Division of Nephrology, Departments of Pediatrics and Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Division of Pediatric Nephrology, University Children's Hospital, Bonn, Germany.
Urolithiasis. 2018 Aug;46(4):313-323. doi: 10.1007/s00240-017-0998-6. Epub 2017 Jul 17.
Primary hyperoxaluria (PH) patients overproduce oxalate because of rare genetic errors in glyoxylate metabolism. Recurrent urolithiasis and/or progressive nephrocalcinosis are PH hallmarks and can lead to kidney damage, systemic oxalosis and death. Based on previous studies, we hypothesised that treatment with the oxalate-metabolizing bacterium Oxalobacter formigenes would mediate active elimination of oxalate from the plasma to the intestine of PH patients, thereby reducing urinary oxalate excretion (Uox). The efficacy and safety of O. formigenes (Oxabact™ OC3) were evaluated for 24 weeks in a randomised, placebo-controlled, double-blind study. The primary endpoint was reduction in Uox. Secondary endpoints included change in plasma oxalate (Pox) concentration, frequency of stone events, number of responders, and Uox in several subgroups. Additional post hoc analyses were conducted. Thirty-six patients were randomised; two patients withdrew from placebo treatment. Both OC3 and placebo groups demonstrated a decrease in Uox/urinary creatinine ratio, but the difference was not statistically significant. No differences were observed with respect to change in Pox concentration, stone events, responders' number or safety measures. In patients with estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m, Pox increased by 3.25 µmol/L in the placebo group and decreased by -1.7 µmol/L in the OC3 group (p = 0.13). After 24 weeks, eGFR had declined to a greater degree in the placebo than in the OC3 group: -8.00 ± 2.16 versus -2.71 ± 2.50; p = 0.01. OC3 treatment did not reduce urinary oxalate over 24 weeks of treatment compared with placebo in patients with PH. The treatment was well tolerated.
原发性高草酸尿症（PH）患者由于乙醛酸代谢中罕见的遗传错误而过度产生草酸。复发性尿路结石和/或进行性肾钙质沉着症是 PH 的标志，并可导致肾脏损伤、全身性草酸过多和死亡。基于先前的研究，我们假设用草酸代谢细菌 Oxalobacter formigenes 治疗将介导从血浆主动消除草酸到 PH 患者的肠道，从而减少尿草酸排泄（Uox）。在一项随机、安慰剂对照、双盲研究中，评估了 Oxalobacter formigenes（Oxabact™ OC3）治疗 24 周的疗效和安全性。主要终点是降低 Uox。次要终点包括血浆草酸（Pox）浓度的变化、结石事件的频率、应答者的数量以及几个亚组的 Uox。进行了额外的事后分析。36 名患者被随机分组；2 名患者退出安慰剂治疗。OC3 组和安慰剂组的 Uox/尿肌酐比值均降低，但差异无统计学意义。在 Pox 浓度、结石事件、应答者数量或安全性措施方面没有观察到差异。在估计肾小球滤过率（eGFR）<90 mL/min/1.73 m 的患者中，安慰剂组的 Pox 增加 3.25 µmol/L，而 OC3 组的 Pox 降低 -1.7 µmol/L（p = 0.13）。24 周后，安慰剂组的 eGFR 下降程度大于 OC3 组：-8.00 ± 2.16 与-2.71 ± 2.50；p = 0.01。与安慰剂相比，OC3 治疗在 24 周的治疗中并未降低 PH 患者的尿草酸。治疗耐受性良好。
