As the percentage of older individuals with end stage kidney disease continue to grow, increased numbers of older patients are becoming kidney transplant candidates and recipients, however, these older patients have worse outcomes including increased likelihood of death and increased rates of infection and malignancy after transplantation as compared with younger patients. This vulnerability to outcomes related to immune senescence suggests that biologic aging in the immune system is the mechanism through which these adverse outcomes occur and that older transplant recipients are functionally over-immunosuppressed using current protocols of immunosuppression. We propose to utilize DNA methylation to accurately measure epigenetic age of peripheral blood mononuclear cells to determine whether this marker of biologic age, in combination with other clinical factors, can predict clinical outcomes after transplantation when evaluated before or after transplantation. In addition, we will determine whether transplantation and initiation of immunosuppression leads to acceleration of biologic aging. These findings can be applied to patient screening before and monitoring after transplantation and can allow for individualization of immune suppression medication regimens, allowing older patients with end stage kidney disease to benefit from transplantation with less risk of infectious complications.
Older solid organ transplant recipients are at increased risk for infectious complications and death compared with younger patients, however, the mechanism behind this increased vulnerability is unknown. This proposal will analyze changes in DNA methylation to calculate epigenetic age of peripheral blood mononuclear cells to determine whether increased biologic age correlates with adverse clinical outcomes after kidney transplantation, as well as whether transplantation leads to acceleration of aging. This study will lead to potential clinical applications in patient screening and customization of immunosuppression regimens, permitting avoidance of many potential infectious complications and improving clinical outcomes in older transplant recipients.
