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Summary: While the detrimental impact of the humoral acute vascular rejection (AVR) phenotype is recognized, the prognostic significance of isolated v‐lesion (IV) remains unclear. In this retrospective single‐centre study, AVR was found in 98 of 1015 patients (9.7%) who had undergone kidney transplantation in 2010–2014, with donor‐specific antibodies (DSA) evaluated in all of them. The outcome of four AVR phenotypes was evaluated during median follow‐up of 59 months; in 25 patients with IV, 18 with T‐cell‐mediated vascular rejection (TCMVR), 19 with antibody‐mediated vascular rejection (AMVR) and 36 with suspected antibody‐mediated rejection (sAMVR). AVR was diagnosed mainly by for‐cause biopsy (81%) early after transplantation (median 19 POD) and appeared as mild‐grade intimal arteritis. IV occurred in low‐sensitized patients after the first transplantation (96%) in the absence of DSA. IV responded satisfactorily to treatment (88%), showed no persistence of rejection in surveillance biopsy, and had stable graft function, minimal proteinuria and excellent DCGS (96%). Contrary to that, Kaplan–Meier estimate of 3‐year DCGS of AMVR was 66% (log‐rank = 0.0004). Early IV represents a benign phenotype of AVR with a favourable outcome. This study prompts further research to evaluate the nature of IV before considering any change in the classification and management. [ABSTRACT FROM AUTHOR]

The pathological classification of rejection in renal allografts ( Banff classification) has undergone substantial evolution for more than 20 years, and has been the diagnostic gold standard in clinical practice. The 2013 updated Banff classification encompasses a revised scheme of antibody-mediated rejection ( ABMR) that consists of donor-specific antibody ( DSA) positivity, characteristic histological manifestations for both acute and chronic ABMR, and DSA-induced endothelial cell injury which is represented by either C4d positivity, microvascular inflammation or expression of activated endothelial gene transcripts. Other modified criteria include a C4d positivity threshold, and histological definition of transplant glomerulitis and transplant glomerulopathy. Morphologically, glomerulonephritis, either recurrent or de novo, can be challenging to differentiate from ABMR-mediated transplant glomerulitis. Endothelial arteritis by itself does not warrant the diagnosis of acute T-cell mediated rejection; ABMR should also be considered based on the DSA test results. With regard to polyomavirus BK-associated nephropathy, immunohistochemical examination using anti-simian virus ( SV) 40 antibody can be a promising method to assess the quantitative viral load of polyomavirus BK and graft survival. In summary, the 2013 updated Banff classification strictly defines ABMR with histopathological and serological criteria irrespective of C4d positivity. Inclusion of gene expression data relevant to ABMR highlights that the Banff criteria have entered the era of 'Seeing the Unseen' schemes, reflecting recent advances in understanding the molecular events in allograft injury. [ABSTRACT FROM AUTHOR]

Histopathological changes of acute vascular rejection ( AVR) are characterized by intimal arteritis and transmural arteritis. According to the Banff 1997 classification, the quantitative criteria for intimal arteritis (v score) are classified: v0, v1, v2, and v3. According to Banff '09 classification, AVR may fall into one of four categories: acute T cell-mediated rejection ( ATMR) Type IIA, ATMR Type IIB, ATMR Type III, and acute antibody-mediated rejection ( AAMR) Type III. Both cellular and humoral immunity play roles in vascular rejection, and in some cases, AVR may be provoked by anti-donor antibodies. Anti-rejection therapies were effective in most of the v1 cases but were less effective in the v2 cases and were ineffective in the v3 cases. Some reports have indicated that the prognosis of grafts exhibiting AVR is poor, but in our series, the outcome of AVR was relatively good using recent immunosuppressive protocols. A definition for 'isolated v-lesion' was originally characterized by arteritis with minimal interstitial inflammation and tubulitis. The 11th Banff conference was concluded that 'isolated v1-lesions' comprised two types, T cell-mediated rejection and injury, and did not have any independent prognostic significance. However, we speculate that 'isolated v-lesion' might be regarded as AAMR and ATMR. [ABSTRACT FROM AUTHOR]

Intimal arteritis is known to be a negative prognostic factor for kidney allograft survival. Isolated v-lesion (IV) is defined as intimal arteritis with minimal tubulointerstitial inflammation (TI). Although the Banff classification assesses IV as T cell-mediated rejection (TCMR), clinical, and prognostic significance of early IV (early IV, eIV) with negative C4d and donor-specific antibodies (DSA) remains unclear. To help resolve if such eIV truly represents acute rejection, a molecular study was performed. The transcriptome of eIV ( n =6), T cell-mediated vascular rejection with rich TI (T cell-mediated vascular rejection, TCMRV, n =4) and non-rejection histologic findings ( n =8) was compared using microarrays. A total of 310 genes were identified to be deregulated in TCMRV compared with eIV. Gene enrichment analysis categorized deregulated genes to be associated primarily with T-cells associated biological processes involved in an innate and adaptive immune and inflammatory response. Comparison of deregulated gene lists between the study groups and controls showed only a 1.7% gene overlap. Unsupervised hierarchical cluster analysis revealed clear distinction of eIV from TCMRV and showed similarity with a control group. Up-regulation of immune response genes in TCMRV was validated using RT-qPCR in a different set of eIV ( n =12) and TCMRV ( n =8) samples. The transcriptome of early IV (< 1 month) with negative C4d and DSA is associated with a weak immune signature compared with TCMRV and shows similarity with normal findings. Such eIV may feature non-rejection origin and reflect an injury distinct from an alloimmune response. The present study supports use of molecular methods when interpreting kidney allograft biopsy findings., (© 2018 The Author(s).)