Department of Pediatric Gastroenterology Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Pediatr Transplant. 2023 Jun;27(4):e14509. doi: 10.1111/petr.14509. Epub 2023 Mar 15.
Tacrolimus (TAC)-mediated renal disease occurs in up to 70% of pediatric liver transplant (LT) recipients. The safety and efficacy of renal-sparing immunosuppression using anti-thymocyte globulin (ATG) induction and delayed TAC administration has not been studied in children. We evaluated the safety and efficacy of ATG induction on preserving renal function in children within the first year (Y1) post-LT in a single-center retrospective cohort study.
Children under age 18 years of who received isolated LT from 2008 to 2020 with a GFR < 70 received renal-sparing (RS) protocol consisting of ATG with methylprednisolone (MP), delayed TAC administration, lower initial TAC trough goals, and mycophenolate mofetil (MMF). The RS group was matched 1:2 by age and LT indication with standard immunosuppression (SI) group. Changes in renal function as well as adverse events within Y1 post-LT were compared.
Forty-four pediatric patients were included in the analysis, of which 13 received RS. As expected, the RS group had significantly lower mean TAC trough levels at 30 days (10.3 vs. 13.2, p = .001) post-LT. Renal function was significantly preserved at 6 (-0.26 vs. 0.21, p = .004) and 12 months (-0.33 vs. 0.11, p = .003) post-LT in the RS versus SI group as measured by mean change in serum creatinine, with similar trends observed in eGFR and cystatin C. ACR, sepsis, viremia, graft loss and mortality occurred at similar rates in both RS and SI groups.
Induction immunosuppression with ATG and delayed TAC administration in children with renal impairment is safe and effectively preserves renal function during Y1 post-LT.
他克莫司(TAC)介导的肾病在高达 70%的儿科肝移植(LT)受者中发生。在儿童中,使用抗胸腺细胞球蛋白(ATG)诱导和延迟 TAC 给药的肾保护免疫抑制的安全性和有效性尚未得到研究。我们在一项单中心回顾性队列研究中评估了在 LT 后 1 年内(Y1)使用 ATG 诱导对儿童肾功能保护的安全性和有效性。
2008 年至 2020 年期间,年龄在 18 岁以下且 GFR<70 的孤立性 LT 受者接受了肾保护(RS)方案,包括 ATG 联合甲泼尼龙(MP)、延迟 TAC 给药、较低的初始 TAC 谷值目标和霉酚酸酯(MMF)。RS 组与标准免疫抑制(SI)组按年龄和 LT 适应证 1:2 匹配。比较 LT 后 Y1 内肾功能变化和不良事件。
44 例儿科患者纳入分析,其中 13 例接受 RS。如预期的那样,RS 组 LT 后 30 天(10.3 对 13.2,p=0.001)的平均 TAC 谷值水平显著降低。RS 组与 SI 组相比,在 LT 后 6 个月(-0.26 对 0.21,p=0.004)和 12 个月(-0.33 对 0.11,p=0.003)时血清肌酐的平均变化衡量的肾功能明显得到了保留,在 eGFR 和胱抑素 C 中也观察到了相似的趋势。RS 和 SI 组的 ACR、脓毒症、病毒血症、移植物丢失和死亡率相似。
在有肾功能损害的儿童中,使用 ATG 诱导免疫抑制和延迟 TAC 给药是安全的,可有效在 LT 后 Y1 内保留肾功能。