ABSTRACT
Introduction: Allograft failure due to immunological or non-immunological causes or a combination and patient death after transplantation are the 2 major causes of renal transplant loss. This paper reviews the various causes of allograft failure and explores strategies for its prevention. Results: Immune mechanisms of renal allograft failure are those mediated by acute and chronic rejection and are initiated by human leukocyte antigen (HLA) disparity between donor and recipient and increased recipient immune responsiveness that results in pre-sensitisation against HLA antigens. Better HLA matching between donor and recipient in both live-donor and cadaveric renal transplant recipients and the use of more potent immunosuppressants has reduced the incidence of acute rejection and resulted in improved overall graft survivals in recent years. However, as the use of more potent immunosuppression increases the risk of infections and malignancy, tailoring therapy by administering more potent immunosuppression to those at higher immunological risk may result in a better balance between the risks and benefits of immunosuppressive therapies. Ischaemia of the donor kidney, calcineurin inhibitor (CNI), mediated nephrotoxicity, reduced renal mass, hypertension, hyperlipidaemia and infections contribute to allograft failure through non-immunological mechanisms. Indeed, any cause of renal injury that results in nephron loss, either immunological or non-immunological, leads to reduced renal mass and initiates further renal damage due to hyperfiltration. Optimising these factors and minimising CNI nephrotoxicity are critical in reducing chronic allograft failure. Conclusions: Optimising each of these time-dependent and immunosuppressive drug-related factors would allow the maximisation of renal allograft function and survival.
Renal transplantation is the best form of renal replacement therapy for patients with end-stage renal failure (ESRF), in comparison to dialysis, as it is associated with higher patient survivals, lower hospitalisation rates and a superior quality of life. However, the ever-increasing numbers of new patients with ESRF and the limited but static supply of donor kidneys for transplant mandate that every renal transplant be optimised to achieve long-term patient and allograft survival. Patient death after transplantation and allograft failure are the 2 major causes of transplant loss. Although patient survival following a renal transplant is higher than that for ESRF patients on dialysis, renal transplant (RTx) recipients nevertheless remain at risk for death from cardiovascular disease due to their prior history of renal disease, hypertension, excess atherosclerotic vascular disease and other comorbidities such as diabetes, and at risk for death from infection because of the need for long-term immunosuppression. At the Singapore General Hospital, RTx recipients transplanted under cyclosporine (CsA)-based therapy between 1994 and 1999 had overall 1- and 5-year patient survivals of 99% and 97% for live-donor (LD) grafts and 96% and 92% for cadaveric (CAD) grafts and 1- and 5-year graft survivals of 98% and 92% for LD grafts and 87% and 79% for CAD grafts respectively.1 Among those who died or sustained graft loss after LD or CAD transplant, 6% of LD and 27% of CAD RTx, respectively, had died with a functioning allograft; the remainder lost their allografts to immunological and non-immunological causes. Thus, allograft failure over time after renal transplantation is a significant problem and poses challenges in the management of RTx.
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