Kamar Nassim, Bertrand Dominique, Caillard Sophie, Pievani Danièle, Apithy Marie Joelle, Congy-Jolivet Nicolas, Chauveau Bertrand, Farce Fabienne, François Arnaud, Delas Audrey, Olagne Jérôme, Usureau Cédric, Taupin Jean-Luc, Guidicelli Gwenda Line, Couzi Lionel
Department of Nephrology and Organ Transplantation, Toulouse University Hospital, INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Université Paul Sabatier, Toulouse, France.
Department of Nephrology, Dialysis and Kidney Transplantation, CHU Rouen, Rouen, France.
Kidney Int Rep. 2024 Jul 30;9(10):2927-2936. doi: 10.1016/j.ekir.2024.07.024. eCollection 2024 Oct.
Imlifidase is authorized for desensitization of highly sensitized adult kidney transplant candidates with a positive crossmatch (XM) against a deceased donor. Here, we report on the results for the first 9 patients transplanted in this context who had at least 3 months of follow-up.
The eligibility criteria were as follows: calculated panel reactive antibodies (cPRA) ³ 98%, ³ 3 years on the waiting list, immunodominant donor-specific antibodies (DSAs) with mean fluorescence intensity (MFI) > 6000 (and < 5000 at 1:10 dilution) and a negative post-imlifidase complement-dependent cytotoxic XM (CDCXM).
All 9 patients had been on dialysis for an average of 123 ± 41 months, with cPRA at 99% ( = 2) or 100% ( = 7). At transplantation, the mean number of DSAs was 4.3 ± 1.4. The median immunodominant DSA MFI was 9153 (6430-16,980). Flow cytometry XM (FCXM) and CDCXM before imlifidase were positive in 9 and 2 patients, respectively. After 1 injection of imlifidase, all were negative. Patients received polyclonal antibodies, i.v. Igs (IVIg), rituximab, tacrolimus, and mycophenolate. Five patients had a DSA rebound within the first 14 days: 2 had concomitant clinical antibody-mediated rejection (ABMR), 2 had subclinical ABMR, and 1 had isolated positive C4d staining. No ABMR was observed in patients without rebound. Chronic Kidney Disease-Epidemiology Collaboration formula estimated glomerular filtration rate (eGFR) was 56 ± 22 ml/min per 1.73 m at the last follow-up (7 ± 2.8 months). No graft loss or death were observed. Four patients developed at least 1 infection.
These real-life data demonstrate that the use of imlifidase to desensitize highly sensitized patients can have an acceptable short-term efficacy and safety profile in selected patients.
伊姆利菲酶被批准用于对与已故供体交叉配型（XM）呈阳性的高度致敏成年肾移植候选者进行脱敏治疗。在此，我们报告在此背景下接受移植的首批9例患者至少3个月的随访结果。
入选标准如下：计算得出的群体反应性抗体（cPRA）≥98%，在等待名单上≥3年，免疫显性供体特异性抗体（DSA）的平均荧光强度（MFI）>6000（且在1:10稀释时<5000），以及伊姆利菲酶治疗后补体依赖细胞毒性交叉配型（CDCXM）呈阴性。
所有9例患者均已接受平均123±41个月的透析，cPRA为99%（n = 2）或100%（n = 7）。移植时，DSA的平均数量为4.3±1.4。免疫显性DSA的MFI中位数为9153（6430 - 16,980）。在使用伊姆利菲酶之前，流式细胞术交叉配型（FCXM）和CDCXM在9例和2例患者中分别呈阳性。注射1剂伊姆利菲酶后，所有结果均为阴性。患者接受了多克隆抗体、静脉注射免疫球蛋白（IVIg）、利妥昔单抗、他克莫司和霉酚酸酯。5例患者在最初14天内出现DSA反弹：2例伴有临床抗体介导的排斥反应（ABMR），2例伴有亚临床ABMR，1例仅C4d染色呈阳性。未出现反弹的患者未观察到ABMR。在最后一次随访（7±2.8个月）时，慢性肾脏病流行病学协作组公式估算的肾小球滤过率（eGFR）为56±22 ml/min/1.73 m²。未观察到移植物丢失或死亡。4例患者发生至少1次感染。
这些实际数据表明，在选定患者中使用伊姆利菲酶对高度致敏患者进行脱敏治疗可具有可接受的短期疗效和安全性。
