In spite of the marked advances in surgical and immunosuppressive management protocols, the long-term survival of transplanted kidneys is still far from being satisfactory. Chronic antibody-mediated rejection has been known to be the most important cause of late-kidney allograft failure. Therefore, during the past few decades, transplant research has focused almost exclusively on identifying more powerful and minimally toxic immunosuppressive strategies to prevent acute rejection and alloimmune response toward the graft, whereas poor attention has been paid to non-immunological factors. However, the discrepancy between remarkable improvements in the prevention of acute rejection and failure to ameliorate long-term graft outcomes suggests that non-immunological injuries may have an important role in the progressive loss of graft function. Indeed, in addition to these complications, a number of other non-immunologic events may impair the function of transplanted kidneys and directly or indirectly lead to their failure. The most important nonimmune causes of late death-censored kidney graft failure include the quality of the donated kidney or mismatch between donor and recipients, adherence to prescriptions, drug toxicities, hypertension, metabolic complications such as dyslipidemia, new onset diabetes mellitus, hyperuricemia. As kidney graft resembles the remnant kidney, in which a low nephron mass initiates a self-perpetuating process of progressive renal function loss, the therapeutic tools able to retard progression of chronic renal disease are expected to be effective in kidney transplant patients as well. This presentation will show the etiopathlogy of non-immune mediated late graft failure and also the nephroprotective strategy to improve allograft outcomes.