Mangino Margherita, Schena Francesco Paolo
Unita' di Nefrologia Dialisi e Trapianto, Dipartimento dell'Emergenza e dei Trapianti d'Organo (DETO), Universita' degli Studi, Bari, Italy.
G Ital Nefrol. 2010 Sep-Oct;27 Suppl 50:S75-80.
Kidney transplant is the best treatment option for renal failure. Over the years the 1-year patient survival has gradually increased, along with a reduction in acute rejection. The main causes of death in the late post-transplant period are cardiovascular disease, infections and malignancies. It is known that the incidence of cancer increases with the duration of post-transplant follow-up. Twenty years after transplantation, approximately 70% of patients on continuous immunosuppressive therapy present one or more tumor types. Some of the tumors that occur with a significantly higher frequency in transplant recipients compared with the general population are often associated with the reactivation of oncogenic viruses. Examples are herpes virus 8 (HHV8), implicated in Kaposi's sarcoma (KS), human papillomavirus (HPV), involved in squamous cell cancer of the skin, vulva, vagina and cervix, and Epstein-Barr virus (EBV), responsible for post-transplant lymphoproliferative disorder (PTLD). The type of drug used for the induction and maintenance of immunosuppression and the duration of treatment influence both the incidence and the type of cancer. For this reason, post-transplant malignancies often show a more aggressive behavior than tumors in the normal population. It is estimated that sarcomas occur 40 to 250 times more frequently in transplant recipients and are the leading cause of death from skin cancer after transplantation. The classic form of KS occurs in males and homosexuals. In the population of the Mediterranean area, KS is often associated with HHV8 infection that is reactivated by immunosuppression. The reduction or suspension of immunosuppressive therapy is the first step in the treatment of post-transplant KS. The second approach is chemotherapy. Since m-TOR, the target of sirolimus, is altered in many tumors, sirolimus may be an effective tool. Sirolimus inhibits not only cell proliferation but also tumor neovascularization by reducing VEGF production and inhibiting VEGF receptor signaling in endothelial cells. In conclusion, new strategies must be developed to reduce cancer mortality in transplant recipients while ensuring adequate immunosuppression to preserve the transplanted organ. One such strategy is the adoption of immunosuppressive regimens tailored to individual patients' medical history.
肾移植是肾衰竭的最佳治疗选择。多年来,患者1年生存率逐渐提高,急性排斥反应也有所减少。移植后期的主要死亡原因是心血管疾病、感染和恶性肿瘤。众所周知,癌症发病率会随着移植后随访时间的延长而增加。移植20年后,约70%接受持续免疫抑制治疗的患者会出现一种或多种肿瘤类型。与普通人群相比,移植受者中某些肿瘤的发生频率显著更高,这些肿瘤通常与致癌病毒的重新激活有关。例如,与卡波西肉瘤(KS)相关的疱疹病毒8型(HHV8)、与皮肤、外阴、阴道和宫颈癌的鳞状细胞癌有关的人乳头瘤病毒(HPV),以及导致移植后淋巴细胞增生性疾病(PTLD)的爱泼斯坦-巴尔病毒(EBV)。用于诱导和维持免疫抑制的药物类型以及治疗持续时间会影响癌症的发病率和类型。因此,移植后恶性肿瘤通常比普通人群中的肿瘤表现出更具侵袭性的行为。据估计,移植受者中肉瘤的发生频率比常人高40至250倍,是移植后皮肤癌死亡的主要原因。KS的经典形式发生在男性和同性恋者中。在地中海地区人群中,KS常与因免疫抑制而重新激活的HHV8感染有关。减少或停用免疫抑制治疗是移植后KS治疗的第一步。第二种方法是化疗。由于西罗莫司的靶点m-TOR在许多肿瘤中发生改变,西罗莫司可能是一种有效的工具。西罗莫司不仅抑制细胞增殖,还通过减少VEGF生成和抑制内皮细胞中的VEGF受体信号传导来抑制肿瘤新生血管形成。总之,必须制定新策略以降低移植受者的癌症死亡率,同时确保足够的免疫抑制以保护移植器官。一种这样的策略是采用根据个体患者病史量身定制的免疫抑制方案。