Histological Markers of Humoral Rejection in Renal Transplant Patients

Abstract

Diagnosis of “suspicious humoral rejection” can be formulated in the presence of peritubular capillary (PTC) C4d deposition and one of the following tissue changes: (1) acute tubular necrosis, (2) glomerulitis or presence of polymophonuclear leukocytes or monocytes in PTC, or (3) arteritis. From January 2004 to October 2006, we performed immunohistochemical staining with anti-C4d antibody on 54 renal biopsies from 39 renal transplant patients. In 25 biopsies we observed diffuse ( n = 13) or focal ( n = 12) C4d deposition. Based on C4d-positivity, patients were divided into three groups: group 1 included 19 C4d-negative patients; group 2, 10 patients with diffuse C4d-positivity; and group 3, 10 patients with focal C4d-positivity. Panel-reaction antibody–positive tests were associated with diffuse C4d-positivity: 50% of group 2 patients showed a positive test, while no group 1 or 3 patients had a positive test ( P < .001). Glomerulitis was observed in six biopsies and associated with diffuse C4d staining. Graft loss occurred in 3/10 group 2 patients (30%); 2/19 group 1 patients (10.5%), and 1/10 group 3 patients (10%). Viral infections were experienced in the year of the biopsy by 50% of group 1 patients 80% of group 2 patients, and 100% of group 3 patients ( P < .025), indicating a significantly greater number of infections among patients with C4d-positive biopsies. In eight cases, anti-thymocyte globulin was administered less than 21 days before the biopsy: four had diffuse and four had focal C4d positivity.