Glomerulitis and endothelial cell enlargement in C4d+ and C4d- acute rejections of renal transplant patients

Abstract

In acute rejection after renal transplant, glomerulitis is characterized by mononuclear cells in glomerular capillaries and endothelial cell enlargement. In association with C4d deposition in peritubular capillaries, glomerulitis is a feature of acute antibody-mediated rejection. Prognosis in C4d(+) rejection is poorer than in C4d(-) rejection. We measured the glomerular endothelial cell area in C4d(+) and C4d(-) acute rejections by morphometry. In 90 acute rejection biopsies, glomerulitis was present in 36 cases (group G) and absent in 54 (group G0). In biopsies without rejections and in C4d(-) biopsies of group G0, glomerular endothelial cell area was not significantly different. In C4d(-) and C4d(+) biopsies of group G, the area in inflamed glomeruli was greater than that in C4d(-) biopsies of group G0 (P < .02 and P < .006, respectively). In C4d(+) biopsies of group G0, it was, unexpectedly, greater than in C4d(-) biopsies of group G (P < .01). Circulating posttransplant anti-human leukocyte antigen class I and class II antibodies correlated with increased endothelial cell area (P < .02). Glomerulitis was associated with diffuse C4d deposition (odds ratio [OR], 4.27; P < .004); C4d deposition was associated with steroid resistance (OR, 4.97; P < .002). Only in C4d(+) rejections did the presence of glomerulitis increase this association (OR, 9.17; P < .02). In conclusion, we quantified an increase of endothelial cell area in glomerulitis of C4d(+) and C4d(-) acute rejections (group G). An increase of this area in C4d(+) biopsies without glomerulitis (group G0) suggests complement-mediated damage in the absence of mononuclear cell margination.