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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Effects of Conversion From Calcineurin Inhibitors to Sirolimus or Everolimus on Renal Function and Possible Mechanisms in Liver Transplant Recipients
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Effects of Conversion From Calcineurin Inhibitors to Sirolimus or Everolimus on Renal Function and Possible Mechanisms in Liver Transplant Recipients

机译：转化从钙素抑制剂转化对西罗莫司或everolimus对肝移植受者的肾功能和可能机制的影响

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Abstract Mammalian targets of rapamycin inhibitors (mTORIs), including sirolimus and everolimus, are used for minimizing calcineurin inhibitors after liver transplantation. However, head‐to‐head randomized comparisons of these 2 mTORIs are lacking. We assessed the differences in renoprotection and possible mechanisms between sirolimus and everolimus in liver transplant recipients. For this prospective cohort study, we recruited liver transplant recipients whose regimens were switched from tacrolimus to sirolimus or everolimus at a Taiwan medical center. Serial changes in estimated glomerular filtration rate (eGFR), urinary N‐acetyl‐β‐D‐glucosaminidase, neutrophil gelatinase–associated lipocalin, 8‐hydroxy‐2′‐deoxyguanosine, and transforming growth factor‐β1 during 1 year after mTORI conversion were compared within and between groups. In the 61 patients analyzed, no significant change in eGFR occurred within 12 months after conversion in both mTORI groups. Among patients with baseline eGFR 60 mL/min/1.73 m 2 , eGFR improved at 6 months and 1 year after conversion (+12.3 and +12.0 mL/min/1.73 m 2 , both P .05). Urinary N‐acetyl‐β‐D‐glucosaminidase decreased in both sirolimus and everolimus groups at 6 months (–68.7 ± 137.6 and –62.0 ± 92.4 U/g creatinine, both P .05), and the reduction of urinary neutrophil gelatinase–associated lipocalin was significant in the sirolimus group (–4345.1 ± 7763.5 ng/g creatinine; P .05). Neither transforming growth factor‐β1 nor 8‐hydroxy‐2′‐deoxyguanosine changed significantly. In conclusion, the renoprotective effect of mTORI conversion was significant in liver transplant recipients with renal insufficiency, which was similar for sirolimus and everolimus, in the first year and may be associated with ameliorated tubular injury. Available evidence remains insufficient to determine which mTORI conversion therapy is more effective in renoprotection in the long run.
机译：摘要哺乳动物的雷马霉素抑制剂（MTORIS）的靶标，包括西罗莫司和everolimus，用于最小化肝移植后的钙素蛋白抑制剂。然而，缺乏这两个mtoris的头部到头随机比较。我们评估了肝脏移植受者在西罗莫司和everolimus之间的阅潜水动膜和可能机制的差异。对于这项未来的队列研究，我们招募了肝移植受者，其方案从他克莫司切换到台湾医疗中心的西罗莫司或埃默里司。估计肾小球过滤速率（EGFR），尿N-乙酰-β-D-葡糖胺酶，中性粒细胞明胶酶相关脂素，8-羟基-2'-脱氧核苷酸和在MTORI转化后1年内转化生长因子-β1的序列变化在组内和之间比较。在61例患者中，在MTORI组转化后12个月内未发生重大变化。在基线EGFR患者中，60ml / min / 1.73 m 2，转化后6个月和1年改善（+12.3和+ 12.0ml / min / 1.73m 2，均为p <.05）。尿N-乙酰-β-D-葡糖胺酶在6个月（-68.7±137.6和-62.0±92.4u / g肌酐，尿液中噬菌体明胶酶的减少，在6个月内降低 - 分配的脂质甘油在西罗莫司基团中是显着的（-4345.1±7763.5ng / g肌酐; p <.05）。转化生长因子-β1也不是8-羟基-2'-脱氧核苷酸发生显着变化。总之，MTORI转化的重新保护作用在肝脏移植受者中具有肾功能不全的显着影响，其在第一年的西罗莫司和everolimus类似，并且可能与改善的管状损伤有关。可用证据仍然不足以确定哪种MTORI转化疗法在长期的RenoPotect中更有效。

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