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C4d as a significant predictor for humoral rejection in renal allografts
Chen Jianghua1, Xie Wenqing, Wang Huiping
1Kidney Disease Center of the First Affiliated Hospital, Medical School of Zhejiang University, Hangzhou, China. zykidney@mail.hz.zj.cn
Insights
C4d deposition in renal allografts is a valuable diagnostic marker for acute rejection, particularly humoral rejection. Positive C4d staining predicts poorer graft survival and resistance to treatment, aiding clinical management.
Area of Science:
- Nephrology
- Immunology
- Transplantation Medicine
Background:
- Acute rejection remains a significant challenge in renal transplantation.
- Identifying reliable biomarkers for acute rejection is crucial for optimizing patient outcomes.
Purpose of the Study:
- To evaluate the diagnostic and clinical significance of C4d deposition in renal allografts experiencing acute rejection.
- To assess the correlation between C4d positivity and graft survival, treatment response, and rejection severity.
Main Methods:
- Analysis of 158 renal graft biopsies classified using Banff-97 criteria.
- Immunohistochemical detection of C4d deposition.
- Correlation of C4d status with clinical parameters including serum creatinine levels and treatment outcomes.
Main Results:
- C4d positivity was observed in 100% of hyperacute rejection (HAR), 77.8% of acute vascular rejection (AVR), and 37.5% of acute cellular rejection (ACR) cases.
- C4d-positive patients exhibited significantly higher peak and trough serum creatinine levels post-rejection compared to C4d-negative patients.
- C4d positivity was associated with increased resistance to steroid therapy and a higher rate of graft loss.
Conclusions:
- C4d deposition is a valuable diagnostic marker for acute rejection, especially humoral rejection.
- C4d positivity serves as a significant predictor of renal allograft survival.
- C4d assessment aids in guiding treatment strategies for acute rejection.
Objective:
To determine the diagnostic and clinical significance of C4d accumulation in renal allografts followed by acute rejection.
Methods:
A total of 158 graft biopsies performed from December 1997 to December 2002 were classified, according to the Banff-97 criteria, into hyperacute rejection (HAR, three cases), acute vascular rejection (AVR, 27), acute cellular rejection (ACR, 24), borderline rejection (BR, 38), acute tubular necrosis (ATN, five), stable graft function (SGF, 30) and baseline kidney (31). Immunohistochemical technique was used to determine the C4d deposition level.
Results:
The percentages of C4d positive in HAR, AVR, ACR, BR, ATN, SGF and baseline kidney groups were 100% (3/3), 77.8% (21/27), 37.5% (9/24), 23.7% (9/38), 0% (0/5), 3.3% (1/30), 0% (0/31), respectively. In acute rejection patients, the peak serum creatinine (sCr) level in C4d(ptc)-positive group (41 cases) was 334.82 +/- 238.37 micromol/L, with that of C4d(ptc)-negative group (47 cases) being 220.20 +/- 176.94 micromol/L (p < 0.01). After treatment, the trough sCr level in C4d(ptc)-positive group and C4d(ptc)-negative group were 176.87 +/- 111.80 and 121.75 +/- 34.59 micromol/L (p < 0.01), respectively. In each AVR, ACR and BR subgroups, the peak sCr level, the trough sCr level, after 3 or 6 months of AR, the sCr level in C4d(ptc)-positive subgroup was higher than that of C4d(ptc)-negative subgroup. There were more resistance against steroid therapy [65.9% (27/41) vs. 36.2% (17/47), p = 0.005] and a higher rate of graft loss [29.3% (12/41) vs. 6.4% (3/47), p = 0.001] in C4d(ptc)-positive group than those of C4d(ptc)-negative group. In each C4d(ptc)-positive subgroup of AVR, ACR and BR the complete reversion was 57.1, 56 and 66.7%, respectively, it is almost same.
Conclusion:
The C4d deposition level is of great value in diagnosis of acute rejection caused by humoral immune components. It is a significant predictor of graft survival and will be of great help when treating acute rejection.
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