title: Significance of C4d Banff scores in early protocol biopsies of kidney transplant recipients with preformed donor-specific antibodies (DSA).
abstract: The significance of C4d-Banff scores in protocol biopsies of kidney transplant recipients with preformed donor-specific antibodies (DSA) has not been determined. We reviewed 157 protocol biopsies from 80 DSA+ patients obtained at 3 months and 1 year post-transplant. The C4d Banff scores (1,2,3) were associated with significant increments of microcirculation inflammation (MI) at both 3 months and 1 year post-transplant, worse transplant glomerulopathy and higher class II DSA-MFI (p < 0.01). Minimal-C4d had injury intermediate between negative and focal, while focal and diffuse-C4d had the same degree of microvascular injury. A total of 54% of patients had variation of C4d score between 3 months and 1 year post-transplant. Cumulative (3 month + 1 year) C4d scores correlated with long-term renal function worsening (p = 0.006). However, C4d staining was not a sensitive indicator of parenchymal disease, 55% of C4d-negative biopsies having evidence of concomitant MI. Multivariate analysis demonstrated that the presence of MI and class II DSA at 3 months were associated with a fourfold increased risk of progression to chronic antibody-mediated rejection independently of C4d (p < 0.05). In conclusion, the substantial fluctuation of C4d status in the first year post-transplant reflects a dynamic humoral process. However, C4d may not be a sufficiently sensitive indicator of activity, MI and DSA being more robust predictors of bad outcome.
authors.affiliation: Service de Transplantation Rénale et de Soins Intensifs, Hôpital Necker, APHP, Paris, France. alexandreloupy@gmail.com
authors.forename: A
authors.initials: A
authors.lastname: Loupy
authors.forename: G S
authors.initials: GS
authors.lastname: Hill
authors.forename: C
authors.initials: C
authors.lastname: Suberbielle
authors.forename: D
authors.initials: D
authors.lastname: Charron
authors.forename: D
authors.initials: D
authors.lastname: Anglicheau
authors.forename: J
authors.initials: J
authors.lastname: Zuber
authors.forename: M O
authors.initials: MO
authors.lastname: Timsit
authors.forename: J P
authors.initials: JP
authors.lastname: Duong
authors.forename: P
authors.initials: P
authors.lastname: Bruneval
authors.forename: Dewi
authors.initials: D
authors.lastname: Vernerey
authors.forename: J P
authors.initials: JP
authors.lastname: Empana
authors.forename: X
authors.initials: X
authors.lastname: Jouven
authors.forename: D
authors.initials: D
authors.lastname: Nochy
authors.forename: C H
authors.initials: CH
authors.lastname: Legendre
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies; D001706:Biopsy; D015935:Complement C4b / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007668:Kidney / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008833:Microcirculation / Q000276:immunology; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*
chemical_list: D000906:Antibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d