title: Combination of peritubular c4d and transplant glomerulopathy predicts late renal allograft failure.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Nephrology,University of Washington, Seattle, Washington 98195-6521, USA. niamh70@u.washington.edu
authors.forename: Niamh
authors.initials: N
authors.lastname: Kieran
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Wang
authors.forename: James
authors.initials: J
authors.lastname: Perkins
authors.forename: Connie
authors.initials: C
authors.lastname: Davis
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kendrick
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Bakthavatsalam
authors.forename: Nancy
authors.initials: N
authors.lastname: Dunbar
authors.forename: Paul
authors.initials: P
authors.lastname: Warner
authors.forename: Karen
authors.initials: K
authors.lastname: Nelson
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Smith
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Nicosia
authors.forename: Charles E
authors.initials: CE
authors.lastname: Alpers
authors.forename: Nicolae
authors.initials: N
authors.lastname: Leca
authors.forename: Jolanta
authors.initials: J
authors.lastname: Kowalewska
mesh_terms: 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
chemical_list: D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d