Journal
TRANSPLANTATION
Volume 89, Issue 9, Pages 1088-1094Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0b013e3181d368f1
Keywords
Acute rejection; Anti-HLA antibodies; Humoral rejection; Capillaritis; C4d
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Funding
- Nephrology and Hypertension Division of the Mayo Clinic, Rochester
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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.
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