Efficacy and safety of Oxalobacter formigenes to reduce urinary oxalate in primary hyperoxaluria
Efficacy and safety of Oxalobacter formigenes to reduce urinary oxalate in primary hyperoxaluria
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DOI：
10.1093/ndt/gfr107
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发表时间：
2011-11-01
影响因子：
6.1
通讯作者：
Milliner, Dawn
中科院分区：
文献类型：
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作者：
Hoppe, Bernd;Groothoff, Jaap W.;Milliner, Dawn
背景原发性高草酸尿症（PH）是一种罕见的遗传性疾病，其中高尿草酸盐（Uox）引起复发性肾结石和/或进行性肾钙质沉着，通常随后是早期终末期肾病，以及极高的血浆草酸盐、全身性草酸盐沉着和过早死亡。产草酸杆菌是一种厌氧草酸盐降解菌，在大多数人的结肠中自然定植。口服O.发现甲酸根（Oxabact）显著减少尿和血浆草酸盐。本研究采用随机、双盲、安慰剂对照的多中心临床研究，评价其疗效和安全性。在全球9个PH转诊中心，PH患者（> 5岁，Uox > 1.0 mmol/1.73 m2/d，肾小球滤过率（GFR）> 50 mL/min）接受口服Oxabact。主要终点是治疗24周后Uox（mmol/1.73m2/d）较基线的变化（降低> 20%）。在43例随机化受试者中，42例患者接受安慰剂（23例受试者）或Oxabact（19例受试者）。Uox的变化< 20%，组间无差异（P = 0.616）。对37例依从药物和尿液处理的患者进行了专门分析。在接受Oxabact的受试者中，Uox的变化为-19%，安慰剂组为-10%，P = 0.288），但Uox的变化为-21%和-7%，Uox表示为摩尔肌酐比（Ox：Cr，mmol/mol，P = 0.06）。对于基线值较高的患者，Ox：Cr降低更明显（> 160 mmol/mol，Oxabact-28%，安慰剂-6%; P < 0.082）。未发现严重不良事件。Oxabact安全且耐受性良好。然而，由于未观察到Uox的显著变化，因此需要进一步研究来评价Oxabact治疗的疗效。
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/1.73m(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/1.73m(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.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.