Marcella-Neto Rubens, de Sá João R, Melaragno Cláudio S, Gonzalez Adriano M, Salzedas-Neto Alcides, Linhares Marcelo M, Medina-Pestana José O, Rangel Érika B
Nephrology Division, Federal University of São Paulo/Hospital do Rim e Hipertensão, São Paulo, SP, Brazil.
Endocrinology Division, Federal University of São Paulo, São Paulo, SP, Brazil.
Transplant Proc. 2020 Jun;52(5):1376-1379. doi: 10.1016/j.transproceed.2020.02.028. Epub 2020 Mar 22.
Pancreas transplant is an effective treatment for insulin-dependent diabetic individuals with end-stage renal disease, yet immunosuppression-associated adverse events may adversely affect patient and graft survival. The aim of the study was to document whether mammalian target of rapamycin inhibitors (mTORi) are safe and effective as a second-line drug after pancreas transplant.
An observational single-center study was performed in a cohort of 490 simultaneous pancreas-kidney transplant and 45 pancreas-after-kidney transplant individuals after conversion to mTORi (n = 13) owing to adverse events of either tacrolimus or mycophenolate.
mTORi conversion was performed 11.5 ± 10.1 (range, 1-28) months after pancreas transplant, mainly owing to cytomegalovirus infection and gastrointestinal intolerance. We frequently observed clinical complications after mTORi conversion, yet creatinine, eGFR, proteinuria, fasting plasma glucose, HbA1c, and C-peptide remained stable throughout the study (mean follow-up 8.2 ± 5, range 1-17) years, as did the lipid profile (P > .05). However, graft loss occurred in almost 20% of patients owing to chronic alterations.
The small number of patients and a single-center cohort were limitations of the study.
Late mTORi conversion is a safe and effective approach when tacrolimus or mycophenolate-mediated adverse events occur after pancreas transplant.
胰腺移植是终末期肾病胰岛素依赖型糖尿病患者的有效治疗方法，但免疫抑制相关不良事件可能对患者和移植物存活产生不利影响。本研究的目的是记录雷帕霉素靶蛋白抑制剂（mTORi）作为胰腺移植后二线药物是否安全有效。
对490例胰肾联合移植患者和45例肾移植后胰腺移植患者进行了一项观察性单中心研究，这些患者因他克莫司或霉酚酸酯的不良事件而转换为mTORi（n = 13）。
胰腺移植后11.5±10.1（范围1 - 28）个月进行mTORi转换，主要原因是巨细胞病毒感染和胃肠道不耐受。我们在mTORi转换后经常观察到临床并发症，但在整个研究期间（平均随访8.2±5，范围1 - 17年），肌酐、估算肾小球滤过率、蛋白尿、空腹血糖、糖化血红蛋白和C肽以及血脂谱均保持稳定（P>.05）。然而，由于慢性改变，近20%的患者发生了移植物丢失。
患者数量少和单中心队列是本研究的局限性。
当胰腺移植后发生他克莫司或霉酚酸酯介导的不良事件时，晚期mTORi转换是一种安全有效的方法。
