title: Significance and implications of capillaritis during acute rejection of kidney allografts.
abstract: BACKGROUND.: Anti-human leukocyte antigen antibodies (a-HLA) cause graft injury identified by C4d in peritubular capillaries. We investigated whether a-HLA relate to episodes of C4d negative acute rejection (AR). METHODS.: We analyzed 878 kidney recipients transplanted from January 2000 to December 2006. Pretransplant, 36% of these crossmatch negative recipients had a-HLA measured by solid phase assays. RESULTS.: AR occurred in 154 patients (18%) and 11 of them (9.4%) were C4d+. Forty-six percent of ARs were diagnosed by protocol biopsy. The risk of C4d-AR was increased in patients with a-HLA class I with donor specificity (DSA-I) (hazard ratio=1.519; confidence interval, 1.02-2.26; P=0.039). DSA-II were not associated with an increased risk of C4d-AR. The relationship between DSA-I and C4d-AR was independent of recipient age, BK nephropathy, and HLA mismatches. Compared with DSA-, in DSA+ recipients C4d-AR were most often histologically "borderline." DSA+ was associated with capillaritis in the biopsy (glomerulitis, 6.1% vs. 32%, P=0.003; peritubular capillaritis: 13% vs. 40%, P=0.0009). Compared with no AR, C4d-AR with capillaritis was associated with reduced graft survival (hazard ratio=4.164; confidence interval, 1.763-9.832; P=0.001), independent of other variables. This association was observed even in the cases of borderline AR. CONCLUSIONS.: DSA-I increases the risk of C4d-AR. The presence of DSA-I or II is associated with capillaritis during AR. Capillaritis is associated with reduced graft survival.
authors.affiliation: Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA. Cosio.Fernando@mayo.edu
authors.forename: Fernando G
authors.initials: FG
authors.lastname: Cosio
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Lager
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Lorenz
authors.forename: Hatem
authors.initials: H
authors.lastname: Amer
authors.forename: James M
authors.initials: JM
authors.lastname: Gloor
authors.forename: Mark D
authors.initials: MD
authors.lastname: Stegall
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D002102:Cadaver; D002196:Capillaries / Q000276:immunology / Q000473:pathology*; D015935:Complement C4b / Q000032:analysis*; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006680:HLA Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D019520:Living Donors; D008297:Male; D010446:Peptide Fragments / Q000032:analysis*; D017741:Survivors; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d