Alloantibody Levels and Acute Humoral Rejection Early After Positive Crossmatch Kidney Transplantation

Burns, Justin M.; Cornell, Lynn D.; Perry, Dana K.; Pollinger, H. S.; Gloor, James M.; Kremers, Walter K.; Gandhi, Manish J.; Dean, Patrick G.; Stegall, Mark D.

doi:10.1111/j.1600-6143.2008.02441.x

Cited by 195 publications

(158 citation statements)

References 20 publications

(49 reference statements)

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“…25 Interestingly, the reported kinetics of HLA antibody levels in patients following kidney transplantation are remarkably similar to our observations. 26 Antibody levels in half of the donorspecific antibody-positive patients increased significantly on day 10, which led to the characteristic histological changes of acute humoral rejection. Thereafter, antibody levels decreased to baseline levels on day 28.…”

Section: Discussionmentioning

confidence: 99%

Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors

Taniguchi

Yoshihara

Maruya³

et al. 2012

Bone Marrow Transplant

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Section: Discussionmentioning

confidence: 99%

Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors

Taniguchi

Yoshihara

Maruya³

et al. 2012

Bone Marrow Transplant

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“…For C4d1 we found a trend toward a higher risk of graft loss (hazard ratio, 1.73; P=0.07). (18) 53 (34) 100 (15) ,0.001 105 (27) 55 (11) ,0.001 (22) 65 (42) 120 (18) ,0.001…”

Section: C4d Staining In Ptcs and Kidney Allograft Survivalmentioning

confidence: 99%

Capillary C4d and Kidney Allograft Outcome in Relation to Morphologic Lesions Suggestive of Antibody-Mediated Rejection

Kikić

Kainz

Kozakowski

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Recent studies highlighting a role of C4d2 antibody-mediated rejection (ABMR) have debated whether C4d staining has independent value as a rejection marker. Considering the presumed role of complement as an important effector of graft injury, this study hypothesized that capillary C4d, a footprint of antibody-triggered complement activation, indicates a particularly severe manifestation of ABMR.Design, setting, participants, & measurements This large retrospective clinicopathologic study sought to assess the clinical predictive value of C4d staining in relation to ABMR morphology. Overall, 885 renal allograft recipients who underwent transplantation between 1999 and 2006 (median duration of follow-up, 63.3 [interquartile range, 40.6-93.5] months; 206 graft losses) were included if they had had one or more indication biopsies. A total of 1976 biopsy specimens were reevaluated for capillary C4d staining (C4d data were available for 825 patients) and distinct morphologic lesions suggestive of ABMR, including glomerulitis, peritubular capillaritis, capillary microthrombi, transplant glomerulopathy, and severe intimal arteritis.Results C4d+ patients, with or without ABMR features, had worse death-censored 8-year graft survival (53% or 67%) than C4d2 patients (66% or 81%; P,0.001). In Cox regression analysis, C4d was associated with a risk of graft loss independently of baseline confounders and ABMR morphology (hazard ratio, 1.85 [95% confidence interval, 1.34 to 2.57]; P,0.001). The risk was higher than that observed for C4d2 patients, a finding that reached statistical significance in patients showing fewer than two different ABMR lesions. Moreover, in a mixed model, C4d was independently associated with a steeper decline of eGFR (slope per year, 28.2363.97 ml/min per 1.73 m 2 ; P,0.001).Conclusions These results suggest that detection of intragraft complement activation has strong independent value as an additional indicator of ABMR associated with adverse kidney transplant outcomes.

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“…AMR was observed only in patients with strong pretransplant DSAs (MFI values Ͼ6000) and the addition of PP to decrease the strength of DSAs significantly decreased the AMR rate to 7% from 44%. A Mayo Clinic group stratified the cross-match-positive patients into three groups per strength of DSAs: group I, with a very high level of positive cross-match (CDC T cell cross-match positive); group II, with a high level of positive cross-match (mean flow cytometry cross-match channel shift [MCS] Ͼ 300 and MESF Ͼ 19,300 units); and group III, with a low level of positive cross-match (MCS shift Ͻ 300 and MESF Ͻ 19,300 units) (52,57). They showed strong association between development of AMR and graft failure and the strength of DSAs, although AMR was still observed in patients with low-titer DSAs.…”

Section: Current Problems In Desensitization Protocolsmentioning

confidence: 99%

Desensitization Protocols and Their Outcome

Marfo

Ling

et al. 2011

Clinical Journal of the American Society of Nephrology

233

184

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SummaryIn the last decade, transplantation across previously incompatible barriers has increasingly become popular because of organ donor shortage, availability of better methods of detecting and characterizing anti-HLA antibodies, ease of diagnosis, better understanding of antibody-mediated rejection, and the availability of effective regimens. This review summarizes all manuscripts published since the first publication in 2000 on desensitized patients and discusses clinical outcomes including acute and chronic antibody-mediated rejection rate, the new agents available, kidney paired exchange programs, and the future directions in sensitized patients. There were 21 studies published between 2000 and 2010, involving 725 patients with donor-specific anti-HLA antibodies (DSAs) who underwent kidney transplantation with different desensitization protocols. All studies were single center and retrospective. The patient and graft survival were 95% and 86%, respectively, at a 2-year median follow-up. Despite acceptable short-term patient and graft survivals, acute rejection rate was 36% and acute antibody-mediated rejection rate was 28%, which is significantly higher than in nonsensitized patients. Recent studies with longer follow-up of those patients raised concerns about long-term success of desensitization protocols. The studies utilizing protocol biopsies in desensitized patients also reported higher subclinical and chronic antibody-mediated rejection. An association between the strength of DSAs determined by median fluorescence intensity values of Luminex single-antigen beads and risk of rejection was observed. Two new agents, bortezomib, a proteasome inhibitor, and eculizumab, an anti-complement C5 antibody, were recently introduced to desensitization protocols. An alternative intervention is kidney paired exchange, which should be considered first for sensitized patients.

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Alloantibody Levels and Acute Humoral Rejection Early After Positive Crossmatch Kidney Transplantation

Cited by 195 publications

References 20 publications

Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors

Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors

Capillary C4d and Kidney Allograft Outcome in Relation to Morphologic Lesions Suggestive of Antibody-Mediated Rejection

Desensitization Protocols and Their Outcome

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