Microcirculation Inflammation Associates With Outcome in Renal Transplant Patients With De Novo Donor-Specific Antibodies

Kort, Hanneke de; Willicombe, Michelle; Brookes, Paul; Dominy, Kathy; Santos‐Nunez, Eva; Galliford, Jack; Chan, Kakit; Taube, David; McLean, A.G.; Cook, H. Terence; Roufosse, Candice

doi:10.1111/j.1600-6143.2012.04325.x

Cited by 96 publications

(63 citation statements)

References 25 publications

(33 reference statements)

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“…Notably, in these initial studies, the worst outcome results were reported for C4d+ allografts, suggesting that C4d could indicate a more severe form of ABMR (8,31). However, this concept was questioned by subsequent reports suggesting a strong independent clinical effect of microcirculation injury (11,32,33). Nevertheless, comparably small sample sizes in many of the cited studies may have impeded the strength of multivariable statistical models.…”

Section: Discussionmentioning

confidence: 88%

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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Section: Discussionmentioning

confidence: 88%

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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“…In renal transplantation, peritubular endothelial damage, in particular endothelial C4d staining, reflects rejection (213). Endothelial inflammation is a crucial component of rejection in renal transplants and predicts graft outcomes (214,215). Experimentally, depletion of monocytes prevented capillary rarefaction (216), demonstrating the importance of interactions between inflammatory cells and the renal endothelium.…”

Section: The Role Of Interstitial Mesenchymal Cellsmentioning

confidence: 99%

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Floege

2015

American Journal of Transplantation

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“…113 Cumulative prevalence at 3 years post-transplant is similarly varied from 6% 116 to 38%, 113 with lifetime cumulative prevalence even more disparate. Class II antibodies predominate in most [115][116][117][118][119][120][121][122][123][124][125] but not all reports. [111][112][113][114] With differences in antibody MFI cutoffs, baseline immunosuppression, and frequency of testing, definitive conclusions remain elusive.…”

Section: Utility Of Hla Antibody Testing Pretransplantmentioning

confidence: 99%

Utility of HLA Antibody Testing in Kidney Transplantation

Konvalinka¹,

Tinckam

2015

Journal of the American Society of Nephrology

157

135

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HLA antigens are polymorphic proteins expressed on donor kidney allograft endothelium and are critical targets for recipient immune recognition. HLA antibodies are risk factors for acute and chronic rejection and allograft loss. Solid-phase immunoassays for HLA antibody detection represent a major advance in sensitivity and specificity over cell-based methods and are widely used in organ allocation and pretransplant risk assessment. Post-transplant, development of de novo donorspecific HLA antibodies and/or increase in donor-specific antibodies from pretransplant levels are associated with adverse outcomes. Although single antigen bead assays have allowed sensitive detection of recipient HLA antibodies and their specificities, a number of interpretive considerations must be appreciated to understand test results in clinical and research contexts. This review, which is especially relevant for clinicians caring for transplant patients, discusses the technical aspects of single antigen bead assays, emphasizes their quantitative limitations, and explores the utility of HLA antibody testing in identifying and managing important pre-and post-transplant clinical outcomes.

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Microcirculation Inflammation Associates With Outcome in Renal Transplant Patients With De Novo Donor-Specific Antibodies

Cited by 96 publications

References 25 publications

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

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

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Utility of HLA Antibody Testing in Kidney Transplantation

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