Kidney transplantation is a life-saving procedure for patients with end-stage kidney disease. Although the short-term organ survival post-transplantation has improved dramatically over the past decades, the long-term outcomes remain unsatisfied with the survival half-lives for transplanted renal grafts still about 10 years. In addition, organ shortage is a global crisis which has stimulated new approaches on expansion of the donor pool by using marginal organs. However, the employment of marginal organs has a significantly higher incidence of delayed graft function and lower graft survival rate compared with standard criteria donors. Therefore, there is an urgent need for new strategies to improve the long-term graft outcomes. In this proposal, a novel hypothesis that rescue macula densa NOS1 expression by renal alkalization with bicarbonate improves transplanted graft outcomes will be tested. The findings of the present proposal will provide a novel strategy with potential translational significance that could be applied to either donors or recipients during kidney transplantation. Additionally, the underlying mechanisms and potential targets will be examined. Renal alkalization to enhance the expression of macula densa NOS1 expression in donors or recipients is anticipated to be a simple and effective method that is used in the expansion of the donor pool and improvement of long-term graft survival.