Michael Mengel

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..This review summarizes the current diagnostic consensus for ABMR, describes unmet needs and challenges in diagnostics, and proposes new approaches for consideration...

..Results are expected to be presented at the 12th Banff meeting to be held in 2013 in Brazil. No change to the Banff classification occurred in 2011...

..The purpose of this review is to summarize new diagnostic insights into the identification of specific causes of late allograft failure...

..Thus, the total i-score is superior to the current Banff i-score and most diagnostic Banff categories in predicting outcome and assessing the molecular phenotype of renal allografts...

..Thus while detecting T cell-mediated inflammation, the molecular phenotype of early protocol biopsies mostly reflects the injury-repair response to implantation stresses, and has little relationship to future events and outcomes...

..The threat is the degree to which the renal transplant community will participate in and support this process...

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..In an independent validation set, the molecular risk score was the only predictor of graft loss. Thus, the molecular risk score reflects active injury and is superior to either scarring or function in predicting graft failure...

..g., accessibility via internet, no fading. We recommend virtual microscopy for transplant diagnostics, including utilization for clinical trials...

..Thus, in biopsies performed for clinical reasons, functional disturbances are reflected in transcriptome changes representing tissue injury and dedifferentiation but not the inflammatory burden...

..Thus, the strategy of using DSASTs in the biopsy to identify mechanism-related transcripts in biopsies from patients with clinical phenotypes indicates the selective involvement of NK cells in ABMR...

..Interpretation of lesions should reflect these associations...

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..PBTs represent a quantitative measure of the inflammatory disturbances in organ transplants, and a new window on the mechanisms of these changes...

..The major cause of late kidney transplant failure is antibody-mediated microcirculation injury, but detection of this phenotype requires new diagnostic criteria...

..We propose careful assessment of de novo DSA, particularly against class II, be performed in all late kidney transplant biopsies...

..Expression of BATs and IGTs correlated with renal function, but this relationship was due to differences in early versus late biopsies: BATs and IGTs were not related to function or future function after correcting for time...

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..Participation of B cells in allograft rejection and genomics markers of rejection were also major subjects addressed by the conference...

..Thus the molecular phenotype is best described in terms of three elements: specific diseases, including rejection; the injury-repair response and the cumulative burden of injury...

..03) but not with clinical or histopathologic scores. The transcriptome reflects kidney quality and susceptibility to DGF better than available clinical and histopathological scoring systems...

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..The active injury-repair response is the strongest correlate of organ function and future progression to failure, but should always prompt a search for the initiating injury or disease...

..Scarring is associated with a distinct pattern of inflammatory molecules, including B cell/immunoglobulin but particularly mast cell-associated transcripts, which correlated with poor outcomes...

..The dynamic range of both platforms was sufficient to detect the relevant changes in rejection...

..Thus, in renal allografts, allorecognition by T cells occurs in perivascular sites by day 1, but alloimmune parenchymal damage begins at day 3, coinciding with the emergence of the interstitial T-cell-MMDC infiltrate...

..We propose that in TCMR, interstitial effector T cells mediate parenchymal injury by inflammatory mechanisms that require neither the perforin-granzyme nor the Fas-Fas ligand cytotoxic mechanisms...

..Thus QCAT sets robustly measure the burden of CTL and effector memory T cells in biopsies as %CTL RNA, in a manner not achieved by measurement of individual transcripts...

..Thus FOXP3 mRNA expression is a time-dependent feature of inflammatory infiltrates in renal tissue. We hypothesize that time-dependent entry of FOXP3-positive cells represents a mechanism for stabilizing inflammatory sites...

..The alloresponse strikingly and selectively increased the late IRITs but not the IRITs that peak early, indicating that rejection triggers parenchymal responses similar to those in ATN...

..This combination of pathologic, clinical and molecular features constitutes the typical or canonical T-cell-mediated rejection...

..Single dose rituximab may effectively reverse even long-lasting refractory rejection...

..Thus, we think that caution is required, particularly in connection with preexisting glomerular disease...

..Wider application is expected in multicenter clinical trials to predict and validate outcomes. The principal barrier to wider use of protocol biopsies is knowledge of the benefits of intervention...

..As detected by sequential biopsies, persistence of any inflammation including those infiltrates currently not considered by the Banff classification should be regarded as a morphological correlate of ongoing allograft damage...

..0001). Capillaritis is more frequent and pronounced in ABMR, but can be observed in TCMR cases. Thus, scoring of peritubular capillaritis is feasible and can provide prognostic and diagnostic information in renal allograft biopsies...

..Better understanding of early onset of interstitial fibrosis and tubular atrophy (IF/TA), as the morphological surrogate of renal allograft deterioration might improve outcome after renal transplantation...

..In conclusion, lymphangiogenesis not only shows a clear association with cellular infiltrates but might also have an impact on the pathogenicity of these cellular infiltrates...

..There was no evidence of recurrence or metastasis of the primary leiomyosarcoma of the pulmonary artery in a 14-month follow-up period after operation...

..Chronic renal failure in PNH is a diagnosis of exclusion, even if radiologic evidence of heavy siderosis draws off the physician's attention...

..Therefore, in the present investigation the expression within different tissue areas obtained from renal cell carcinomas was determined...

..This case demonstrates that in a child with a unilateral, progressive orbital tumor, the differential diagnosis of a soft tissue sarcoma has to be ruled out...

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..The genetic changes reported here should provide new insights into the developmental paths leading to tumour progression and may also aid the design of new approaches to therapeutic intervention...