1.73 m(2)/day) after 24 weeks of treatment (>20% reduction).
  
  
  RESULTS
  Of the 43 subjects randomized, 42 patients received either placebo (23 subjects) or Oxabact (19 subjects). The change in Uox was <20% and not different between groups (P = 0.616). Ad hoc analysis was performed in 37 patients compliant with medication and urine processing. Change in Uox was -19% in subjects given Oxabact and -10% in placebo, (P = 0.288), but -21 and -7% with Uox expressed as molar creatinine ratio (Ox:Cr, mmol/mol, P = 0.06). Reduction of Ox:Cr was more obvious for patients with higher baseline values (>160 mmol/mol, Oxabact -28%, placebo -6%; P < 0.082). No serious adverse events were reported.
  
  
  CONCLUSIONS
  Oxabact was safe and well tolerated. However, as no significant change in Uox was seen, further studies to evaluate the efficacy of Oxabact treatment are needed.
authors: Division of Paediatric Nephrology, Department of Paediatric and Adolescent Medicine, University Hospital Cologne, Cologne, Germany. bernd.hoppe@uk-koeln.de
authors: Bernd
authors: B
authors: Hoppe
authors: Jaap W
authors: JW
authors: Groothoff
authors: Sally-Anne
authors: SA
authors: Hulton
authors: Pierre
authors: P
authors: Cochat
authors: Patrick
authors: P
authors: Niaudet
authors: Markus J
authors: MJ
authors: Kemper
authors: George
authors: G
authors: Deschênes
authors: Robert
authors: R
authors: Unwin
authors: Dawn
authors: D
authors: Milliner
mesh_terms: D000284:Administration, Oral; D000368:Aged; D003404:Creatinine / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D006959:Hyperoxaluria / Q000517:prevention & control*; D006960:Hyperoxaluria, Primary / Q000097:blood / Q000628:therapy* / Q000652:urine; D007669:Kidney Calculi / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D010070:Oxalates / Q000097:blood* / Q000652:urine*; D020624:Oxalobacter formigenes; D011379:Prognosis
chemical_list: D010070:Oxalates; D003404:Creatinine