C4d staining in post-reperfusion renal biopsy is not useful for the early detection of antibody-mediated rejection when CDC crossmatching is negative

David‐Neto, Elias; David, Débora Leite; Ginani, G F.; Rodrigues, H.; Souza, Paulo Sérgio Lopes de; Castro, Maria Cristina Ribeiro de; Kanashiro, Hideki; Saito, Fernando; Falci, Renato; Antonopoulos, Ioannis; Piovesan, Affonso; Nahas, William C.

doi:10.1093/ndt/gfq549

Cited by 9 publications

(7 citation statements)

References 17 publications

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“…The authors concluded that C4d staining in peritubular capillaries might be seen as early as one hour after transplantation in some recipients with low levels of DSA 20 . In a more recent study, 14 patients with antibody-mediated rejection had negative C4d staining in post-reperfusion biopsies 21 . It is likely that these patients were not as sensitized as those in our or the Haas study.…”

Section: Discussionmentioning

confidence: 93%

Increased C4d in post-reperfusion biopsies and increased donor specific antibodies at one-week post transplant are risk factors for acute rejection in mild to moderately sensitized kidney transplant recipients

Djamali

Muth

Ellis

et al. 2013

Kidney International

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In order to define the intensity of immunosuppression, we examined risk factors for acute rejection in desensitization protocols that use baseline donor specific antibody levels measured as mean fluorescence intensity (MFImax). The study included 146 patients transplanted with a negative flow crossmatch and a mean follow-up of 18 months with the majority (83%) followed for at least 1 year. At the time of transplant, mean calculated panel reactive antibody and MFImax ranged from 10.3% to 57.2%, and 262 to 1691, respectively, between low and high-risk protocols. Mean MFImax increased significantly from transplant to one-week and one-year. The incidence of acute rejection (mean 1.65 months) as a combination of clinical and subclinical rejection was 32% including 14% cellular, 12% antibody-mediated and 6% mixed rejection. In regression analyses, only C4d staining in post-reperfusion biopsies (hazard ratio 3.3, confidence interval 1.71 to 6.45) and increased donor specific antibodies at 1 week post-transplant were significant predictors of rejection. A rise in MFImax by 500 was associated with a 2.8-fold risk of rejection. Thus, C4d staining in post-reperfusion biopsies and an early rise in donor specific antibodies after transplantation are risk factors for rejection in moderately sensitized patients.

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Section: Discussionmentioning

confidence: 93%

Increased C4d in post-reperfusion biopsies and increased donor specific antibodies at one-week post transplant are risk factors for acute rejection in mild to moderately sensitized kidney transplant recipients

Djamali

Muth

Ellis

et al. 2013

Kidney International

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“…In addition to a standard histopathology core, another core was collected for gene expression studies. 25 Diagnosis was done first by a local pathologist and the reports were reviewed by CV and DRS to make final phenotypic assignments (discovery) and by a site-specific local pathologist and a central TGCG pathologist (validation). 24 C4d staining was performed by IF.…”

Section: Histological Analysismentioning

confidence: 99%

“…24 C4d staining was performed by IF. 25 Diagnosis was done first by a local pathologist and the reports were reviewed by CV and DRS to make final phenotypic assignments (discovery) and by a site-specific local pathologist and a central TGCG pathologist (validation). Both assessments (local and central) were performed blinded to the microarray results.…”

Section: Histological Analysismentioning

confidence: 99%

Discovery and cross-validation of peripheral blood and renal biopsy gene expression signatures from ethnically diverse kidney transplant populations

Ventura

Whisenant

David

et al. 2019

American Journal of Transplantation

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We determined peripheral blood (PB) and biopsy (Bx) RNA expression signatures in a Brazilian and US cohort of kidney transplant patients. Phenotypes assigned by precise histology were: acute rejection (AR), interstitial fibrosis/tubular atrophy/chronic rejection (CR), excellent functioning transplants (TX), and glomerulonephritis recurrence (GN). Samples were analyzed on microarrays and profiles from each cohort were cross‐validated on the other cohort with similar phenotypes. We discovered signatures for each tissue: (1) AR vs TX, (2) CR vs TX, and (3) GN vs TX using the Random Forests algorithm. We validated biopsies signatures of AR vs TX (area under the curve [AUC] 0.97) and CR vs TX (AUC 0.87). We also validated both PB and Bx signatures of AR vs TX and CR vs TX with varying degrees of accuracy. Several biological pathways were shared between AR and CR, suggesting similar rejection mechanisms in these 2 clinical phenotypes. Thus, we identified gene expression signatures for AR and CR in transplant patients and validated them in independent cohorts of significantly different racial/ethnic backgrounds. These results reveal that there are strong unifying immune mechanisms driving transplant diseases and identified in the signatures discovered in each cohort, suggesting that molecular diagnostics across populations are feasible despite ethnic and environmental differences.

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“…For example, C4d staining in post-reperfusion renal biopsy is not useful for the early detection of AMR when CDC crossmatching is negative (David-Neto et al, 2010). In ABO-incompatible transplant cases, AMR is difficult to be diagnosed by C4d analysis.…”

Section: Suspicious For Amrmentioning

confidence: 99%

Antibody-Mediated Kidney Allograft Rejection

Xu¹,

He²

2011

After the Kidney Transplant - The Patients and Their Allograft

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C4d staining in post-reperfusion renal biopsy is not useful for the early detection of antibody-mediated rejection when CDC crossmatching is negative

Abstract: These data show that C4d staining in 1-h Bx is, in general, not useful for the early detection of AMR when CDC-XM is negative.

Cited by 9 publications

References 17 publications

Increased C4d in post-reperfusion biopsies and increased donor specific antibodies at one-week post transplant are risk factors for acute rejection in mild to moderately sensitized kidney transplant recipients

Increased C4d in post-reperfusion biopsies and increased donor specific antibodies at one-week post transplant are risk factors for acute rejection in mild to moderately sensitized kidney transplant recipients

Discovery and cross-validation of peripheral blood and renal biopsy gene expression signatures from ethnically diverse kidney transplant populations

Antibody-Mediated Kidney Allograft Rejection

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