C4d-Positive Renal Allograft Rejection Biopsies in Cyclosporine-Treated Patients: Single-Center Incidence and Outcome

• Published in: Transplantation proceedings 2010-07, Vol.42 (6), p.2214-2217
• Main Authors: Valente, M, Furian, L, Marchini, F, Marino, S, Cardillo, M, Rigotti, P, Aiello, F.B
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Biopsy; Complement C4b - analysis; Creatinine - blood; Epidemiology; Female; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Fundamental immunology; General aspects; Graft Rejection - epidemiology; Graft Rejection - immunology; Graft Rejection - pathology; Histocompatibility Testing - methods; Humans; Incidence; Kidney Transplantation - immunology; Kidney Transplantation - mortality; Kidney Transplantation - pathology; Kidney Transplantation - physiology; Male; Medical sciences; Middle Aged; Peptide Fragments - analysis; Public health. Hygiene; Public health. Hygiene-occupational medicine; Retrospective Studies; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Survival Rate; T-Lymphocytes - immunology; Tissue, organ and graft immunology; Treatment Outcome
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2010.05.037

Abstract T cell–mediated acute rejection (ATCMR) in renal transplant patients can have an antibody-mediated component. The aim of this study was to evaluate the incidence of renal biopsies showing ATCMR with C4d immunoreactivity and the correlation between C4d-positive ATCMRs and graft outcomes. We studied 216 renal transplant patients receiving cyclosporine-based immunosuppression (mean follow-up = 203.5 ± 42.5 months). Of these, 79 experienced biopsy-proven ATCMR (group 1), whereas 137 did not show clinical or laboratory evidence of ATCMR (group 2). Mean serum creatinine levels were evaluated at 6 months, as well as 2 and 5 years after transplantation. The number of graft losses due to interstitial fibrosis and tubular atrophy (IF/TA) was greater in group 1 than in group 2 ( P < .001 and P < .02, respectively), while graft survival was lower ( P < .03). Staining with anti-C4d antibody was performed in 61/77 type I ATCMR biopsies: seven cases showed diffuse C4d positivity with CD68+ monocytes in peritubular capillaries observed in all cases. Three cases showed focal C4d positivity. Two ATCMRs were steroid, resistant. Graft loss due to IF/TA occurred in 4/7 patients (57.1%) who had previously experienced ATCMRs with diffuse C4d positivity; whereas it occurred in 5/51 patients (9.8%) with previous C4d negative ATCMRs ( P < .001). Patients with focal C4d positivity did not undergo graft loss due to IF/TA. In conclusion, at our center the diffuse C4d positivity that occurred in 11.4% of type I ATCMRs was associated with a poor prognosis.