Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, 1600 SW Archer Road, Medical Science Bldg, NG-4, Gainesville, FL, 32610, USA.
Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Int Urol Nephrol. 2019 Nov;51(11):2063-2072. doi: 10.1007/s11255-019-02251-w. Epub 2019 Aug 5.
In large observational studies of adult kidney transplant recipients (KTRs) where older adults (65 years old and older) were not well represented, the mammalian target of rapamycin inhibitors (mTOR inhibitors) has poorer outcomes than the standard tacrolimus-mycophenolate-steroids (TAC-MPA-S) regimen. We conducted this study to compare the outcomes of regimens containing the common mTOR inhibitor, sirolimus (SRL) against TAC-MPA-S in older adult KTRs.
Using the 2000-2016 Scientific Registry of Transplant Recipients, Cox multivariable regression models were conducted to analyze the patient and graft outcomes associated with regimens containing SRL, steroids (S) and cyclosporine (CSA), tacrolimus (TAC), or mycophenolate (MPA) vs. the standard (TAC-MPA-S) regimen in older adult KTRs.
Included in the analysis were 15,008 (95.19%) older adult KTRs on standard (TAC-MPA-S) regimen, 242 (1.53%) on SRL-MPA-S, 300 (1.90%) on SRL-TAC-S, and 217 (1.38%) on SRL-CSA-S. Compared with the standard regimen, the adjusted risks of all-cause death and overall graft loss over a maximum 5-year follow-up were highest with SRL-MPA-S, intermediate with SRL-TAC-S and not significantly different with SRL-CSA-S. The adjusted risks of all-cause death and overall graft loss were modified by a pre-transplant history of malignancy in older adult KTRs on SRL-TAC-S, not in those on SRL-MPA-S or SRL-CSA-S.
In older adult kidney transplant recipients, SRL-TAC-S or SRL-MPA-S, but not SRL-CSA-S is associated with higher risks of death and allograft loss than standard TAC-MPA-S regimen and a pre-transplant malignancy history worsens these risks in patients on SRL-TAC-S. Confirmation of our findings by a prospective randomized trial is needed before translation into clinical practice can be recommended.
在大型成人肾移植受者（KTR）观察性研究中，老年人（65 岁及以上）的代表性不足，哺乳动物雷帕霉素靶蛋白抑制剂（mTOR 抑制剂）的结果不如标准他克莫司-霉酚酸-皮质类固醇（TAC-MPA-类固醇）方案。我们进行这项研究是为了比较含有常见 mTOR 抑制剂西罗莫司（SRL）的方案与 TAC-MPA-S 在老年 KTR 中的结果。
利用 2000-2016 年移植受者科学注册处，采用 Cox 多变量回归模型分析了 SRL、类固醇（S）和环孢素（CSA）、他克莫司（TAC）或吗替麦考酚酯（MPA）与老年 KTR 标准（TAC-MPA-S）方案相关的患者和移植物结局。
纳入分析的有 15008 例（95.19%）接受标准（TAC-MPA-S）方案的老年 KTR、242 例（1.53%）接受 SRL-MPA-S 方案、300 例（1.90%）接受 SRL-TAC-S 方案和 217 例（1.38%）接受 SRL-CSA-S 方案。与标准方案相比，在最大 5 年随访期间，SRL-MPA-S 方案的全因死亡和整体移植物丢失的调整风险最高，SRL-TAC-S 方案的调整风险中等，SRL-CSA-S 方案的调整风险无显著差异。在 SRL-TAC-S 方案治疗的老年 KTR 中，移植前恶性肿瘤史改变了全因死亡和整体移植物丢失的调整风险，但在 SRL-MPA-S 或 SRL-CSA-S 方案中没有改变。
在老年肾移植受者中，SRL-TAC-S 或 SRL-MPA-S 方案而非 SRL-CSA-S 与标准 TAC-MPA-S 方案相比，死亡和移植物丢失的风险更高，而移植前恶性肿瘤史会增加 SRL-TAC-S 患者的这些风险。需要前瞻性随机试验来证实我们的发现，然后才能推荐将其转化为临床实践。
