C4d as a significant predictor for humoral rejection in renal allografts

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.