Grant Number:	1R03CA165139-01A1 Interpret this number
Primary Investigator:	Ramsey-Goldman, Rosalind
Organization:	Northwestern University At Chicago
Project Title:	Cancer Risk After Renal Transplant in Autoimmune Disease
Fiscal Year:	2012

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.





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