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 d ue to patient noncompliance. The incidence of late acute rejection is commonly underestimated because the diagnosis generally requires histo pathology in order to rule out other origins of declining graft functi on, even more so, as the typical signs of acute rejection as seen in t he early posttransplantation period (sudden and rapid increase of crea tinine serum level, inflammatory signs) are missing. Histology reveale d acute rejection in 157 of 412 renal allograft recipients suffering f rom progressive graft deterioration between the 2nd and 18th year afte r Tx. Late acute rejection was clearly associated with elevated levels of activated HLA-DR(+) T cells in the peripheral blood. These cells w ere characterized by flow cytometry to be postmitotic activated effect or-T cells belonging to the CD4(+) and CD8(+) ''memory'' T cell pool. The high sensitivity (97%) and specificity (88%) of flow cytometric an alysis allows for the discrimination between late acute rejection and other causes of deteriorating graft function (infection, toxicity, art eriopathy, chronic rejection). Additionally, this immune monitoring ca n predict the success of antirejection therapy as early as a few days after initiation of treatment while conventional parameters do not ref lect the therapeutic result until 1-3 weeks later. In addition to this , peripheral T cell activation also seems to identify a subgroup of pa tients with chronic rejection who would respond, at least partially, t o steroid bolus therapy. As a result, this parameter is very useful fo r the clinical management of patients suffering from late deterioratio n of renal graft function.