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Published on: April 28, 2013
C4d deposits in acute "cell-mediated" rejection: a marker for renal prognosis?
M Neves1, P Cotovio, S Machado
1Department of Nephrology, Hospitais da Universidade de Coimbra, Coimbra, Portugal. martaraq_neves@hotmail.com
Insights
C4d deposits in acute cell-mediated kidney transplant rejection do not worsen graft survival or function. This study found no significant difference in graft outcomes for C4d-positive versus C4d-negative biopsies in either type I or type II acute rejection.
Area of Science:
- Nephrology
- Transplant Immunology
- Pathology
Background:
- C4d deposition in renal allografts typically indicates antibody-mediated rejection.
- The prognostic significance of C4d in cell-mediated rejection is not well-established.
- This study investigates the impact of C4d on graft survival and function in acute cell-mediated rejection.
Purpose of the Study:
- To determine if C4d deposition in acute cell-mediated rejection affects renal allograft outcomes.
- To compare graft survival and function between C4d-positive and C4d-negative biopsies in different types of acute rejection.
Main Methods:
- Retrospective analysis of 79 renal transplant recipients with acute rejection (AR) between 2005-2010.
- Patients were classified by Banff 2003 criteria into type I (69.6%) and type II (30.4%) AR.
- Biopsies were analyzed for C4d staining, comparing C4d-negative and C4d-positive groups within each AR type.
Main Results:
- In type I AR (n=55), graft survival and eGFR were similar between C4d-negative and C4d-positive groups at 1 and 2 years.
- In type II AR (n=24), graft survival and eGFR also showed no significant differences between C4d-negative and C4d-positive subgroups.
- Graft loss rates were not significantly different between C4d-positive and C4d-negative patients in either AR type.
Conclusions:
- C4d staining in acute cell-mediated rejection does not appear to negatively impact renal allograft prognosis.
- The presence of C4d in cell-mediated rejection does not predict worse graft function or survival.
- These findings suggest C4d status alone may not be sufficient to stratify risk in cell-mediated rejection.
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.
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