Late acute rejection in long-term renal allograft recipients. Diagnostic and predictive value of circulating activated T cells.

Episodes of acute rejection can occur in functional renal grafts even at a very late stage after transplantation. They are not necessarily due to patient noncompliance. The incidence of late acute rejection is commonly underestimated because the diagnosis generally requires histopathology in order to rule out other origins of declining graft function, even more so, as the typical signs of acute rejection as seen in the early posttransplantation period (sudden and rapid increase of creatinine serum level, inflammatory signs) are missing. Histology revealed acute rejection in 157 of 412 renal allograft recipients suffering from progressive graft deterioration between the 2nd and 18th year after Tx. Late acute rejection was clearly associated with elevated levels of activated HLA-DR+ T cells in the peripheral blood. These cells were characterized by flow cytometry to be postmitotic activated effector-T cells belonging to the CD4+ and CD8+ "memory" T cell pool. The high sensitivity (97%) and specificity (88%) of flow cytometric analysis allows for the discrimination between late acute rejection and other causes of deteriorating graft function (infection, toxicity, arteriopathy, chronic rejection). Additionally, this immune monitoring can predict the success of antirejection therapy as early as a few days after initiation of treatment while conventional parameters do not reflect the therapeutic result until 1-3 weeks later. In addition to this, peripheral T cell activation also seems to identify a subgroup of patients with chronic rejection who would respond, at least partially, to steroid bolus therapy. As a result, this parameter is very useful for the clinical management of patients suffering from late deterioration of renal graft function.