Duineveld Caroline, Bouwmeester Romy N, Wijnsma Kioa L, Bemelman F J, van der Heijden J W, Berger S P, van den Heuvel L P W J, van de Kar Nicole C A J, Wetzels Jack F M
Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Nephrology, Nijmegen, The Netherlands.
Department of Pediatric Nephrology, Radboud University Medical Center, Amalia Children's Hospital, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
Kidney Int Rep. 2023 Jan 19;8(4):715-726. doi: 10.1016/j.ekir.2023.01.016. eCollection 2023 Apr.
Since 2016, kidney transplantation in patients with atypical hemolytic uremic syndrome (aHUS) in the Netherlands is performed without eculizumab prophylaxis. Eculizumab is given in case of posttransplant aHUS recurrence. Eculizumab therapy is monitored in the CUREiHUS study.
All participating kidney transplant patients who received eculizumab therapy for a suspected posttransplant aHUS recurrence were evaluated. Overall recurrence rate was monitored prospectively at Radboud University Medical Center.
In the period from January 2016 until October 2020, we included 15 (12 females, 3 males; median age 42 years, range 24-66 years) patients with suspected aHUS recurrence after kidney transplantation in this study. The time interval to recurrence showed a bimodal distribution. Seven patients presented early after transplantation (median 3 months, range 0.3-8.8 months), with typical aHUS features: rapid loss of estimated glomerular filtration rate (eGFR) and laboratory signs of thrombotic microangiopathy (TMA). Eight patients presented late (median 46 months, range 18-69 months) after transplantation. Of these, only 3 patients had systemic TMA, whereas 5 patients presented with slowly deteriorating eGFR without systemic TMA. Treatment with eculizumab resulted in improvement or stabilization of eGFR in 14 patients. Eculizumab discontinuation was tried in 7 patients; however, it was successful only in 3. At the end of the follow-up (median 29 months, range 3-54 months after start of eculizumab), 6 patients had eGFR <30 ml/min per 1.73 m. Graft loss had occurred in 3 of them. Overall, aHUS recurrence rate without eculizumab prophylaxis was 23%.
Rescue treatment of posttransplant aHUS recurrence is effective; however, some patients suffer from irreversible loss of kidney function, likely caused by delayed diagnosis and treatment and/or too aggressive discontinuation of eculizumab. Physicians should be aware that recurrence of aHUS can present without evidence of systemic TMA.
自2016年以来，荷兰非典型溶血性尿毒症综合征（aHUS）患者在肾移植时未接受依库珠单抗预防治疗。移植后aHUS复发时给予依库珠单抗治疗。依库珠单抗治疗在CUREiHUS研究中受到监测。
对所有因疑似移植后aHUS复发而接受依库珠单抗治疗的参与肾移植患者进行评估。在拉德堡德大学医学中心前瞻性监测总体复发率。
在2016年1月至2020年10月期间，本研究纳入了15例（12例女性，3例男性；中位年龄42岁，范围24 - 66岁）肾移植后疑似aHUS复发的患者。复发的时间间隔呈双峰分布。7例患者在移植后早期出现（中位时间3个月，范围0.3 - 8.8个月），具有典型的aHUS特征：估计肾小球滤过率（eGFR）迅速下降以及血栓性微血管病（TMA）的实验室指标异常。8例患者在移植后晚期出现（中位时间46个月，范围18 - 69个月）。其中，只有3例患者出现全身性TMA，而5例患者表现为eGFR缓慢下降且无全身性TMA。依库珠单抗治疗使14例患者的eGFR得到改善或稳定。7例患者尝试停用依库珠单抗；然而，仅3例成功。在随访结束时（依库珠单抗开始治疗后中位时间29个月，范围3 - 54个月），6例患者的eGFR <30 ml/min per 1.73 m²。其中3例发生了移植肾丢失。总体而言，未进行依库珠单抗预防治疗时aHUS的复发率为23%。
移植后aHUS复发的挽救治疗是有效的；然而，一些患者出现了不可逆的肾功能丧失，可能是由于诊断和治疗延迟以及/或过于激进地停用依库珠单抗所致。医生应意识到aHUS复发可能在没有全身性TMA证据的情况下出现。
