SummaryBackground and objectives This study characterizes the pathologic and clinical relationships of thrombotic microangiopathy (TMA) to antibody-mediated rejection (AMR) in renal allograft biopsies.Design, setting, participants, & measurements Consecutive renal allograft biopsies, routinely stained for C4d over a period of 51 months (n ϭ 1101), were reviewed. For comparative analysis of histology and clinical features, additional patients with TMA and peritubular capillary (PTC) C4d (n ϭ 5) were combined with those identified in the 51-month period of review (n ϭ 6).Results One hundred eighty-two of 1073 adequate biopsies from 563 allografts had PTC C4d in the study period. Six of 37 biopsies with TMA had PTC C4d (five at Յ90 days and one at 213 days). Early (Յ90 days) C4dϩ biopsies (n ϭ 5) had more frequent TMA (11.9% C4dϩ versus 3.4% C4dϪ; odds ratio, 3.84; P ϭ 0.03). Graft loss was significantly greater in an early C4dϩTMAϩ group (n ϭ 5 study ϩ 2 archival patients) than in C4dϩ controls without TMA (n ϭ 21) (57% versus 9.5%; P ϭ 0.02). Early TMAϩC4dϩ biopsies had more severe glomerulopathy and less severe arteriolopathy than TMAϩC4dϪ and had more frequent neutrophilic capillaritis than TMAϪC4dϩ biopsies.Conclusions TMA was infrequent in this series of unselected, consecutive, renal allograft biopsies (3.4%). PTC C4d may be a significant risk factor for early TMA, and TMA is associated with glomerular thrombi and neutrophilic capillaritis. TMA in allografts with suspected AMR may portend a higher risk of graft loss.
Background. Reduction in donor-specific antibody (DSA) has been associated with improved renal allograft survival after antibody-mediated rejection (AMR). These observations have not been separately analyzed for early and late AMR and mixed acute rejection (MAR). The purpose of this study was to evaluate long-term responses to proteasome inhibitor–based therapy for 4 rejection phenotypes and to determine factors that predict allograft survival. Methods. Retrospective cohort study evaluating renal transplant recipients with first AMR episodes treated with proteasome inhibitor–based therapy from January 2005 to July 2015. Results. A total of 108 patients were included in the analysis. Immunodominant DSA reduction at 14 days differed significantly (early AMR 79.6%, early MAR 54.7%, late AMR 23.4%, late MAR 21.1%, P < 0.001). Death-censored graft survival (DCGS) differed at 3 years postrejection (early AMR 88.3% versus early MAR 77.8% versus late AMR 56.7% versus late MAR 54.9%, P = 0.02). Multivariate analysis revealed that immunodominant DSA reduction > 50% at 14 days was associated with improved DCGS (odds ratio, 0.12, 95% CI, 0.02-0.52, P = 0.01). Conclusions. In summary, significant differences exist across rejection phenotypes with respect to histological and DSA responses. The data suggest that DSA reduction may be associated with improved DCGS in both early and late AMR.
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