Capillary Deposition of Complement C4d and C3d in Pediatric Renal Allograft Biopsies


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Abstract

Background.Peritubular capillary deposition of C4d (C4dPTC) is a marker of antibody-mediated alloresponse and is associated with poor graft survival in adults. C3dPTC has received less attention; its significance is unclear. To date no information has been gained in children.Methods.The prevalence of C4dPTC and C3dPTC in pediatric renal allograft biopsies (n=77, 31 cadaveric kidneys) was analyzed retrospectively. Associations with histology, donor-specific antibodies (DSAs), and outcome were investigated.Results.The overall prevalence of C4dPTC and C3dPTC was 52% and 48%, respectively. C3dPTC was associated with C4dPTC (P<0.0001). Thirty-six percent of acute rejections were cellular, 28% were humoral, and 36% were combined cellular and humoral. C3dPTC was found in 57% of acute rejection biopsies. C4dPTC, but not C3dPTC, was associated with accumulation of polymorphonuclear cells in peritubular capillaries (P=0.02). Fifty-one percent of late biopsies (>6 months posttransplantation) had features of chronic allograft nephropathy: 50% were C4dPTC positive, and 50% were C3dPTC positive. C4dPTC positive chronic allograft nephropathy biopsies had more transplant glomerulopathy (P=0.020) and mesangial matrix increase (P=0.026). C3dPTC tended to be associated with transplant glomerulopathy (P=0.06), but not with mesangial matrix increase. C4dPTC was correlated with DSA (P=0.011). Excluding early nonrejection graft losses, more grafts were lost in the C4dPTC positive group (P=0.019). C3dPTC was not associated with DSA or graft outcome.Conclusions.Our results support C4dPTC being a hallmark of humoral rejection in pediatric renal transplantation; its presence was associated with DSA and poorer immunologic graft outcome. In contrast, C3dPTC, although highly associated with C4dPTC, did not correlate with DSA or outcome.

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