Fatly Zainab Al, Betjes Michiel Gh, van Gestel Judith, Verschragen Marieken, de Weerd Annelies E
Department of Internal Medicine, Erasmus Medical Center Transplant Institute, University Medical Center Rotterdam, Rotterdam, Netherlands.
Front Nephrol. 2022 Jul 19;2:933954. doi: 10.3389/fneph.2022.933954. eCollection 2022.
Tacrolimus (TAC) combined with mycophenolate mofetil (MMF) is the immunosuppressive regimen in the majority of solid organ transplant recipients. Gastrointestinal complaints are frequent, which is considered predominantly a side effect of MMF. However, systematic research in this field is lacking. The aim of this study is to systematically investigate the burden of gastrointestinal complaints in TAC-treated kidney transplant recipients with and without MMF.
In a single-center, open-label, randomized controlled trial, low immunological risk recipients were randomized to either TAC and MMF or to TAC monotherapy from 6 months after kidney transplantation onwards [NTR4672],. They filled in the Gastrointestinal Symptom Rating Scale questionnaire, which covers five dimensions (abdominal pain, reflux, indigestion, constipation, and diarrhea), 6, 12, and 15 months after transplantation.
Seventy-nine recipients were randomized and 72 completed all questionnaires (34 TACmono and 38 TAC/MMF). At baseline, the mean age was 59 years with 72% male, mean BMI 28 kg/m, eGFR 55 ml/min/1.73m2, mean daily dose MMF 1200 mg and TAC 5.8 mg, with trough levels of 2.1 mg/L and 7.4 ug/L. Six months after transplantation, 75% of recipients reported troublesome symptoms (score ≥3). Diarrhea was the most troublesome (mean 3.3) and discontinuing MMF significantly reduced it (mean Δ score between month 6 and 15 TAC/MMF -0.9 vs. TACmono -1.8, p=0.03). In recipients with troublesome symptoms, abdominal pain (2.7 to 1.8, p=0.003), indigestion (2.8 to 2.3, p=0.012), and reflux (2.9 to 1.7, p=0.007) significantly decreased over time, independent of MMF use.
The majority of kidney transplant recipients with TAC and MMF experienced troublesome gastrointestinal symptoms 6 months after transplantation. While constipation remained troublesome, indigestion, abdominal pain, and reflux improved over time by month 15. Diarrhea only improved after discontinuing MMF.
他克莫司（TAC）联合霉酚酸酯（MMF）是大多数实体器官移植受者的免疫抑制方案。胃肠道不适很常见，这主要被认为是MMF的副作用。然而，该领域缺乏系统性研究。本研究的目的是系统调查接受TAC治疗的肾移植受者中，使用和未使用MMF时胃肠道不适的负担。
在一项单中心、开放标签、随机对照试验中，低免疫风险受者在肾移植后6个月起被随机分为接受TAC和MMF治疗组或TAC单药治疗组[NTR4672]。他们在移植后6个月、12个月和15个月填写胃肠道症状评分量表问卷，该问卷涵盖五个维度（腹痛、反流、消化不良、便秘和腹泻）。
79名受者被随机分组，72名完成了所有问卷（34名单用TAC和38名使用TAC/MMF）。基线时，平均年龄为59岁，男性占72%，平均体重指数28kg/m²，估算肾小球滤过率55ml/min/1.73m²，MMF平均日剂量1200mg，TAC平均日剂量5.8mg，谷浓度分别为2.1mg/L和7.4μg/L。移植后6个月，75%的受者报告有困扰症状（评分≥3）。腹泻是最困扰的症状（平均3.3分），停用MMF可显著减轻腹泻（6个月至15个月间TAC/MMF组平均评分变化-0.9，TAC单药治疗组为-1.8，p=0.03）。在有困扰症状的受者中，腹痛（从2.7降至1.8，p=0.003）、消化不良（从2.8降至2.3，p=0.012）和反流（从2.9降至1.7，p=0.007）随时间显著减轻，与是否使用MMF无关。
大多数接受TAC和MMF治疗的肾移植受者在移植后6个月出现困扰的胃肠道症状。虽然便秘仍然困扰，但到15个月时，消化不良、腹痛和反流随时间有所改善。腹泻仅在停用MMF后有所改善。
