Abstract

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.

中文翻译：

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实体器官移植的代谢后果

摘要

代谢并发症影响超过 50% 的实体器官移植受者。这些包括移植后糖尿病、非酒精性脂肪肝、血脂异常和肥胖。免疫抑制和移植后体重增加会进一步加剧先前存在的代谢疾病。由于体重增加、久坐不动的生活方式和免疫抑制情况下的次优饮食习惯，患者在移植后从由终末器官疾病引起的恶病质状态转变为促合成代谢状态。特定的免疫抑制剂具有不同的代谢作用，尽管所有基础/维持免疫抑制剂（钙调磷酸酶抑制剂、mTOR 抑制剂）都会增加代谢疾病的风险。在这篇综合综述中，我们总结了这些不同代谢并发症的分子发病机制的新兴知识，以及对这些条件的潜在遗传贡献（接受者 +/- 捐赠者）。这些代谢并发症影响移植物和患者的生存，特别是增加心血管和癌症相关死亡的风险。提供了移植后代谢状况的预防和治疗管理的当前证据，同时强调了转化研究未来途径的差距。