■血浆置换疗法(PEX)在依库珠单抗可用之前是血栓性微血管病的标准治疗方法,目前仍被广泛应用。然而,大多数PEX患者最终仍进展为终末期肾病(ESRD).已经提出,输注含有活性补体的血浆可以诱导额外的补体激活,随后激活嗜中性粒细胞和内皮细胞。导致器官损伤加重和肾功能恶化。
■这项观察性试点研究检查了血液透析的效果,依库珠单抗和PEX治疗前后aHUS患者血浆中的补体-,中性粒细胞和内皮细胞活化。
■11名患者被纳入本初步研究。6例患者接受血液透析治疗,2例患者接受定期输注依库珠单抗,3例患者定期接受PEX治疗。在3次连续治疗期间随访患者。在患者接受治疗之前和之后采集血液样本。
■PEX后患者血浆中补体激活产物增加,与接受血液透析或依库珠单抗治疗的患者相反。在用于PEX的全血浆中检测到补体活化产物水平增加。此外,在血液透析和PEX后观察到患者中性粒细胞和内皮细胞的活化,但不适用于接受依库珠单抗治疗的患者。
■在这项初步研究中,我们观察到PEX诱导补体和中性粒细胞活化,而无血浆中含有大量的补体激活产物。此外,我们证明血液透析诱导中性粒细胞和内皮细胞的活化。补体激活和随后的中性粒细胞激活可能导致器官功能的恶化,并可能导致ESRD。需要进一步的随机对照研究来研究PEX对血栓性微血管病变患者补体和中性粒细胞活化的影响。
UNASSIGNED: Plasma exchange therapy (PEX) was standard treatment for thrombotic microangiopathy before eculizumab was available and is still widely applied. However, most PEX patients still ultimately progress to end-stage renal disease (ESRD). It has been suggested that infusion of plasma that contains active complement may induce additional complement activation with subsequent activation of neutrophils and endothelial cells, leading to exacerbation of organ damage and deterioration of renal function.
UNASSIGNED: This observational pilot study examines the effect of hemodialysis, eculizumab and PEX before and after treatment in plasma of aHUS patients on complement-, neutrophil and endothelial cell activation.
UNASSIGNED: Eleven patients were included in this pilot study. Six patients were treated with hemodialysis, 2 patients received regular infusions of eculizumab, and 3 patients were on a regular schedule for PEX. Patients were followed during 3 consecutive treatments. Blood samples were taken before and after patients received their treatment.
UNASSIGNED: Complement activation products increased in plasma of patients after PEX, as opposed to patients treated with hemodialysis or eculizumab. Increased levels of complement activation products were detected in omniplasma used for PEX. Additionally, activation of neutrophils and endothelial cells was observed in patients after hemodialysis and PEX, but not in patients receiving eculizumab treatment.
UNASSIGNED: In this pilot study we observed that PEX induced complement and neutrophil activation, and that omniplasma contains significant amounts of complement activation products. Additionally, we demonstrate that hemodialysis induces activation of neutrophils and endothelial cells. Complement activation with subsequent neutrophil activation may contribute to the deterioration of organ function and may result in ESRD. Further randomized controlled studies are warranted to investigate the effect of PEX on complement- and neutrophil activation in patients with thrombotic microangiopathy.