DataSheet_1_Conversion From Calcineurin Inhibitors to Mammalian Target of Rapamycin Inhibitors in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.docx

BackgroundA systematic review and meta-analysis were performed to investigate the efficacy and safety of conversion from calcineurin inhibitors (CNIs) to mammalian target of rapamycin inhibitors (mTORi) in kidney transplant recipients (KTRs).
MethodsMEDLINE, EMBASE, PubMed, and Cochrane Library were searched to identify randomized controlled trials (RCTs) that compared the continuation of CNI with conversion to mTORi therapy.
ResultsTwenty-nine RCTs (5,747 KTRs) were included in our analysis. Meta-analysis of the glomerular filtration rate (SMD 0.20; 95%CI 0.10–0.31; P<0.01) and malignancy (RR 0.74; 95%CI 0.55–0.99; P=0.04) demonstrated a significant advantage of mTORi conversion over CNI continuation. However, the risk of acute rejection (RR 1.58; 95%CI 1.22–2.04; P<0.01), infection (RR 1.55; 95%CI 1.01–1.31; P=0.04), proteinuria (RR 1.87; 95%CI 1.34–2.59; P<0.01), leukopenia (RR 1.56; 95%CI 1.27–1.91; P<0.01), acne (RR 6.43; 95%CI 3.43–12.04; P<0.01), and mouth ulcer (RR 11.70; 95%CI 6.18–22.17; P<0.01) were higher in the mTORi group. More patients in the conversion group had to discontinue study medication (RR 2.52; 95%CI 1.75–3.63; P<0.01). There was no significant difference between the two groups with regard to death, graft loss, diabetes, chronic allograft nephropathy, and interstitial fibrosis/tubular atrophy.
ConclusionsPosttransplant patients have a better graft function and lower incidence of malignancy after conversion from CNI to mTORi therapy. However, this conversion strategy may be prevented by the higher drug discontinuation rate due to mTORi-associated adverse events, such as more acute rejection, infection, proteinuria, leukopenia, acne, and mouth ulcer, indicating that conversion therapy may only be a treatment option in selected patients.

背景：本研究采用系统评价与Meta分析方法，旨在探讨肾移植受者（kidney transplant recipients, KTRs）将钙调磷酸酶抑制剂（calcineurin inhibitors, CNIs）转换为雷帕霉素靶蛋白抑制剂（mammalian target of rapamycin inhibitors, mTORi）治疗的有效性与安全性。
方法：检索MEDLINE、EMBASE、PubMed及Cochrane Library数据库，筛选对比持续使用CNI治疗与转换为mTORi治疗的随机对照试验（randomized controlled trials, RCTs）。
结果：本分析共纳入29项随机对照试验，涉及5747名肾移植受者。Meta分析结果显示，相较于持续使用CNI治疗，转换为mTORi治疗在肾小球滤过率（标准化均数差standardized mean difference, SMD=0.20；95%置信区间95% confidence interval, 95%CI=0.10~0.31；P<0.01）及恶性肿瘤发生率（相对危险度relative risk, RR=0.74；95%CI=0.55~0.99；P=0.04）方面具有显著优势。但mTORi组的急性排斥反应风险（RR=1.58；95%CI=1.22~2.04；P<0.01）、感染风险（RR=1.55；95%CI=1.01~1.31；P=0.04）、蛋白尿发生率（RR=1.87；95%CI=1.34~2.59；P<0.01）、白细胞减少症发生率（RR=1.56；95%CI=1.27~1.91；P<0.01）、痤疮发生率（RR=6.43；95%CI=3.43~12.04；P<0.01）及口腔溃疡发生率（RR=11.70；95%CI=6.18~22.17；P<0.01）均更高。转换组中需停用研究药物的患者比例显著更高（RR=2.52；95%CI=1.75~3.63；P<0.01）。两组在死亡率、移植物丢失、糖尿病、慢性移植肾肾病及间质纤维化/肾小管萎缩方面无显著差异。
结论：肾移植受者将CNI转换为mTORi治疗后，移植物功能更佳，恶性肿瘤发生率更低。但由于mTORi相关不良反应（如更高的急性排斥反应、感染、蛋白尿、白细胞减少症、痤疮及口腔溃疡发生率）导致药物停用率升高，该转换策略的临床应用可能受到限制，提示转换治疗仅可作为特定患者的可选治疗方案。