C4d Deposits in Acute “Cell-Mediated” Rejection: A Marker for Renal Prognosis?

Abstract Background Accumulation of C4d along peritubular capillaries (PTC) of renal allografts is normally attributed to antibody-mediated rejection. The prognostic implication of these deposits associated with “cell-mediated” rejection on graft survival remains uncertain. Our study aims to evaluate the impact of C4d deposits along PTC of patients with acute cell- mediated rejection on graft function and survival. Methods We retrospectively analyzed patients transplanted between 2005 and 2010 with histopathologic diagnosis of acute rejection (AR). Eleven patients with “pure” antibody-mediated rejection were excluded. The remaining 79 patients were divided into two groups according to type of AR by Banff 2003 criteria: type I (69.6%) versus type II (30.4%). In each group, comparisons were made between C4d-negative (−) and C4d-positive (+) biopsies. Results Fifty-five patients presented with type I AR: 35 (63.6%) C4d− and 20 (36.4%) C4d+. Twenty-four patients presented with type II AR: 13 (54.2%) C4d− and 11 (45.8%) C4d+. In the type I AR group, graft survival at the first and second years was similar in C4d− and C4d+ patients (94% and 91% versus 75% and 75%, respectively, log-rank P = .26). No differences were encountered in estimated glomerular filtration rate (eGFR) between subgroups at the first, second, and final years of follow-up. Graft loss occurred in 14.7% of C4d− patients versus 25% in C4d+ patients ( P = NS). In the type II AR group, graft survival at the first and second years was similar in C4d− and C4d+ patients (85% and 85% versus 72% and 61%, respectively, log–rank P = .50). No differences were encountered in eGFR between subgroups at the first, second, and final years of follow-up. Graft loss occurred in 30.8% of C4d− patients versus 45.5% in C4d+ patients ( P = NS). Conclusion Our results suggest that detection of C4d staining in acute “cell-mediated” rejection does not imply a worse renal prognosis.