Oxalobacter formigenes: a potential tool for the treatment of primary hyperoxaluria type 1
Oxalobacter formigenes: a potential tool for the treatment of primary hyperoxaluria type 1
复制标题
DOI：
10.1038/sj.ki.5001707
复制
发表时间：
2006-10-01
影响因子：
19.6
通讯作者：
Sidhu, H.
中科院分区：
文献类型：
--
作者：
Hoppe, B.;Beck, B.;Sidhu, H.
原发性高草酸尿症的特征是严重的尿石症、肾钙质沉着症和早期肾功能衰竭。由于治疗选择稀缺，我们的目标是寻找一种新的治疗工具，利用产草酸杆菌在结肠中降解内源性草酸盐。以冷冻糊剂(IxOC-2)或肠溶胶囊(IxOC-3)的形式口服草酸杆菌4周。 9 名患者（5 名肾功能正常，1 名肝肾移植后患者，3 名肾功能衰竭患者）完成了 IxOC-2 研究。 7 名患者（6 名肾功能正常，1 名肝肾移植后）完成了 IxOC-3 研究。在基线、治疗期间每周以及两周的随访中测定肾衰竭患者的尿草酸盐或血浆草酸盐。在第 3 周和第 4 周结束时均显示出 > 20% 减少的患者被视为有反应者。在 IxOC-2 下，五分之三肾功能正常的患者显示尿草酸减少了 22-48%。此外，两名肾衰竭患者的血浆草酸盐显着降低，临床症状得到改善。在 IxOC-3 治疗下，六分之四肾功能正常的患者的尿草酸盐减少了 38.5% 至 92%。尽管IxOC-2下的所有受试者和IxOC-3下的4名患者在治疗期间粪便中均显示出可检测到的O. formigenes水平，但粪便回收率在随访时直接下降，表明仅存在短暂的胃肠道定植。初步数据表明，O. formigenes 是安全的，可显着降低尿液或血浆草酸盐，并且是原发性高草酸尿症的潜在新治疗选择。
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.