Publications
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Roufosse C, Willicombe M, Al Johani T, et al., 2018, Molecular assessment of C4d positive renal transplant biopsies without evidence of rejection, Publisher: SPRINGER, Pages: S15-S16, ISSN: 0945-6317
Roufosse C, Brah T, Troy-Barnes E, et al., 2018, The histopathological spectrum of monoclonal gammopathies of renal significance: a single centre experience, Publisher: SPRINGER, Pages: S81-S81, ISSN: 0945-6317
Holanda D, Drachenberg CB, Minervini MI, et al., 2018, Allograft Duodenal Cuff Biopsy as Surrogate in Evaluation of Pancreatic Transplant Rejection - A Multicenter Data Effort, 27th International Congress of the Transplantation-Society (TTS), Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: S447-S447, ISSN: 0041-1337
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Gueret-Wardle A, Dodd P, Lucisano G, et al., 2018, IgM HLA DSAs Do Not Alter the Outcomes of Renal Allograft Rejection., American Transplant Congress, Publisher: WILEY, Pages: 484-484, ISSN: 1600-6135
De Marvao A, Hadjiphilippou S, Escudier A, et al., 2018, A rare presentation of heart failure, World Congress on Acute Heart Failure, Publisher: Oxford University Press (OUP), Pages: 17-18, ISSN: 1388-9842
Tennekoon HD, de Biosanger J, Duncan N, et al., 2018, Granulomatous Tubulointerstitial Nephritis with Vasculitis, Winter Meeting on Epigenetics - Understanding Disease and Guiding Therapies / Joint Meeting of the Royal-Society-of-Medicine / 209th Scientific Meeting of the Pathological-Society-of-Great-Britain-and-Ireland, Publisher: WILEY, Pages: S13-S13, ISSN: 0022-3417
Haas M, Loupy A, Lefaucheur C, et al., 2018, The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials, AMERICAN JOURNAL OF TRANSPLANTATION, Vol: 18, Pages: 293-307, ISSN: 1600-6135
The kidney sessions of the 2017 Banff Conference focused on 2 areas: clinical implications of inflammation in areas of interstitial fibrosis and tubular atrophy (i‐IFTA) and its relationship to T cell–mediated rejection (TCMR), and the continued evolution of molecular diagnostics, particularly in the diagnosis of antibody‐mediated rejection (ABMR). In confirmation of previous studies, it was independently demonstrated by 2 groups that i‐IFTA is associated with reduced graft survival. Furthermore, these groups presented that i‐IFTA, particularly when involving >25% of sclerotic cortex in association with tubulitis, is often a sequela of acute TCMR in association with underimmunosuppression. The classification was thus revised to include moderate i‐IFTA plus moderate or severe tubulitis as diagnostic of chronic active TCMR. Other studies demonstrated that certain molecular classifiers improve diagnosis of ABMR beyond what is possible with histology, C4d, and detection of donor‐specific antibodies (DSAs) and that both C4d and validated molecular assays can serve as potential alternatives and/or complements to DSAs in the diagnosis of ABMR. The Banff ABMR criteria are thus updated to include these alternatives. Finally, the present report paves the way for the Banff scheme to be part of an integrative approach for defining surrogate endpoints in next‐generation clinical trials.
Turner S, Yeung KT, Moser S, et al., 2017, ULTRASOUND-GUIDED ALLOGRAFT PANCREAS BIOPSY: SAFETY AND DIAGNOSTIC USE, Publisher: WILEY, Pages: 141-141, ISSN: 0934-0874
Dominy K, Willicombe M, Al Johani T, et al., 2017, Assessment of C4d Positive Biopsies with No Histological Evidence of Inflammation Using Nanostring nCounter Technology, American Transplant Congress, Publisher: WILEY, Pages: 721-722, ISSN: 1600-6135
Gueret-Wardle A, Hassan S, Lucisano G, et al., 2017, Alemtuzumab Induction Is Associated with a Lower Incidence of BK Virus Nephropathy Compared with IL2RA Induction, American Transplant Congress, Publisher: WILEY, Pages: 481-481, ISSN: 1600-6135
Dominy K, Willicombe M, Al Johani T, et al., 2017, Validation of <i>CYP4F11</i> as a Marker of Accommodation in Biopsies from Recipients of an ABO-Incompatible Renal Transplant, American Transplant Congress, Publisher: WILEY, Pages: 451-452, ISSN: 1600-6135
Chen T, Rasch L, Al Johani T, et al., 2017, The Immunophenotype of Peritubular Capillaritis in Renal Transplant Biopsies, American Transplant Congress, Publisher: WILEY, Pages: 722-723, ISSN: 1600-6135
Beckwith H, Medjeral-Thomas N, Galliford J, et al., 2017, Mycophenolate mofetil therapy in immunoglobulin A nephropathy: histological changes after treatment, Nephrology Dialysis Transplantation, Vol: 32, Pages: i123-i128, ISSN: 0931-0509
BackgroundEndocapillary hypercellularity independently predicts renal outcome in immunoglobulin A nephropathy (IgAN). Mycophenolate mofetil (MMF) treatment is offered to patients presenting to the Imperial College Renal and Transplant Centre with IgAN and histological evidence of endocapillary hypercellularity. Clinical trials of MMF in IgAN have been inconclusive and have been limited by a lack of specific histological inclusion and exclusion criteria when recruiting patients. Evidence of histological improvement following MMF treatment would support its therapeutic use. We therefore reviewed histological changes after MMF therapy in a cohort of IgAN patients.MethodEighteen IgAN patients with native renal biopsies before and after repeated MMF treatment were identified. Patients were excluded if they had received any other immunosuppressive therapy, including corticosteroids. On the basis of the Oxford Classification of IgAN, we reviewed histological changes after MMF treatment.ResultsNine patients (50%) were male. At diagnostic renal biopsy, the median age was 35 years [interquartile range (IQR) 30–41], serum creatinine was 97 µmol/L (IQR 79–153) and urine protein creatinine ratio (UPCR) was 146 mg/mmol (IQR 98–212). The median time between biopsies was 24 months (range 9–41). Following MMF treatment, repeat biopsy demonstrated statistically significant improvement in the mean percentage of glomeruli showing endocapillary hypercellularity and cellular/fibrocellular crescents. There was no change in mesangial hypercellularity, segmental sclerosis or tubular atrophy scores. Mesangial IgA deposition was also significantly reduced. Histopathological improvement persisted after the cessation of MMF therapy, suggesting that 2 years of treatment is adequate for benefit. The median serum creatinine remained stable at 3 years follow-up at 104 µmol/L (IQR 79–147).ConclusionMMF treatment is associated with histopathological improveme
Loupy A, Haas M, Solez K, et al., 2017, The Banff 2015 Kidney Meeting Report: Current Challenges in Rejection Classification and Prospects for Adopting Molecular Pathology, AMERICAN JOURNAL OF TRANSPLANTATION, Vol: 17, Pages: 28-41, ISSN: 1600-6135
The XIII Banff meeting, held in conjunction the Canadian Society of Transplantation in Vancouver, Canada, reviewed the clinical impact of updates of C4d‐negative antibody‐mediated rejection (ABMR) from the 2013 meeting, reports from active Banff Working Groups, the relationships of donor‐specific antibody tests (anti‐HLA and non‐HLA) with transplant histopathology, and questions of molecular transplant diagnostics. The use of transcriptome gene sets, their resultant diagnostic classifiers, or common key genes to supplement the diagnosis and classification of rejection requires further consensus agreement and validation in biopsies. Newly introduced concepts include the i‐IFTA score, comprising inflammation within areas of fibrosis and atrophy and acceptance of transplant arteriolopathy within the descriptions of chronic active T cell–mediated rejection (TCMR) or chronic ABMR. The pattern of mixed TCMR and ABMR was increasingly recognized. This report also includes improved definitions of TCMR and ABMR in pancreas transplants with specification of vascular lesions and prospects for defining a vascularized composite allograft rejection classification. The goal of the Banff process is ongoing integration of advances in histologic, serologic, and molecular diagnostic techniques to produce a consensus‐based reporting system that offers precise composite scores, accurate routine diagnostics, and applicability to next‐generation clinical trials.
Moran L, Moss J, Willicombe M, et al., 2016, A comparison of ultrastructural glomerular features in biopsies from patients with de novo donor specific antibodies with surveillance biopsies, Publisher: SPRINGER, Pages: S24-S24, ISSN: 0945-6317
Moran L, Dominy K, Moss J, et al., 2016, A correlation of ultrastructuralmicrovascular features with endothelial cell transcripts in renal transplant biopsies, Publisher: SPRINGER, Pages: S11-S11, ISSN: 0945-6317
Moran L, Dominy K, Moss J, et al., 2016, A correlation of ultrastructural microvascular features with endothelial cell transcripts in renal transplant biopsies, Publisher: SPRINGER, Pages: S11-S11, ISSN: 0945-6317
Moran L, Moss J, Willicombe M, et al., 2016, A comparison of ultrastructural glomerular features in biopsies from patients with de novo donor specific antibodies with surveillance biopsies, Publisher: SPRINGER, Pages: S24-S24, ISSN: 0945-6317
Becker JU, Chang A, Nickeleit V, et al., 2016, Banff Borderline Changes Suspicious for Acute T Cell-Mediated Rejection: Where Do We Stand?, AMERICAN JOURNAL OF TRANSPLANTATION, Vol: 16, Pages: 2654-2660, ISSN: 1600-6135
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- Citations: 43
Willicombe M, Moss J, Moran L, et al., 2016, Tubuloreticular inclusions in renal allografts associate with viral infections and donor-specific antibodies, Journal of the American Society of Nephrology, Vol: 27, Pages: 2188-2195, ISSN: 1046-6673
The presence of tubuloreticular inclusions (TRIs) in native glomerular endothelial cells associates with viral infections and lupus nephritis. However, the associations of TRIs in renal transplant biopsy specimens are not known. We analyzed data from 316 patients who had a transplant biopsy with electron microscopy examination; 41 of 316 (13.0%) patients had TRIs. Patients with TRIs had significantly lower allograft survival rates (50.9%) than patients without TRIs (74.3%; P=0.03). Transplant glomerulopathy–free survival was also inferior in the TRI-positive group (57.5%) compared with the TRI-negative group (87.3%; P=0.002). Serologically, hepatitis C associated with the presence of TRIs (P=0.04) along with donor-specific antibodies (P=0.01). Furthermore, patients who were TRI positive were more likely than patients who were TRI negative to have had a previous rejection episode (P=0.02). On multivariate analysis, TRIs associated with prior rejection, viral infections, and class 1 HLA donor–specific antibodies. These results show that the presence of TRIs in renal allograft biopsy specimens associates with poor allograft outcomes and serologic evidence of viral infections and alloimmunity. The association with alloimmunity is a novel finding that warrants additional investigation.
McGuire E, Roufosse C, Cook T, et al., 2016, Biopsies for Delayed Graft Function After Alemtuzumab Induction in Kidney Transplantation: The Incidence of Early Rejection After Alemtuzumab Is Very Low but Not Negligible., American Transplant Congress, Publisher: WILEY-BLACKWELL, Pages: 453-453, ISSN: 1600-6135
Koutroutsos K, Moss J, Moran L, et al., 2016, Treatment of Post-Transplant Focal Glomerulosclerosis: The Effect on Histopathology Lesions and Podocyte Foot Process Effacement., American Transplant Congress, Publisher: WILEY-BLACKWELL, Pages: 775-775, ISSN: 1600-6135
Koutroutsos K, Charif R, Moran L, et al., 2016, Insights into the Treatment of Post-Transplant Focal Glomerulosclerosis: Experience Gained from a Concise Diagnostic and Management Protocol., American Transplant Congress, Publisher: WILEY-BLACKWELL, Pages: 343-343, ISSN: 1600-6135
Grau V, Zeuschner P, Immenschuh S, et al., 2016, Immune Complex-Type Deposits in the Fischer-344 to Lewis Rat Model of Renal Transplantation and a Subset of Human Transplant Glomerulopathy, TRANSPLANTATION, Vol: 100, Pages: 1004-1014, ISSN: 0041-1337
Connor TM, Aiello V, Griffith M, et al., 2016, The natural history of immunoglobulin M nephropathy in adults, Nephrology Dialysis Transplantation, Vol: 32, Pages: 823-829, ISSN: 1460-2385
BACKGROUND: Immunoglobulin M (IgM) nephropathy is an idiopathic glomerulonephritis characterized by diffuse mesangial deposition of IgM. IgM nephropathy has been a controversial diagnosis since it was first reported, and there are few data identifying specific pathological features that predict the risk of progression of renal disease. METHODS: We identified 57 cases of IgM nephropathy among 3220 adults undergoing renal biopsy at our institution. Biopsies had to satisfy the following three criteria to meet the definition of IgM nephropathy in this study: (i) dominant mesangial staining for IgM, (ii) mesangial deposits on electron microscopy (EM) and (iii) exclusion of systemic disease. RESULTS: The median age was 42 years and 24 patients were male. Thirty-nine per cent of patients presented with the nephrotic syndrome, 49% presented with non-nephrotic proteinuria and 39% had eGFR <60 mL/min. The median post-biopsy follow-up was 40 months and serum creatinine had doubled in 31% by 5 years. Of histological parameters, glomerular sclerosis and tubular atrophy, but not mesangial proliferation, were risk factors for renal insufficiency. Thirty-nine per cent of nephrotic patients achieved complete remission, and outcome was significantly worse in those who did not respond to treatment. Focal segmental glomerulosclerosis was diagnosed in 80% of those undergoing repeat renal biopsy, despite ongoing mesangial IgM deposition. CONCLUSIONS: We propose criteria for a consensus definition of IgM nephropathy.
de Kort H, Willicombe M, Brookes P, et al., 2016, Peritubular Capillary Basement Membrane Multilayering in Renal Allograft Biopsies of Patients With De Novo Donor-Specific Antibodies, Transplantation, Vol: 100, Pages: 889-897, ISSN: 1534-6080
Background. Severe peritubular capillary basement membrane multilayering (PTCBML) is part of the Banff definition of chronicantibody-mediated rejection. We retrospectively investigated whether assessment of the mean number of layers of basementmembrane (BM) around peritubular capillaries (PTC) can be used in a cohort of patients with de novo donor-specific antibodies(dnDSA) as an early marker to predict long-term antibody-mediated injury. Methods. This is a retrospective cohort study with151 electron microscopy samples from 54 patients with dnDSA, assessed at around 1 year after transplantation, for a mean numberof BM layers around PTC and in serial biopsies. Graft survival and time to transplant glomerulopathy (TG) development wereestimated in survival analyses. Results. We found that a mean PTCBML count greater than 2.5 layers assessed in a sample of 25PTCs around 1 year after transplantation is indicative of the development of TG in patients with dnDSA (P = 0.001). In addition, inpatients with serial biopsies available for electron microscopy analysis, we could distinguish 2 groups: patients with a meanPTCBML count of 2.5 or less on all biopsies, and patients who developed greater than 2.5 layers at any time after transplantation.The latter group reflected dnDSA patients at risk for TG development (P < 0.001). In patients with dnDSA, PTCBML score addedsignificantly to the sensitivity and specificity of prediction of TG compared with microcirculation injury score alone. Conclusions.Our results highlight the potential value of assessing the mean number of BM in PTC for early prediction of progression to chronicantibody-mediated injury
Pusey CD, Connor TM, Aiello V, et al., 2016, The natural history of IgM nephropathy in adults, Nephrology Dialysis Transplantation, ISSN: 1460-2385
Background: Immunoglobulin M (IgM) nephropathy is an idiopathic glomerulonephritis characterised by diffuse mesangial deposition of IgM. IgM nephropathy has been a controversial diagnosis since it was first reported, and there are few data identifying specific pathological features that predict risk of progression of renal disease.Methods: We identified 57 cases of IgM nephropathy among 3220 adults undergoing renal biopsy at our institution. Biopsies had to satisfy the following three criteria to meet the definition of IgM nephropathy in this study: (1) dominant mesangial staining for IgM, (2) mesangial deposits on EM, (3) exclusion of systemic disease.Results: The median age was 42 years and 24 patients were male. 39% of patients presented with the nephrotic syndrome, 49% patients presented with non-nephrotic proteinuria, and 39% had eGFR <60 ml/min. Median post-biopsy follow-up was 40 months and serum creatinine had doubled in 31% by 5 years. Of histological parameters, glomerular sclerosis and tubular atrophy, but not mesangial proliferation, were risk factors for renal insufficiency. 39% of nephrotic patients achieved complete remission, and outcome was significantly worse in those who did not respond to treatment. FSGS was diagnosed in 80% of those undergoing repeat renal biopsy, despite ongoing mesangial IgM deposition. Conclusions: We propose criteria for a consensus definition of IgM nephropathy.
Adam B, Afzali B, Dominy KM, et al., 2016, Multiplexed color-coded probe-based gene expression assessment for clinical molecular diagnostics in formalin-fixed paraffin-embedded human renal allograft tissue, CLINICAL TRANSPLANTATION, Vol: 30, Pages: 295-305, ISSN: 0902-0063
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- Citations: 53
Adam B, Afzali B, Dominy K, et al., 2015, VALIDATION OF THE NANOSTRING GENE EXPRESSION PLATFORM FOR MOLECULAR REJECTION DIAGNOSTICS IN FORMALIN-FIXED PARAFFIN-EMBEDDED HUMAN RENAL ALLOGRAFT TISSUE, Publisher: WILEY-BLACKWELL, Pages: 51-51, ISSN: 0934-0874
Dominy KM, Roufosse C, de Kort H, et al., 2015, Use of quantitative real time polymerase chain reaction to assess gene transcripts associated with antibody-mediated rejection of kidney transplants, Transplantation, Vol: 99, Pages: 1981-1988, ISSN: 0041-1337
Introduction Microarray studies have shown elevated transcript levels of endothelial and natural killer (NK) cell–associated genes during antibody-mediated rejection (AMR) of the renal allograft. This study aimed to assess the use of quantitative real-time polymerase chain reaction as an alternative to microarray analysis on a subset of these elevated genes.Methods Thirty-nine renal transplant biopsies from patients with de novo donor-specific antibodies and eighteen 1-year surveillance biopsies with no histological evidence of rejection were analyzed for expression of 11 genes previously identified as elevated in AMR.Results Expression levels of natural killer markers were correlated to microcirculation inflammation and graft outcomes to a greater extent than endothelial markers. Creating a predictive model reduced the number of gene transcripts to be assessed to 2, SH2D1b and MYBL1, resulting in 66.7% sensitivity and 89.7% specificity for graft loss.Discussion This work demonstrates that elevated gene expression levels, proposed to be associated with AMR, can be detected by established quantitative real-time polymerase chain reaction technology, making transition to the clinical setting feasible. Transcript analysis provides additional diagnostic information to the classification schema for AMR diagnosis but it remains to be determined whether significant numbers of centres will validate transcript analysis in their laboratories and put such analysis into clinical use.
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