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表现急剧上升。肾移植最常见的适应症包括糖尿病(31%)、多囊肾病(12%)、高血压肾硬化(9%)和系统性红斑狼疮(3%)。尽管移植提高了存活率和生活质量，但它也伴随着风险的增加。 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，这种风险至少有一部分是由免疫抑制药物的暴露引起的，但其他假设已经援引了先前共同发病的重要性，甚至可能是先天免疫系统的激活。这些文献还强调了在几种自身免疫性风湿病中非常相似的癌症风险概况，包括系统性红斑狼疮(SLE)。这些患者的免疫系统过度活跃，会导致受影响组织的炎症和损伤。与器官移植患者一样，SLE患者也经常接受长期的免疫抑制治疗。除了药物可能增加患癌症的风险外，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，很难 区分这两个因素对系统性红斑狼疮等自身免疫性疾病癌症风险的独立影响。到目前为止，还没有人专门研究接受肾移植的SLE患者与非狼疮移植患者相比是否有更高的癌症风险。在目前的试点项目中，我们计划检查之前在美国肾脏数据系统(USRDS)中收集的数据，以研究肾移植患者的癌症风险，既有全面的，也有按适应症分层的(即，终末期肾病是否与系统性红斑狼疮或非狼疮相关)。我们的主要目标是研究肾移植受者的癌症风险，既包括总体风险，也包括按适应症分层的风险(即终末期肾病是否与系统性红斑狼疮和非狼疮相关)。在这个试点项目中要探索的主要假设是，与肾移植非狼疮适应症的患者相比，SLE患者肾移植后的癌症风险最高。我们还将在二次分析中比较其他重要癌症类型的癌症风险。USRDS中庞大的受试池为研究ESRD的癌症风险提供了一个独特的机会，这样我们就可以开始检查由于SLE等自身免疫性疾病而患有ESRD的患者在移植后患癌症的风险是否特别高。

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.