Oxalobacter formigenes: a potential tool for the treatment of primary hyperoxaluria type 1.
Primary hyperoxaluria is characterized by severe urolithiasis, nephrocalcinosis, and early renal failure. As treatment options are scarce, we aimed for a new therapeutic tool using colonic degradation of endogenous oxalate by Oxalobactor formigenes. Oxalobacter was orally administered for 4 weeks as frozen paste (IxOC-2) or as enteric-coated capsules (IxOC-3). Nine patients (five with normal renal function, one after liver-kidney transplantation, and three with renal failure) completed the IxOC-2 study. Seven patients (six with normal renal function and one after liver-kidney transplantation) completed the IxOC-3 study. Urinary oxalate or plasma oxalate in renal failure was determined at baseline, weekly during treatment and for a 2-week follow-up. The patients who showed >20% reduction both at the end of weeks 3 and 4 were considered as responders. Under IxOC-2, three out of five patients with normal renal function showed a 22-48% reduction of urinary oxalate. In addition, two renal failure patients experienced a significant reduction in plasma oxalate and amelioration of clinical symptoms. Under IxOC-3 treatment, four out of six patients with normal renal function responded with a reduction of urinary oxalate ranging from 38.5 to 92%. Although all subjects under IxOC-2 and 4 patients under IxOC-3 showed detectable levels of O. formigenes in stool during treatment, fecal recovery dropped directly at follow up, indicating only transient gastrointestinal-tract colonization. The preliminary data indicate that O. formigenes is safe, leads to a significant reduction of either urinary or plasma oxalate, and is a potential new treatment option for primary hyperoxaluria.
Hoppe
B
B
Division of Pediatric Nephrology, University Children's Hospital Cologne, Cologne, Germany. Bernd.Hoppe@uk-koeln.de
Beck
B
B
Gatter
N
N
von Unruh
G
G
Tischer
A
A
Hesse
A
A
Laube
N
N
Kaul
P
P
Sidhu
H
H
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002214:Capsules; D002648:Child; D002675:Child, Preschool; D002849:Chromatography, Gas; D003404:Creatinine / Q000652:urine; D005243:Feces / Q000382:microbiology; D005260:Female; D005410:Flame Ionization; D005500:Follow-Up Studies; D006801:Humans; D006960:Hyperoxaluria, Primary / Q000097:blood / Q000145:classification / Q000150:complications / Q000628:therapy* / Q000652:urine; D007668:Kidney / Q000502:physiology; D007674:Kidney Diseases / Q000150:complications / Q000000981:diagnostic imaging; D007676:Kidney Failure, Chronic / Q000150:complications; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010070:Oxalates / Q000097:blood / Q000652:urine; D020624:Oxalobacter formigenes / Q000302:isolation & purification; D013997:Time Factors; D016896:Treatment Outcome; D014463:Ultrasonography
D002214:Capsules; D010070:Oxalates; D003404:Creatinine