Efficacy and safety of Oxalobacter formigenes to reduce urinary oxalate in primary hyperoxaluria

• Published in: Nephrology, dialysis, transplantation Vol. 26; no. 11; pp. 3609 - 3615
• Main Authors: Hoppe, Bernd, Groothoff, Jaap W., Hulton, Sally-Anne, Cochat, Pierre, Niaudet, Patrick, Kemper, Markus J., Deschênes, George, Unwin, Robert, Milliner, Dawn
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.2011
• Subjects: Administration, Oral; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Creatinine - urine; Double-Blind Method; Emergency and intensive care: renal failure. Dialysis management; Errors of metabolism; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hyperoxaluria - prevention & control; Hyperoxaluria, Primary - blood; Hyperoxaluria, Primary - therapy; Hyperoxaluria, Primary - urine; Intensive care medicine; Kidney Calculi - etiology; Kidney Calculi - metabolism; Kidney Calculi - prevention & control; Kidney Failure, Chronic - etiology; Kidney Failure, Chronic - metabolism; Kidney Failure, Chronic - prevention & control; Male; Medical sciences; Metabolic diseases; Miscellaneous hereditary metabolic disorders; Oxalates - blood; Oxalates - urine; Oxalobacter formigenes; Prognosis; treatment; primary hyperoxaluria; safety; efficacy; Kidney disease; Urinary system disease; Hemodialysis; Oxalate; Metabolic diseases; Enzymopathy; Genetic disease; Extrarenal dialysis; Treatment; Renal failure; Oxalobacter formigenes; Hyperoxaluria
• ISSN: 0931-0509; 1460-2385; 1460-2385
• DOI: 10.1093/ndt/gfr107

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/1.73m2/day, glomerular filtration rate (GFR) > 50 mL/min) at nine PH referral sites worldwide. Primary endpoint was the change from baseline in Uox (mmol/1.73m2/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. Conclusion. 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.