Recurrent acute rejection remains a significant problem for recipients of renal allografts, with a large proportion of patients progressing to graft loss. The newly introduced Banff schema was used to determine whether the histologic pattern of acute rejection (severity and renal compartment scoring) could discriminate recurring from nonrecurring rejections and to examine whether objective rejection scoring had predictive value for rejection reversal and outcome. A total of 67 biopsies obtained from 50 patients with acute rejection were examined for the occurrence of recurrent allograft rejection. All patients were maintained on a cyclosporine-based triple immunosuppressive protocol and had biopsy-proven acute rejection without chronic changes. Rejection recurred in 13 patients (26%), of whom 4 further developed a third rejection. The majority of the patients developed this first rejection within 2 months posttransplantation. Demographics, prebiopsy renal function, immunosuppression, and peak serum creatinine level at the time of biopsy were similar in patients with multiple and single rejection. Peak levels of reactivity to panel of lymphocytes seemed higher in the group of patients with recurrent rejection, whereas HLA matching was similar for all patients. Banff scores for acute rejection did not discriminate patients at risk of rejection recurrence who had lower vascular (0.6 vs. 1.2), tubular (0.6 vs. 1.1), and lower cumulative SUM (3.0 vs. 4.5) scores on their first rejection when compared with patients with one rejection. Histological scoring was, however, significantly different when first and third episodes were compared in the same patient, indicating increased rejection severity with recurrence. Moreover, the rate of reversal of recurrent rejection by anti-lymphocyte therapy was significantly less than that of first rejection (P<0.05). In conclusion, these data demonstrate that Banff scoring correlated with rejection reversal and steroid responsiveness, yet rejection recurrence was independent of histological score of the first rejection. Furthermore, Banff schema provided an objective histological correlation to the poor clinical outcome seen with recurrent rejection. The data also suggest that patients with early mild rejection continue to be at risk for recurrence and graft loss.
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