title: Subclinical acute antibody-mediated rejection in positive crossmatch renal allografts.
abstract: Subclinical antibody-mediated rejection (AMR) has been described in renal allograft recipients with stable serum creatinine (SCr), however whether this leads to development of chronic allograft nephropathy (CAN) remains unknown. We retrospectively reviewed data from 83 patients who received HLA-incompatible renal allografts following desensitization to remove donor-specific antibodies (DSA). Ten patients had an allograft biopsy showing subclinical AMR [stable SCr, neutrophil margination in peritubular capillaries (PTC), diffuse PTC C4d, positive DSA] during the first year post-transplantation; 3 patients were treated with plasmapheresis and intravenous immunoglobulin. Three patients had a subsequent rise in SCr and an associated biopsy with AMR; 5 others showed diagnostic or possible subclinical AMR on a later protocol biopsy. One graft was lost, while remaining patients have normal or mildly elevated SCr 8-45 months post-transplantation. However, the mean increase in CAN score (cg + ci + ct + cv) from those biopsies showing subclinical AMR to follow-up biopsies 335 +/- 248 (SD) days later was significantly greater (3.5 +/- 2.5 versus 1.0 +/- 2.0, p = 0.01) than that in 24 recipients of HLA-incompatible grafts with no AMR over a similar interval (360 +/- 117 days), suggesting that subclinical AMR may contribute to development of CAN.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. mhaas@jhmi.edu
authors.forename: M
authors.initials: M
authors.lastname: Haas
authors.forename: R A
authors.initials: RA
authors.lastname: Montgomery
authors.forename: D L
authors.initials: DL
authors.lastname: Segev
authors.forename: M H
authors.initials: MH
authors.lastname: Rahman
authors.forename: L C
authors.initials: LC
authors.lastname: Racusen
authors.forename: S M
authors.initials: SM
authors.lastname: Bagnasco
authors.forename: C E
authors.initials: CE
authors.lastname: Simpkins
authors.forename: D S
authors.initials: DS
authors.lastname: Warren
authors.forename: D
authors.initials: D
authors.lastname: Lepley
authors.forename: A A
authors.initials: AA
authors.lastname: Zachary
authors.forename: E S
authors.initials: ES
authors.lastname: Kraus
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D000906:Antibodies / Q000276:immunology*; D015935:Complement C4b / Q000032:analysis; D003404:Creatinine / Q000097:blood; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology*; D006648:Histocompatibility; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D051437:Renal Insufficiency / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous; D044465:White People
chemical_list: D000906:Antibodies; D015234:HLA-A Antigens; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d; D003404:Creatinine