Preventing renal transplant failure.
BACKGROUND
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 maximization of renal allograft function and survival.
Vathsala
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Department of Renal Medicine, Singapore General Hospital, Singapore.
D000818:Animals; D065095:Calcineurin Inhibitors; D006084:Graft Rejection / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D006973:Hypertension / Q000150:complications; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007511:Ischemia / Q000150:complications / Q000473:pathology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D016030:Kidney Transplantation; D013601:T-Lymphocytes / Q000276:immunology
D065095:Calcineurin Inhibitors; D006680:HLA Antigens; D007166:Immunosuppressive Agents