Department of Nephrology, Kidney Transplantation and Hemodialysis, Rouen University Hospital, Rouen, France.
Nephrology and Transplantation Department, Cancerology-Immunity-Transplantation-Infectiology, Clinical Investigation Center-Biotherapies, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, INSERM U955, Paris-Est-Créteil University, Paris, France.
Nephrol Dial Transplant. 2023 Feb 13;38(2):481-490. doi: 10.1093/ndt/gfac178.
Immunosuppression in kidney transplant recipients with decreased graft function and histological vascular changes can be particularly challenging. The impact of a late rescue conversion to belatacept on kidney graft survival in this context has never been studied.
We report a bicentric retrospective cohort study comparing a calcineurin inhibitor (CNI) to belatacept switch versus CNI continuation in 139 kidney transplant recipients with histological kidney vascular damage (cv ≥2, g + cpt ≤1, i + t ≤1) and low estimated glomerular filtration rate (≤40 mL/min/1.73 m²). Primary outcome was death-censored graft survival.
During the study follow-up, 10 graft losses (14.5%) occurred in the belatacept group (n = 69) versus 26 (37.1%) in the matched CNI group (n = 70) (P = .005). Death-censored graft survival was significantly higher in the belatacept group (P = .001). At 3 years, graft survival was 84.0% in the belatacept group compared with 65.1% in the control group. Continuing CNI was an independent risk factor for graft loss [hazard ratio (HR) 3.46; P < .005]. The incidence of cellular rejection after the conversion was low (4.3% in both groups) and not significantly different between groups (P = .84). Patients switched to belatacept developed significantly less donor-specific antibodies de novo. Belatacept was an independent risk factor for the occurrence of opportunistic infections (HR 4.84; P < .005).
The replacement of CNI with belatacept in patients with decreased allograft function and vascular lesions is associated with an improvement in graft survival and represents a valuable option in a context of organ shortage. Caution should be exercised regarding the increased risk of opportunistic infection.
对于移植肾功能下降和组织学血管改变的肾移植受者,免疫抑制治疗可能具有挑战性。在这种情况下,晚期改用贝利尤单抗对移植肾存活的影响尚未被研究过。
我们报告了一项双中心回顾性队列研究,比较了在 139 例存在组织学肾脏血管损伤(cv≥2、g+cpt≤1、i+t≤1)和估算肾小球滤过率低(≤40ml/min/1.73m²)的肾移植受者中,由钙调磷酸酶抑制剂(CNI)转换为贝利尤单抗或继续使用 CNI 的疗效。主要结局是经死亡校正的移植物存活率。
在研究随访期间,贝利尤单抗组(n=69)中有 10 例移植物丢失(14.5%),而匹配的 CNI 组(n=70)中有 26 例(37.1%)(P=0.005)。贝利尤单抗组的经死亡校正的移植物存活率显著更高(P=0.001)。在 3 年时,贝利尤单抗组的移植物存活率为 84.0%,而对照组为 65.1%。继续使用 CNI 是移植物丢失的独立危险因素[风险比(HR)3.46;P<0.005]。转换后细胞性排斥反应的发生率较低(两组均为 4.3%),且两组间无显著差异(P=0.84)。转换为贝利尤单抗的患者明显较少出现新的供体特异性抗体。贝利尤单抗是发生机会性感染的独立危险因素(HR 4.84;P<0.005)。
在移植肾功能下降和血管病变的患者中,用贝利尤单抗替代 CNI 与移植物存活率的提高相关,在器官短缺的情况下是一种有价值的选择。应注意机会性感染风险增加的问题。