Ali Hatem, Mohiuddin Atif, Sharma Ajay, Shaheen Ihab, Kim Jon Jin, El Kosi Mohsen, Halawa Ahmed
Department of Renal Medicine, Royal Stoke University Hospital, NHS Foundation Trust, Stoke-on-Trent, UK.
Institute of Medical Sciences, Faculty of Medicine, University of Liverpool, Liverpool, UK.
Clin Kidney J. 2019 Jan 14;12(4):592-599. doi: 10.1093/ckj/sfy132. eCollection 2019 Aug.
Interleukin-2 (IL-2) antagonist has been used as an induction therapy in many centres in calcineurin inhibitor-sparing regimens. Tacrolimus has overwhelmingly replaced cyclosporine in the maintenance immunosuppressive protocols in many transplant centres. The aim of our study and meta-analysis is to explore the effect of IL-2 induction therapy on the rate of rejection and patient and graft survival in standard-risk renal transplant patients with tacrolimus-based maintenance immunotherapy. Secondary aims included assessment of the effect of IL-2 induction therapy on creatinine change and the risk of cytomegalovirus (CMV) infection.
We conducted a systematic review in different databases to identify studies and research work that assessed the effect of IL-2 antibody induction therapy on renal transplant outcomes. Inclusion criteria for our meta-analysis were all studies that compared IL-2 induction therapy with placebo or no induction therapy in standard-risk renal transplant recipients on tacrolimus-based maintenance immunosuppressive therapy. Data collected were the name of the first author, journal title, year of publication, country where the study was conducted, number of patients in the IL-2 induction therapy arm and in the placebo arm, number of patients who had biopsy-proven rejection and graft survival in each arm. A random effects model was used for the meta-analysis.
Of the 470 articles found in different databases, 7 were included in the meta-analysis. Forest plot analysis for rate of rejection during the follow-up period post-transplant showed no significant difference between the groups. There was no evidence of heterogenicity between included studies ( = 21.8%, P = 0.27). The overall risk difference was -0.02 [95% confidence interval (CI) -0.05-0.01]. A random effects meta-analysis for patient and graft survival was performed using forest plot analysis and showed no significant effect of IL-2 receptor (IL-2R) antibody induction on patient or graft survival compared with placebo. The overall risk difference was -0.01 (95% CI -0.04-0.01) and 0.00 (95% CI -0.00-0.01), respectively. Three of the included studies showed no effect of basiliximab on creatinine change, two showed no effect on risk of CMV infection and two showed less risk of post-transplant diabetes in the basiliximab group.
IL-2R antibody induction therapy has no significant effect on the rate of rejection or patient or graft survival in standard-risk renal transplant recipients on tacrolimus-based maintenance immunotherapy. More randomized controlled studies are needed.
白细胞介素-2(IL-2)拮抗剂已在许多中心被用作钙调神经磷酸酶抑制剂无激素方案中的诱导治疗药物。在许多移植中心的维持免疫抑制方案中,他克莫司已压倒性地取代了环孢素。我们这项研究及荟萃分析的目的是探讨IL-2诱导治疗对接受基于他克莫司的维持免疫治疗的低危肾移植患者的排斥反应发生率、患者及移植物存活率的影响。次要目的包括评估IL-2诱导治疗对肌酐变化及巨细胞病毒(CMV)感染风险的影响。
我们在不同数据库中进行了系统综述,以识别评估IL-2抗体诱导治疗对肾移植结局影响的研究及科研工作。我们荟萃分析的纳入标准为所有在接受基于他克莫司的维持免疫抑制治疗的低危肾移植受者中,比较IL-2诱导治疗与安慰剂或无诱导治疗的研究。收集的数据包括第一作者姓名、期刊名称、发表年份、研究开展的国家、IL-2诱导治疗组和安慰剂组的患者数量、每组中经活检证实发生排斥反应的患者数量及移植物存活率。荟萃分析采用随机效应模型。
在不同数据库中检索到的470篇文章中,7篇被纳入荟萃分析。移植后随访期内排斥反应发生率的森林图分析显示,两组间无显著差异。纳入研究之间没有异质性证据(I² = 21.8%,P = 0.27)。总体风险差异为-0.02[95%置信区间(CI)-0.05 - 0.01]。使用森林图分析对患者及移植物存活率进行随机效应荟萃分析,结果显示与安慰剂相比,IL-2受体(IL-2R)抗体诱导对患者或移植物存活率无显著影响。总体风险差异分别为-0.01(95%CI -0.04 - 0.01)和0.00(95%CI -0.OO - 0.01)。纳入研究中的三项显示巴利昔单抗对肌酐变化无影响,两项显示对CMV感染风险无影响,两项显示巴利昔单抗组移植后糖尿病风险较低。
对于接受基于他克莫司的维持免疫治疗的低危肾移植受者,IL-2R抗体诱导治疗对排斥反应发生率、患者或移植物存活率均无显著影响。需要更多的随机对照研究。