C4d in pediatric renal allograft biopsies: a marker for negative outcome in steroid-resistant rejection.
Recently, deposition of C4d, reflecting complement activation via the classical pathway, has been established as marker of antibody-mediated rejection. As C4d can be detected in paraffin sections, it allows for retrospective analysis in populations with low case loads, such as in pediatric transplantation. In this study we re-evaluated consecutive renal transplant biopsies obtained since 1990 in 36 children (18 boys, 18 girls) who had received their allograft (nine living, 27 cadaveric) at an age of 10.12+/-4.4 yr. Clinical indications for biopsy were 16 acute steroid resistant rejections (ASRs), 11 chronic rejections and nine other diagnoses. Overall, C4d deposition was found in nine cases (25%), eight of them with diagnosed ASR. Six out of these eight allografts were lost during 36 months of clinical follow-up, a significantly higher rate than in C4d-negative biopsies (p<0.05). C4d status therefore turned out to be an excellent predictor for inferior graft survival following ASR. None of the other histopathologic markers were sensitive for humoral rejections. In conclusion, the high prevalence of C4d-positive staining in ASR demonstrates the importance of the humoral part of the immune system in pediatric transplantation. The worse outcome of C4d-positive rejections despite massive immunosuppressive therapy clearly indicates the need for innovative therapies in this high-risk population.
Vargha
Regina
R
Department of Paediatrics, AKH, Medical University of Vienna, Vienna, Austria.
Mueller
Thomas
T
Arbeiter
Klaus
K
Regele
Heinz
H
Exner
Markus
M
Csaicsich
Dagmar
D
Aufricht
Christoph
C
D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001706:Biopsy; D002102:Cadaver; D016009:Chi-Square Distribution; D002648:Child; D003181:Complement C4 / Q000378:metabolism*; D003404:Creatinine / Q000493:pharmacokinetics; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology; D019520:Living Donors / Q000706:statistics & numerical data; D008297:Male; D009392:Nephrectomy; D011237:Predictive Value of Tests; D015995:Prevalence; D012044:Regression Analysis; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013256:Steroids / Q000276:immunology / Q000627:therapeutic use*; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D015415:Biomarkers; D003181:Complement C4; D013256:Steroids; D003404:Creatinine