Bhat Mamatha, Usmani Shirine E, Azhie Amirhossein, Woo Minna
Multi Organ Transplant program and Division of Gastroenterology & Hepatology, University Health Network, Ontario M5G 2N2, Department of Medicine, University of Toronto, Ontario, Canada.
Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
Endocr Rev. 2021 Mar 15;42(2):171-197. doi: 10.1210/endrev/bnaa030.
Metabolic complications affect over 50% of solid organ transplant recipients. These include posttransplant diabetes, nonalcoholic fatty liver disease, dyslipidemia, and obesity. Preexisting metabolic disease is further exacerbated with immunosuppression and posttransplant weight gain. Patients transition from a state of cachexia induced by end-organ disease to a pro-anabolic state after transplant due to weight gain, sedentary lifestyle, and suboptimal dietary habits in the setting of immunosuppression. Specific immunosuppressants have different metabolic effects, although all the foundation/maintenance immunosuppressants (calcineurin inhibitors, mTOR inhibitors) increase the risk of metabolic disease. In this comprehensive review, we summarize the emerging knowledge of the molecular pathogenesis of these different metabolic complications, and the potential genetic contribution (recipient +/- donor) to these conditions. These metabolic complications impact both graft and patient survival, particularly increasing the risk of cardiovascular and cancer-associated mortality. The current evidence for prevention and therapeutic management of posttransplant metabolic conditions is provided while highlighting gaps for future avenues in translational research.
代谢并发症影响超过50%的实体器官移植受者。这些并发症包括移植后糖尿病、非酒精性脂肪性肝病、血脂异常和肥胖。免疫抑制和移植后体重增加会使先前存在的代谢疾病进一步恶化。由于体重增加、久坐不动的生活方式以及免疫抑制情况下不理想的饮食习惯,患者从终末期器官疾病导致的恶病质状态转变为移植后的合成代谢状态。尽管所有基础/维持免疫抑制剂(钙调神经磷酸酶抑制剂、mTOR抑制剂)都会增加代谢疾病的风险,但特定的免疫抑制剂具有不同的代谢作用。在这篇综述中,我们总结了这些不同代谢并发症分子发病机制的最新知识,以及这些情况潜在的遗传贡献(受者+/-供者)。这些代谢并发症影响移植物和患者的生存,尤其增加了心血管疾病和癌症相关死亡率的风险。本文提供了移植后代谢状况预防和治疗管理的现有证据,同时强调了转化研究未来方向的差距。