Research Awards Recipients

Lay Abstract

Background and Purpose Kidney transplantation is a gold standard treatment for the end-stage of kidney diseases. Despite improvements in short-term outcomes, long-term patient and transplant kidney survival remain suboptimal due to the toxic side effects associated with the long-term use of immune suppression drugs. Some transplantation patients require second-time kidney transplantation. The ultimate goal of transplantation research is to induce kidney graft-specific immune tolerance in transplant recipients, which allows long-term implanted kidney survival while avoiding the need for immunosuppression and its associated adverse effects. The objective of the study is to discover a new treatment for patients who have kidney transplantation to improve patient health and life quality while reducing the financial burden. Recently we found that a new type of non-coding ribonucleic acid (RNA) called circular RNA might be a master regulator in controlling immune rejection. circular RNA is back-spliced from a gene and has a closed-loop structure. Our preliminary study shows that this circular RNA is over-expressed in immune reactive cells which play a vital role in determining immune rejection and immune acceptance of a transplanted kidney. Inhibition of this RNA can change immune cells from an immune reactive state into an immune-suppressive state, implying that this RNA could be a novel target for the development of a new therapy for treating transplant patients. This study aims to investigate whether this circular RNA is a new therapeutic target for preventing immune rejection in kidney transplantation and to develop a novel treatment to protect transplant patients from immune rejection. Method and Outcome We will investigate the effect of this circular RNA in preventing immune rejection in kidney transplantation using a mouse transplantation model. Recipient mice will be treated with inhibitors of this circular RNA to inhibit this circular RNA expression. Kidney function, overall survival, the immune response of transplant mice, and histopathological changes of transplanted kidneys will be determined to assess the impact of the treatment on protecting transplanted kidneys from immune rejection. We expect that this new treatment will significantly prolong transplant recipient survival and free patients from lifetime immunosuppressive drug use. Conclusion and Relevance to Patients The success of the study will provide a framework for the development of new treatments for preventing immune rejection in kidney transplantation. This will, in turn, lead to improvements in the development of new and powerful therapies to greatly improve the survival and quality of life of kidney transplant recipients. New therapy will reduce the risk for second-time kidney transplantation, which allows more patients with end-stage kidney failure will have the opportunity for kidney transplantation.