Cancer risk after renal transplant in autoimmune disease

描述（由申请人提供）：在过去的三十年中，终末期肾病（ESRD）的患病率和肾移植的性能急剧上升。肾移植最常见的适应症包括糖尿病（31%）、多囊肾病（12%）、高血压性肾硬化症（9%）和系统性狼疮（3%）。虽然移植可以提高生存率和生活质量，但它与增加的风险有关。 用于某些癌症，包括淋巴增生性癌症（特别是非霍奇金淋巴瘤，NL）、肺癌、皮肤癌、肝癌和外阴阴道癌。目前认为，这种风险中至少有一部分是由免疫抑制药物暴露引起的，但其他假设已经引起了先前合并症的重要性，甚至可能是先天免疫系统激活。 文献还强调了几种自身免疫性风湿性疾病（包括系统性红斑狼疮（SLE））中非常相似的癌症风险特征。这些患者的免疫系统过度活跃，导致受影响组织的炎症和损伤。与器官移植患者一样，SLE患者也经常接受免疫抑制治疗的长期治疗。除了药物可能增加癌症风险外，有证据表明SLE疾病活动本身与某些恶性肿瘤的风险增加有关。由于药物和疾病活动之间的相关性， 区分这两个因素对自身免疫性疾病（如SLE）癌症风险的独立影响。 到目前为止，还没有人专门研究过接受肾移植的SLE患者与非狼疮移植患者相比是否有更高的癌症风险。在当前的试点项目中，我们计划检查美国肾脏数据系统（USRDS）中先前收集的数据，以研究肾移植患者的癌症风险，包括总体风险和按适应症分层的风险（即ESRD是否与SLE或非狼疮原因相关）。我们的主要目的是研究肾移植受者的癌症风险，包括总体风险和按适应症分层的风险（即ESRD是否与SLE相关，而不是与非狼疮原因相关）。在这个试验项目中要探索的主要假设是，与非狼疮肾移植指征的患者相比，SLE患者雷纳移植后的癌症风险最高。我们还将在次要分析中比较其他重要癌症类型的癌症风险。USRDS中庞大的受试者库提供了一个独特的机会来研究按ESRD原因分层的癌症风险，因此我们可以开始检查由于自身免疫性疾病（如SLE）导致的ESRD患者在移植后是否具有特别高的癌症风险。 公共卫生相关性：终末期肾病（ESRD）的肾移植在过去三十年中有所增加。注意到移植后某些癌症的风险增加，包括非霍奇金淋巴瘤和肺、皮肤、肝脏和外阴阴道区域的肿瘤。与此同时，患有慢性自身免疫性疾病系统性红斑狼疮（SLE）的患者也有患类似癌症的风险，SLE患者的肾脏有炎症和损伤的风险，这些疾病可能进展为ESRD。目前认为，一些增加的癌症风险是由用于治疗SLE和预防移植后排斥反应的免疫抑制药物引起的。然而，还有其他可能导致癌症风险增加的原因，包括免疫系统异常。这项初步研究将检查SLE患者在接受终末期肾病移植后患癌症的风险是否高于未患SLE但也接受肾移植的患者。这项研究将回答这样一个问题，即患有自身免疫性疾病（如SLE）的患者在移植后是否有异常高的患癌风险。

DESCRIPTION (provided by applicant): The prevalence of end-stage renal disease (ESRD) and the performance of renal transplantation have risen dramatically in the past three decades. The most common indications for renal transplantation include diabetes (31%), polycystic kidney disease (12%), hypertensive nephrosclerosis (9%) and systemic lupus (3%). Although transplantation improves both survival and quality of life, it is associated with an increased risk for certain cancers including lymphoproliferative cancers (especially non-Hodgkin lymphoma, NL), lung cancer, skin cancer, liver cancer, and vulvovaginal cancers. It is currently believed that at least some of this risk is conferred by immunosuppressive drug exposures, but other hypotheses have invoked the importance of prior co-morbidity, and perhaps even innate immune system activation. The literature also highlights a very similar cancer risk profile in several autoimmune rheumatic diseases, including systemic lupus erythematosus (SLE). These patients have an overactive immune system that causes inflammation and damage in affected tissue. Like organ transplant patients, SLE patients often also undergo long-term treatment with immunosuppressive therapy. In addition to possible increased risk for cancer conferred by medications, there is evidence that SLE disease activity itself is associated with increased risk of certain malignancies. Due to correlations between drugs and disease activity, it is difficult to differentiate the independent effects of these two factors, on cancer risk in autoimmune diseases like SLE. To date, no one has specifically examined whether those patients with SLE who undergo renal transplantation have an increased risk of cancer compared to non-lupus transplant patients. In the current pilot project, we plan to examine previously collected data in the United States Renal Data System (USRDS) to study cancer risk in renal transplant patients, both over-all, and stratified by indication (that is, whether ESRD is related to SLE versus non-lupus causes). Our primary aims are to study cancer risk in renal transplant recipients, both over-all, and stratified by indication (i.e. whether ESRD is related to SLE versus non-lupus causes). The primary hypothesis to be explored in this pilot project is that cancer risk after rena transplantation is highest in SLE patients, compared to patients with non-lupus indications for renal transplantation. We will additionally compare cancer risk for other important cancer types, in secondary analyses. The enormous pool of subjects in the USRDS affords a unique opportunity to study cancer risk stratified by reason for ESRD, so that we can begin to examine the question of whether patients with ESRD due to autoimmune diseases like SLE have a particularly high risk of cancer, post-transplantation. PUBLIC HEALTH RELEVANCE: Renal transplantation for end stage renal disease (ESRD) has increased during the last thirty years. An increased risk of certain cancers including non-Hodgkin's Lymphoma and tumors of the lung, skin, liver, and vulvovaginal areas following transplantation has noted. At the same time, patients with a chronic autoimmune disorder, systemic lupus erythematosus (SLE), who are at risk for inflammation and damage to their kidneys which can progress to ESRD, are also at risk for developing similar cancers. It is currently believed that some of the increased risk of cancer is conferred by immunosuppressive drugs used to treat SLE and prevent rejection following transplantation. However, there are other possible causes of the increased risk of cancer including abnormalities of the immune system. This pilot study will examine whether patients with SLE following transplantation for ESRD are at increased risk of cancer compared to patient without SLE who also had a renal transplant. This study will answer the question as to whether patients with an autoimmune disorder such as SLE have an unusually high risk of developing cancer post-transplantation.