Department of Nephrology and Transplantation, Hôpital Necker-Enfants Malades, AP-HP, 149 rue de Sèvres, 75015 Paris, France.
Université Paris Descartes, Paris, France.
Nephrol Dial Transplant. 2016 Dec;31(12):2122-2130. doi: 10.1093/ndt/gfw314. Epub 2016 Sep 1.
A therapeutic strategy based on complement blockade by eculizumab is widely used to treat atypical haemolytic uraemic syndrome (aHUS). Recent data are available on the administration of eculizumab during pregnancy in patients treated for paroxysmal nocturnal haemoglobinuria but there are very few data for aHUS patients.
We analysed the use of eculizumab for the treatment of aHUS during five pregnancies in three patients and studied an additional pregnancy without eculizumab. Obstetrical data and maternal and foetal complications during pregnancy, at delivery, and during the post-partum period were recorded.
The mean age at pregnancy was 28.5 (range 25-33) years. The mean serum creatinine before pregnancy was 189 (range 130-300) µmol/L and the mean eGFR was 32 (range 18-45) mL/min/1.73 m. One patient who stopped eculizumab 3 weeks after conception had a termination due to a relapse of HUS at 12 weeks of gestation (WG) during a first pregnancy and an intrauterine death at 24 WG despite continuous eculizumab treatment during a second pregnancy. In the other four pregnancies, treatment stabilized clinical and laboratory markers until 29-34 WG, but did not prevent hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome in one patient or pre-eclampsia in two other patients. All babies were born preterm and two presented with growth retardation. The mean body weight was 1632.5 (range 1070-2500) g. The dose of eculizumab had to be increased during all pregnancies due to incomplete complement blockade.
Eculizumab therapy during pregnancy displayed no overt safety issues but did not appear to prevent HELLP syndrome or pre-eclampsia in these high-risk chronic kidney disease patients.
依库珠单抗的补体阻断疗法被广泛用于治疗非典型溶血尿毒综合征（aHUS）。目前已有关于阵发性夜间血红蛋白尿患者在妊娠期间使用依库珠单抗的数据，但关于 aHUS 患者的数据非常有限。
我们分析了 3 名患者在 5 次妊娠期间使用依库珠单抗治疗 aHUS 的情况，并研究了一次未使用依库珠单抗的妊娠。记录了妊娠期间、分娩时和产后期间的产科数据以及母婴并发症。
妊娠时的平均年龄为 28.5 岁（范围 25-33 岁）。妊娠前血清肌酐平均值为 189µmol/L（范围 130-300µmol/L），eGFR 平均值为 32mL/min/1.73m（范围 18-45mL/min/1.73m）。1 名患者在受孕后 3 周停止使用依库珠单抗，在首次妊娠 12 周时因 HUS 复发而终止妊娠，在第二次妊娠期间持续使用依库珠单抗治疗，但仍在 24 周时发生宫内死亡。在另外 4 次妊娠中，治疗稳定了临床和实验室标志物，直到 29-34 周，但未能预防其中 1 名患者的溶血性肝酶升高和血小板减少（HELLP）综合征或另外 2 名患者的子痫前期。所有婴儿均早产，2 名婴儿出现生长迟缓。平均体重为 1632.5g（范围 1070-2500g）。由于不完全的补体阻断，所有妊娠期间都需要增加依库珠单抗的剂量。
在妊娠期间使用依库珠单抗治疗未显示出明显的安全性问题，但似乎不能预防这些高危慢性肾脏病患者的 HELLP 综合征或子痫前期。
