Mechanism, pathophysiology, diagnosis, and management of renal transplant rejection

Abstract

In recent years, there has been a steady progress in basic research (immunogenetics and cellular immunology) that helped us in understanding the mechanisms underlying allograft rejection. Several laboratory tests were developed, and the results were shown to correlate with clinical rejection. However, most of these studies have not found a place in clinical practice because of their nonspecificity, lack of sensitivity, time lag, added expense, and inconvenience. The commonly employed diagnostic tests (i.e., renal transplant ultrasound and 131I hippuran scintigram) are helpful in differentiating rejection from other causes of graft malfunction. The specific renal parenchymal disease, such as acute or chronic rejection or de novo or recurrent glomerular disease, contributing to graft malfunction can only be diagnosed by renal histopathologic study. Because hyperacute and accelerated acute rejections are irreversible and necessitate graft nephrectomy, measures should be taken to prevent this problem. High-dose corticosteroids still remain the mainstay of therapy for acute cellular rejection. In the case of steroid-resistant rejections, treatment with ALG or OKT3 appears promising. As there is no effective therapy for chronic allograft rejection, usual measures of delaying the progression of chronic renal failure should be employed, and patients should be advised to return to maintenance dialysis before they develop uremic symptoms. If current experiments demonstrating selective immunosuppression with monoclonal antibodies are found successful in human trials, one can expect further improvement in the outcome of renal transplantation.