Combination of peritubular c4d and transplant glomerulopathy predicts late renal allograft failure.
The histologic associations and clinical implications of peritubular capillary C4d staining from long-term renal allografts are unknown. We identified 99 renal transplant patients who underwent an allograft biopsy for renal dysfunction at least 10 yr after transplantation, 25 of whom were C4d-positive and 74 of whom were C4d-negative. The average time of the index biopsy from transplantation was 14 yr in both groups. Compared with C4d-negative patients, C4d-positive patients were younger at transplantation (29 +/- 13 versus 38 +/- 12 yr; P < 0.05) and were more likely to have received an allograft from a living donor (65 versus 35%; P < 0.001). C4d-positive patients had more inflammation, were more likely to have transplant glomerulopathy, and had worse graft outcome. The combined presence of C4d positivity, transplant glomerulopathy, and serum creatinine of >2.3 mg/dl at biopsy were very strong predictors of rapid graft loss. C4d alone did not independently predict graft loss. Retrospective staining of historical samples from C4d-positive patients demonstrated C4d deposition in the majority of cases. In summary, these data show that in long-term renal allografts, peritubular capillary staining for C4d occurs in approximately 25% of biopsies, can persist for many years after transplantation, and strongly predicts graft loss when combined with transplant glomerulopathy.
Kieran
Niamh
N
Department of Medicine, Division of Nephrology,University of Washington, Seattle, Washington 98195-6521, USA. niamh70@u.washington.edu
Wang
Xiaotong
X
Perkins
James
J
Davis
Connie
C
Kendrick
Elizabeth
E
Bakthavatsalam
Ramaswamy
R
Dunbar
Nancy
N
Warner
Paul
P
Nelson
Karen
K
Smith
Kelly D
KD
Nicosia
Roberto F
RF
Alpers
Charles E
CE
Leca
Nicolae
N
Kowalewska
Jolanta
J
D000328:Adult; D001706:Biopsy; D015935:Complement C4b / Q000032:analysis*; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology*; D007678:Kidney Glomerulus / Q000473:pathology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis*; D016016:Proportional Hazards Models; D014184:Transplantation, Homologous
D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d