Sureshkumar Kalathil K, Chopra Bhavna
Division of Nephrology and Hypertension, Medicine Institute, Allegheny General Hospital, Allegheny Health Network, Pittsburgh, PA.
Division of Nephrology and Hypertension, Medicine Institute, Allegheny General Hospital, Allegheny Health Network, Pittsburgh, PA.
Transplant Proc. 2019 Jul-Aug;51(6):1796-1800. doi: 10.1016/j.transproceed.2019.04.059.
In kidney transplantation, donor recipient human leukocyte antigen (HLA)-DR mismatch signals high immunologic risk and portends inferior outcomes. We compared the impacts of depleting vs non-depleting antibody induction on the outcomes in kidney transplant recipients (KTRs) at different levels of HLA-DR mismatches.
Using the Organ Procurement and Transplantation Network/United Network for Organ Sharing database, we identified adult KTRs from 2001 to 2015 who received induction therapy with either depleting (thymoglobulin/alemtuzumab) or non-depleting (basiliximab/daclizumab) antibody and were discharged on calcineurin inhibitor/mycophenolic acid maintenance. Patients were then stratified by the number of donor-recipient HLA-DR mismatches (0, 1, 2) in both living donor (LD) and deceased donor (DD) KTRs. Under each HLA-DR mismatch category, long-term outcomes were compared for depleting vs non-depleting induction using a Cox model.
A total of 63,821 LD (HLA-DR mismatches: 0, n = 6945 [depleting = 4409, non-depleting = 2536]; 1, n = 19,557 [depleting = 13,558, non-depleting = 6019]; and 2, n = 10,727 [depleting = 7694, non-depleting = 3033]) and 64,922 DD (HLA-DR mismatches: 0, n = 13,915 [depleting = 10,124, non-depleting = 3791]; 1, n = 27,994 [depleting = 20,454, non-depleting = 7540]; and 2, n = 23,013 [depleting = 16,908, non-depleting = 6105]) KTRs were included in the analysis. Adjusted patient death risk was significantly lower in the depleting vs non-depleting antibody induction group among DD kidney recipients (hazard ratio 0.90, 95% CI 0.85-0.96, P = .001) and trended lower among LD kidney recipients (HR 0.88, 95% 0.79-1.01, P = .05) with 2 HLA-DR mismatches.
Our study found a patient survival benefit associated with the use of perioperative induction with depleting when compared to non-depleting antibody in KTRs with 2 HLA-DR mismatches and maintained on a calcineurin inhibitor/mycophenolic acid regimen.
在肾移植中，供受者人类白细胞抗原（HLA）-DR错配预示着高免疫风险和较差的预后。我们比较了在不同HLA-DR错配水平下，清除性抗体诱导与非清除性抗体诱导对肾移植受者（KTRs）预后的影响。
利用器官获取与移植网络/器官共享联合网络数据库，我们确定了2001年至2015年接受清除性（抗胸腺细胞球蛋白/阿仑单抗）或非清除性（巴利昔单抗/达利珠单抗）抗体诱导治疗并在出院时接受钙调神经磷酸酶抑制剂/霉酚酸维持治疗的成年KTRs。然后，根据活体供者（LD）和尸体供者（DD）KTRs中供受者HLA-DR错配的数量（0、1、2）对患者进行分层。在每个HLA-DR错配类别下，使用Cox模型比较清除性诱导与非清除性诱导的长期预后。
共有63821例LD（HLA-DR错配：0，n = 6945 [清除性 = 4409，非清除性 = 2536]；1，n = 19557 [清除性 = 13558，非清除性 = 6019]；2，n = 10727 [清除性 = 7694，非清除性 = 3033]）和64922例DD（HLA-DR错配：0，n = 13915 [清除性 = 10124，非清除性 = 3791]；1，n = 27994 [清除性 = 20454，非清除性 = 7540]；2，n = 23013 [清除性 = 16908，非清除性 = 6105]）KTRs纳入分析。在DD肾移植受者中，清除性抗体诱导组的调整后患者死亡风险显著低于非清除性抗体诱导组（风险比0.90，95%CI 0.85-0.96，P = 0.001），在有2个HLA-DR错配的LD肾移植受者中也有降低趋势（HR 0.88，95% 0.79-1.01，P = 0.05）。
我们的研究发现，与非清除性抗体相比，在有2个HLA-DR错配且接受钙调神经磷酸酶抑制剂/霉酚酸方案维持治疗的KTRs中，围手术期使用清除性抗体诱导可带来患者生存获益。
