Glomerular C3c deposition and intravascular macrophage accumulation in early humoral renal allograft rejection signifies a poor short‐term outcome

Abstract

C4d deposition in the walls of peritubular capillaries is considered the key phenomenon in the histopathological diagnosis of humoral, i.e. antibody‐mediated, allograft rejection. We have earlier proposed that deposition of C3c in glomerular capillaries and simultaneous intravascular accumulation of macrophages in allografts with immediate or early humoral rejection indicates a potentially serious condition with very poor prognosis. The clinical outcome of 45 cadaveric grafts with this phenomenon among 1960 renal allografts transplanted at our centre during 1984–1999, and the recipients of the contralateral kidneys, was retrospectively evaluated. Graft failure occurred in 44/45 grafts within 3 weeks, with graft loss in 33/45 (77%) within 4 months and 37/45 (82%) within 1 year. From the contralateral kidneys, 5/33 (15%) were lost within 1 year. In a recent series of early biopsies, we recognised that of 13 cases showing C4d positivity in peritubular capillaries but lacking C3c in glomeruli, 10/13 (77%) were still functioning after 4 months. The mean number of CD68⁺ macrophages per glomerular profile, i.e. the glomerular macrophage index, shows a significant difference between C4d⁺C3c⁻ and C4d⁺C3c⁺ cases (p<0.001). Our results indicate the existence of a clinically important subgroup of early humoral rejection with particular morphological features.