Immunologic risk factors for chronic renal allograft dysfunction.
Tissue injury is probably the central feature leading to CRAD, whether that injury is produced by immunological or nonimmunological factors. Tissue injury may expose cryptic antigens that, in an allogeneic situation, stimulate immune responses that further increase tissue damage. With acute rejection the immunological factor most strongly predictive of CRAD, HLA mismatches may facilitate rejection or otherwise lead to CRAD. However, clinical studies have not always demonstrated an increasing risk of CRAD with increased numbers of HLA mismatches. Antibodies produced against HLA or other donor-specific antigens may play a role in initiating the CRAD process or may occur secondary to tissue damage. Several human transplant studies have demonstrated an association between anti-HLA or anti-B cell antibodies and CRAD. In animal models of CRAD, antibodies are produced against antigens associated with glomerular and tubular basement membranes and mesangial cells, as well as antigens associated with vascular endothelial cells. The pathogenetic significance of these antibody responses is unclear at this time, but these responses may interfere with repair processes that follow tissue injury or otherwise facilitate mechanisms leading to CRAD. Whether similar antibody responses against components of basement membrane and mesangial cells occur in human renal transplant patients with CRAD is not yet known. The most effective way to prevent CRAD is to prevent tissue damage, especially immunity-related injury that involves maintaining appropriate immunosuppression. When using calcineurin inhibitors for immunosuppression, there is a risk of chronic calcineurin inhibitor-associated nephrotoxicity. Nonnephrotoxic immunosuppressive agents, such as sirolimus and mycophenolate mofetil, may be considered in therapeutic strategies designed to prevent acute rejection and to minimize renal tissue damage due to nephrotoxic drugs.
Paul
L C
LC
Leiden University Medical School, The Netherlands.
D000818:Animals; D000906:Antibodies / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology; D023421:Models, Animal; D012307:Risk Factors
D000906:Antibodies; D006680:HLA Antigens