Antibody-Mediated Microcirculation Injury Is the Major Cause of Late Kidney Transplant Failure
Bibliographic record
Abstract
To the Editor: We congratulate the authors on the recent paper entitled ‘Antibody-Mediated Microcirculation Injury Is the Major Cause of Late Kidney Transplant Failure’ (1Einecke G Sis B Reeve J et al.Antibody-mediated microcirculation injury is the major cause of late kidney transplant failure.Am J Transplant. 2009; 9: 2520-2531Abstract Full Text Full Text PDF PubMed Scopus (550) Google Scholar) published in AJT. In this study, the authors show that antibody-related microcirculation inflammation accounts in substantial part for renal transplant failure and importantly, regardless of the C4d status. This paper underlines the clinical relevance of donor specific anti-HLA antibodies (DSA)-related microcirculation changes in biopsies for cause that are C4d-negative. This situation is not subsumed under the Banff diagnostic criteria (2Solez K Colvin RB Racusen LC et al.Banff 07 classification of renal allograft pathology: Updates and future directions.Am J Transplant. 2008; 8: 753-760Crossref PubMed Scopus (1641) Google Scholar), suggesting that the current definition of antibody-mediated rejection (ABMR) emphasizing C4d staining may not be sufficiently sensitive. We have accumulated at our institution a substantial experience in performing screening biopsies (3Thaunat O Legendre C Morelon E Kreis H Mamzer-Bruneel MF To biopsy or not to biopsy? Should we screen the histology of stable renal grafts?.Transplantation. 2007; 84: 671-676Crossref PubMed Scopus (53) Google Scholar). We have recently observed in a cohort 54 kidney transplant recipients with preformed anti-HLA DSA, that 22 out of 45 patients having adequate screening biopsies at 3 months posttransplant showed asymptomatic C4d-negative microcirculation inflammation lesions (prevalence of 48.9%). This group of C4d-negative subclinical AMR at 3-month developed at 1 year a significantly higher grade of microcirculation inflammation lesions, a higher rate of transplant glomerulopathy lesions (18% vs. 0%), a higher prevalence of interstitial-fibrosis/tubular atrophy lesions (72.2% vs. 33.1% respectively, p = 0.2) as compared to biopsies without humoral lesions, leading to lower GFR at 1 year (45.9 ± 17 vs. 61.9 ± 19 mL/min/1.73m2 respectively, p < 0.01). Finally, this group of patients with C4d-negative microcirculation inflammation displayed an intermediate course between patients without humoral lesions, and patients with C4d+SAMR, with a gradation of severity for almost all morphological and immunological parameters (particularly class II DSA MFI), thus representing a milder but progressive form of antibody-mediated rejection (4Loupy A Suberbielle-Boissel C Hill GS et al.Outcome of subclinical antibody-mediated rejection in kidney transplant recipients with preformed donor-specific antibodies.Am J Transplant. 2009; 9: 2561-2570Abstract Full Text Full Text PDF PubMed Scopus (272) Google Scholar). Therefore, it would seem that the observations described by Eineke et al. could equally be extended to the spectrum of lesions seen in ‘stable’ grafts (e.g. stable or adequate GFR without change in level of proteinuria or blood pressure) biopsied in protocol fashion. The results of the Edmonton group thus underscore the fact that C4d-negative microcirculation inflammation in DSA+ patients should become a part of the criteria for subclinical AMR which, as presently defined, requires C4d-positivity (5Haas M Montgomery RA Segev DL et al.Subclinical acute antibody-mediated rejection in positive crossmatch renal allografts.Am J Transplant. 2007; 7: 576-585Crossref PubMed Scopus (121) Google Scholar). As such, this immuno-histopathological entity should be taken into account in the management of kidney transplant recipients with high immunological risk.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.024 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.003 | 0.001 |
| Research integrity | 0.007 | 0.011 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".