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1. Cell-free DNA for the detection of kidney allograft rejection

Author

Aubert, Olivier, Ursule-Dufait, Cindy, Brousse, Romain, Gueguen, Juliette, Racapé, Maud, Raynaud, Marc, Van Loon, Elisabet, Pagliazzi, Angelica, Huang, Edmund, Jordan, Stanley C., Chavin, Kenneth D., Gupta, Gaurav, Kumar, Dhiren, Alhamad, Tarek, Anand, Sanjiv, Sanchez-Garcia, Jorge, Abdalla, Basmah A., Hogan, Julien, Garro, Rouba, Dadhania, Darshana M., Jain, Pranjal, Mandelbrot, Didier A., Naesens, Maarten, Dandamudi, Raja, Dharnidharka, Vikas R., Anglicheau, Dany, Lefaucheur, Carmen, and Loupy, Alexandre

Published
2024
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2. Integrative multi-omics profiling in human decedents receiving pig heart xenografts

Author

Schmauch, Eloi, Piening, Brian, Mohebnasab, Maedeh, Xia, Bo, Zhu, Chenchen, Stern, Jeffrey, Zhang, Weimin, Dowdell, Alexa K., Kim, Jacqueline I., Andrijevic, David, Khalil, Karen, Jaffe, Ian S., Loza, Bao-Li, Gragert, Loren, Camellato, Brendan R., Oliveira, Michelli F., O’Brien, Darragh P., Chen, Han M., Weldon, Elaina, Gao, Hui, Gandla, Divya, Chang, Andrew, Bhatt, Riyana, Gao, Sarah, Lin, Xiangping, Reddy, Kriyana P., Kagermazova, Larisa, Habara, Alawi H., Widawsky, Sophie, Liang, Feng-Xia, Sall, Joseph, Loupy, Alexandre, Heguy, Adriana, Taylor, Sarah E. B., Zhu, Yinan, Michael, Basil, Jiang, Lihua, Jian, Ruiqi, Chong, Anita S., Fairchild, Robert L., Linna-Kuosmanen, Suvi, Kaikkonen, Minna U., Tatapudi, Vasishta, Lorber, Marc, Ayares, David, Mangiola, Massimo, Narula, Navneet, Moazami, Nader, Pass, Harvey, Herati, Ramin S., Griesemer, Adam, Kellis, Manolis, Snyder, Michael P., Montgomery, Robert A., Boeke, Jef D., and Keating, Brendan J.

Published
2024
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3. Design, cohort profile and comparison of the KTD-Innov study: a prospective multidimensional biomarker validation study in kidney allograft rejection

Author

Goutaudier, Valentin, Sablik, Marta, Racapé, Maud, Rousseau, Olivia, Audry, Benoit, Kamar, Nassim, Raynaud, Marc, Aubert, Olivier, Charreau, Béatrice, Papuchon, Emmanuelle, Danger, Richard, Letertre, Laurence, Couzi, Lionel, Morelon, Emmanuel, Le Quintrec, Moglie, Taupin, Jean-Luc, Vicaut, Eric, Legendre, Christophe, Le Mai, Hoa, Potluri, Vishnu, Nguyen, Thi-Van-Ha, Azoury, Marie-Eliane, Pinheiro, Alice, Nouadje, Georges, Sonigo, Pierre, Anglicheau, Dany, Tieken, Ineke, Vogelaar, Serge, Jacquelinet, Christian, Reese, Peter, Gourraud, Pierre-Antoine, Brouard, Sophie, Lefaucheur, Carmen, and Loupy, Alexandre

Published
2024
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4. Successful prevention of BK-polyomavirus nephropathy using extracorporeal photopheresis for immunosuppression minimisation following severe BK polyomavirus replication after kidney transplantation in a double lung transplant recipient, a case report

Author

Von Tokarski, Florent, Parquin, François, Roux, Antoine, Hayem, Victor, Kerdiles, Thibault, Rabant, Marion, Isnard, Pierre, Loupy, Alexandre, Fourniol, Cyril, Tricot, Leila, Picard, Clément, Hertig, Alexandre, and Oniszczuk, Julie

Published
2024
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5. High-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats

Author

de Noronha, Sylvana I. S. Rendeiro, de Moraes, Lauro Angelo Gonçalves, Hassell, Jr., James E., Stamper, Christopher E., Arnold, Mathew R., Heinze, Jared D., Foxx, Christine L., Lieb, Margaret M., Cler, Kristin E., Karns, Bree L., Jaekel, Sophia, Loupy, Kelsey M., Silva, Fernanda C. S., Chianca-Jr., Deoclécio Alves, Lowry, Christopher A., and de Menezes, Rodrigo Cunha

Published
2024
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6. A Machine Learning-Driven Virtual Biopsy System For Kidney Transplant Patients

Author

Yoo, Daniel, Divard, Gillian, Raynaud, Marc, Cohen, Aaron, Mone, Tom D., Rosenthal, John Thomas, Bentall, Andrew J., Stegall, Mark D., Naesens, Maarten, Zhang, Huanxi, Wang, Changxi, Gueguen, Juliette, Kamar, Nassim, Bouquegneau, Antoine, Batal, Ibrahim, Coley, Shana M., Gill, John S., Oppenheimer, Federico, De Sousa-Amorim, Erika, Kuypers, Dirk R. J., Durrbach, Antoine, Seron, Daniel, Rabant, Marion, Van Huyen, Jean-Paul Duong, Campbell, Patricia, Shojai, Soroush, Mengel, Michael, Bestard, Oriol, Basic-Jukic, Nikolina, Jurić, Ivana, Boor, Peter, Cornell, Lynn D., Alexander, Mariam P., Toby Coates, P., Legendre, Christophe, Reese, Peter P., Lefaucheur, Carmen, Aubert, Olivier, and Loupy, Alexandre

Published
2024
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7. From Humoral Theory to Performant Risk Stratification in Kidney Transplantation

Author

C. Lefaucheur, D. Viglietti, M. Mangiola, A. Loupy, and A. Zeevi

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

The purpose of the present review is to describe how we improve the model for risk stratification of transplant outcomes in kidney transplantation by incorporating the novel insights of donor-specific anti-HLA antibody (DSA) characteristics. The detection of anti-HLA DSA is widely used for the assessment of pre- and posttransplant risks of rejection and allograft loss; however, not all anti-HLA DSA carry the same risk for transplant outcomes. These antibodies have been shown to cause a wide spectrum of effects on allografts, ranging from the absence of injury to indolent or full-blown acute antibody-mediated rejection. Consequently, the presence of circulating anti-HLA DSA does not provide a sufficient level of accuracy for the risk stratification of allograft outcomes. Enhancing the predictive performance of anti-HLA DSA is currently one of the most pressing unmet needs for facilitating individualized treatment choices that may improve outcomes. Recent advancements in the assessment of anti-HLA DSA properties, including their strength, complement-binding capacity, and IgG subclass composition, significantly improved the risk stratification model to predict allograft injury and failure. Although risk stratification based on anti-HLA DSA properties appears promising, further specific studies that address immunological risk stratification in large and unselected populations are required to define the benefits and cost-effectiveness of such comprehensive assessment prior to clinical implementation.

Published
2017
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8. High-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats

Author

Sylvana I. S. Rendeiro de Noronha, Lauro Angelo Gonçalves de Moraes, James E. Hassell, Christopher E. Stamper, Mathew R. Arnold, Jared D. Heinze, Christine L. Foxx, Margaret M. Lieb, Kristin E. Cler, Bree L. Karns, Sophia Jaekel, Kelsey M. Loupy, Fernanda C. S. Silva, Deoclécio Alves Chianca-Jr., Christopher A. Lowry, and Rodrigo Cunha de Menezes

Subjects
Anxiety, Dorsal raphe nucleus, High-fat diet, Microbiome, Microbiome-gut-brain axis, Obesity, Biology (General), QH301-705.5
Abstract

Abstract Obesity, associated with the intake of a high-fat diet (HFD), and anxiety are common among those living in modern urban societies. Recent studies suggest a role of microbiome-gut-brain axis signaling, including a role for brain serotonergic systems in the relationship between HFD and anxiety. Evidence suggests the gut microbiome and the serotonergic brain system together may play an important role in this response. Here we conducted a nine-week HFD protocol in male rats, followed by an analysis of the gut microbiome diversity and community composition, brainstem serotonergic gene expression (tph2, htr1a, and slc6a4), and anxiety-related defensive behavioral responses. We show that HFD intake decreased alpha diversity and altered the community composition of the gut microbiome in association with obesity, increased brainstem tph2, htr1a and slc6a4 mRNA expression, including in the caudal part of the dorsomedial dorsal raphe nucleus (cDRD), a subregion previously associated with stress- and anxiety-related behavioral responses, and, finally, increased anxiety-related defensive behavioral responses. The HFD increased the Firmicutes/Bacteroidetes ratio relative to control diet, as well as higher relative abundances of Blautia, and decreases in Prevotella. We found that tph2, htr1a and slc6a4 mRNA expression were increased in subregions of the dorsal raphe nucleus in the HFD, relative to control diet. Specific bacterial taxa were associated with increased serotonergic gene expression in the cDRD. Thus, we propose that HFD-induced obesity is associated with altered microbiome-gut-serotonergic brain axis signaling, leading to increased anxiety-related defensive behavioral responses in rats.

Published
2024
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9. Antibody Mediated Rejection and T-cell Mediated Rejection Molecular Signatures Using Next-Generation Sequencing in Kidney Transplant Biopsies

Author

Esteban Cortes Garcia, Alessia Giarraputo, Maud Racapé, Valentin Goutaudier, Cindy Ursule-Dufait, Pierre de la Grange, Lucie Adoux, Marc Raynaud, Clément Couderau, Fariza Mezine, Jessie Dagobert, Oriol Bestard, Francesc Moreso, Jean Villard, Fabian Halleck, Magali Giral, Sophie Brouard, Richard Danger, Pierre-Antoine Gourraud, Marion Rabant, Lionel Couzi, Moglie Le Quintrec, Nassim Kamar, Emmanuel Morelon, François Vrtovsnik, Jean-Luc Taupin, Renaud Snanoudj, Christophe Legendre, Dany Anglicheau, Klemens Budde, Carmen Lefaucheur, Alexandre Loupy, and Olivier Aubert

Subjects
next generation sequencing, RNA-seq experiment, kidney biopsies, molecular signature, allograft rejection, kidney transplantation, Specialties of internal medicine, RC581-951
Abstract

Recently, interest in transcriptomic assessment of kidney biopsies has been growing. This study investigates the use of NGS to identify gene expression changes and analyse the pathways involved in rejection. An Illumina bulk RNA sequencing on the polyadenylated RNA of 770 kidney biopsies was conducted. Differentially-expressed genes (DEGs) were determined for AMR and TCMR using DESeq2. Genes were segregated according to their previous descriptions in known panels (microarray or the Banff Human Organ Transplant (B-HOT) panel) to obtain NGS-specific genes. Pathway enrichment analysis was performed using the Reactome and Kyoto Encyclopaedia of Genes and Genomes (KEGG) public repositories. The differential gene expression using NGS analysis identified 6,141 and 8,478 transcripts associated with AMR and TCMR. While most of the genes identified were included in the microarray and the B-HOT panels, NGS analysis identified 603 (9.8%) and 1,186 (14%) new specific genes. Pathways analysis showed that the B-HOT panel was associated with the main immunological processes involved during AMR and TCMR. The microarrays specifically integrated metabolic functions and cell cycle progression processes. Novel NGS-specific based transcripts associated with AMR and TCMR were discovered, which might represent a novel source of targets for drug designing and repurposing.

Published
2024
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10. The role of donor hypertension and angiotensin II in the occurrence of early pancreas allograft thrombosis

Author

Christophe Masset, Julien Branchereau, Fanny Buron, Georges Karam, Maud Rabeyrin, Karine Renaudin, Florent Le Borgne, Lionel Badet, Xavier Matillon, Christophe Legendre, Denis Glotz, Corinne Antoine, Magali Giral, Jacques Dantal, Diego Cantarovich, DIVAT Consortium, Maria Brunet, Rémi Cahen, Ricardo Codas, Sameh Daoud, Valérie Dubois, Coralie Fournie, Arnaud Grégoire, Alice Koenig, Charlène Lévi, Emmanuel Morelon, Claire Pouteil-Noble, Thomas Rimmelé, Olivier Thaunat, Gilles Blancho, Agnès Chapelet, Clément Deltombe, Lucile Figueres, Raphael Gaisne, Claire Garandeau, Caroline Gourraud-Vercel, Maryvonne Hourmant, Clarisse Kerleau, Delphine Kervella, Aurélie Meurette, Simon Ville, Christine Kandell, Anne Moreau, Florent Delbos, Alexandre Walencik, Anne Devis, Lucile Amrouche, Dany Anglicheau, Olivier Aubert, Lynda Bererhi, Alexandre Loupy, Frank Martinez, Arnaud Méjean, Rébecca Sberro-Soussan, Anne Scemla, Marc-Olivier Timsit, Julien Zuber, Gillian Divard, and Carmen Lefaucheur

Subjects
body mass index (BMI), pre-procurement pancreas suitability score, pancreas transplantation, allograft thrombosis, high blood pressure, immunothrombosis, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundAbout 10–20% of pancreas allografts are still lost in the early postoperative period despite the identification of numerous detrimental risk factors that correlate with graft thrombosis.MethodsWe conducted a multicenter study including 899 pancreas transplant recipients between 2000 and 2018. Early pancreas failure due to complete thrombosis, long-term pancreas, kidney and patient survivals were analyzed and adjusted to donor, recipient and perioperative variables using a multivariate cause-specific Cox model stratified to transplant centers.ResultsPancreas from donors with history of hypertension (6.7%), as well as with high body mass index (BMI), were independently associated with an increased risk of pancreas failure within the first 30 post-operative days (respectively, HR= 2.57, 95% CI from 1.35 to 4.89 and HR= 1.11, 95% CI from 1.04 to 1.19). Interaction term between hypertension and BMI was negative. Donor hypertension also impacted long-term pancreas survival (HR= 1.88, 95% CI from 1.13 to 3.12). However, when pancreas survival was calculated after the postoperative day 30, donor hypertension was no longer a significant risk factor (HR= 1.22, 95% CI from 0.47 to 3.15). A lower pancreas survival was observed in patients receiving a pancreas from a hypertensive donor without RAAS (Renin Angiotensin Aldosterone System) blockers compared to others (50% vs 14%, p < 0.001). Pancreas survival was similar among non-hypertensive donors and hypertensive ones under RAAS blockers.ConclusionDonor hypertension was a significant and independent risk factor of pancreas failure. The well-known pathogenic role of renin-angiotensin-aldosterone system seems to be involved in the genesis of this immediate graft failure.

Published
2024
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12. High-dimensional mass cytometry identified circulating natural killer T-cell subsets associated with protection from cytomegalovirus infection in kidney transplant recipients

Author

Donadeu, Laura, Jouve, Thomas, Bin, Sofia, Hartzell, Susan, Crespo, Elena, Torija, Alba, Jarque, Marta, Kervella, Delphine, Zúñiga, José, Zhang, Weijia, Sun, Zeguo, Verlato, Alberto, Martínez-Gallo, Mónica, Font-Miñarro, Cristina, Meneghini, Maria, Toapanta, Nestor, Torres, Irina B., Sellarés, Joana, Perelló, Manel, Kaminski, Hannah, Couzi, Lionel, Loupy, Alexandre, La Manna, Gaetano, Moreso, Francesc, Cravedi, Paolo, and Bestard, Oriol

Published
2024
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14. A Machine Learning-Driven Virtual Biopsy System For Kidney Transplant Patients

Author

Daniel Yoo, Gillian Divard, Marc Raynaud, Aaron Cohen, Tom D. Mone, John Thomas Rosenthal, Andrew J. Bentall, Mark D. Stegall, Maarten Naesens, Huanxi Zhang, Changxi Wang, Juliette Gueguen, Nassim Kamar, Antoine Bouquegneau, Ibrahim Batal, Shana M. Coley, John S. Gill, Federico Oppenheimer, Erika De Sousa-Amorim, Dirk R. J. Kuypers, Antoine Durrbach, Daniel Seron, Marion Rabant, Jean-Paul Duong Van Huyen, Patricia Campbell, Soroush Shojai, Michael Mengel, Oriol Bestard, Nikolina Basic-Jukic, Ivana Jurić, Peter Boor, Lynn D. Cornell, Mariam P. Alexander, P. Toby Coates, Christophe Legendre, Peter P. Reese, Carmen Lefaucheur, Olivier Aubert, and Alexandre Loupy

Subjects
Science
Abstract

Abstract In kidney transplantation, day-zero biopsies are used to assess organ quality and discriminate between donor-inherited lesions and those acquired post-transplantation. However, many centers do not perform such biopsies since they are invasive, costly and may delay the transplant procedure. We aim to generate a non-invasive virtual biopsy system using routinely collected donor parameters. Using 14,032 day-zero kidney biopsies from 17 international centers, we develop a virtual biopsy system. 11 basic donor parameters are used to predict four Banff kidney lesions: arteriosclerosis, arteriolar hyalinosis, interstitial fibrosis and tubular atrophy, and the percentage of renal sclerotic glomeruli. Six machine learning models are aggregated into an ensemble model. The virtual biopsy system shows good performance in the internal and external validation sets. We confirm the generalizability of the system in various scenarios. This system could assist physicians in assessing organ quality, optimizing allograft allocation together with discriminating between donor derived and acquired lesions post-transplantation.

Published
2024
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15. Evaluation of non-invasive biomarkers of kidney allograft rejection in a prospective multicenter unselected cohort study (EU-TRAIN)

Author

Goutaudier, Valentin, Danger, Richard, Catar, Rusan Ali, Racapé, Maud, Philippe, Aurélie, Elias, Michelle, Raynaud, Marc, Aubert, Olivier, Bouton, Didier, Girardin, François, Vicaut, Éric, Yaiche, Sarhan, Demotes, Jacques, Heidecke, Harald, Taupin, Jean-Luc, Randoux-Lebrun, Christine, Zaidan, Mohamad, Papuchon, Emmanuelle, Le Mai, Hoa, Nguyen, Thi-Van-Ha, Moreso, Francesc, Berney, Thierry, Villard, Jean, Legendre, Christophe, Dragun, Duska, Papalois, Vassilios, Potena, Luciano, Giral, Magali, Gourraud, Pierre-Antoine, Brouard, Sophie, Crespo, Elena, Halleck, Fabian, Budde, Klemens, Bestard, Oriol, Loupy, Alexandre, and Lefaucheur, Carmen

Published
2024
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16. Identification of liver transplant biopsy phenotypes associated with distinct liver biological markers and allograft survival

Author

Demir, Zeynep, Raynaud, Marc, Aubert, Olivier, Debray, Dominique, Sebagh, Mylène, Duong Van Huyen, Jean-Paul, Del Bello, Arnaud, Jolivet, Nicolas Congy, Paradis, Valérie, Durand, François, Muratot, Sophie, Lozach, Cécile, Chardot, Christophe, Francoz, Claire, Kamar, Nassim, Sarnacki, Sabine, Coilly, Audrey, Samuel, Didier, Vibert, Eric, Féray, Cyrille, Lefaucheur, Carmen, and Loupy, Alexandre

Published
2024
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17. An automated histological classification system for precision diagnostics of kidney allografts

Author

Yoo, Daniel, Goutaudier, Valentin, Divard, Gillian, Gueguen, Juliette, Astor, Brad C., Aubert, Olivier, Raynaud, Marc, Demir, Zeynep, Hogan, Julien, Weng, Patricia, Smith, Jodi, Garro, Rouba, Warady, Bradley A., Zahr, Rima S., Sablik, Marta, Twombley, Katherine, Couzi, Lionel, Berney, Thierry, Boyer, Olivia, Duong-Van-Huyen, Jean-Paul, Giral, Magali, Alsadi, Alaa, Gourraud, Pierre A., Morelon, Emmanuel, Le Quintrec, Moglie, Brouard, Sophie, Legendre, Christophe, Anglicheau, Dany, Villard, Jean, Zhong, Weixiong, Kamar, Nassim, Bestard, Oriol, Djamali, Arjang, Budde, Klemens, Haas, Mark, Lefaucheur, Carmen, Rabant, Marion, and Loupy, Alexandre

Published
2023
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19. The Banff 2022 Kidney Meeting Work Plan: Data-driven refinement of the Banff Classification for renal allografts

Author

Roufosse, Candice, Naesens, Maarten, Haas, Mark, Lefaucheur, Carmen, Mannon, Roslyn B., Afrouzian, Marjan, Alachkar, Nada, Aubert, Olivier, Bagnasco, Serena M., Batal, Ibrahim, Bellamy, Chris O.C., Broecker, Verena, Budde, Klemens, Clahsen-Van Groningen, Marian, Coley, Shana M., Cornell, Lynn D., Dadhania, Darshana, Demetris, Anthony J., Einecke, Gunilla, Farris, Alton B., Fogo, Agnes B., Friedewald, John, Gibson, Ian W., Horsfield, Catherine, Huang, Edmund, Husain, Syed A., Jackson, Annette M., Kers, Jesper, Kikić, Željko, Klein, Amanda, Kozakowski, Nicolas, Liapis, Helen, Mangiola, Massima, Montgomery, Robert A., Nankinvell, Brian, Neil, Desley A.H., Nickerson, Peter, Rabant, Marion, Randhawa, Parmjeet, Riella, Leonardo V., Rosales, Ivy, Royal, Virginie, Sapir-Pichhadze, Ruth, Sarder, Pinaki, Sarwal, Minnie, Schinstock, Carrie, Stegall, Mark, Solez, Kim, van der Laak, Jeroen, Wiebe, Chris, Colvin, Robert B., Loupy, Alexandre, and Mengel, Michael

Published
2024
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20. The Banff 2022 Kidney Meeting Report: Reappraisal of microvascular inflammation and the role of biopsy-based transcript diagnostics

Author

Naesens, Maarten, Roufosse, Candice, Haas, Mark, Lefaucheur, Carmen, Mannon, Roslyn B., Adam, Benjamin A., Aubert, Olivier, Böhmig, Georg A., Callemeyn, Jasper, Clahsen-van Groningen, Marian, Cornell, Lynn D., Demetris, Anthony J., Drachenberg, Cinthia B., Einecke, Gunilla, Fogo, Agnes B., Gibson, Ian W., Halloran, Philip, Hidalgo, Luis G., Horsfield, Catherine, Huang, Edmund, Kikić, Željko, Kozakowski, Nicolas, Nankivell, Brian, Rabant, Marion, Randhawa, Parmjeet, Riella, Leonardo V., Sapir-Pichhadze, Ruth, Schinstock, Carrie, Solez, Kim, Tambur, Anat R., Thaunat, Olivier, Wiebe, Chris, Zielinski, Dina, Colvin, Robert, Loupy, Alexandre, and Mengel, Michael

Published
2024
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21. Challenges in the management of the kidney allograft: from decline to failure: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Author

Ahn, Curie, Alberú, Josefina, Baliker, Mary, Bamgboye, Ebun L., Barber, Thelma, Bensouda, Melissa, Chadban, Steve J., Dadhania, Darshana M., Dębska-Ślizień, Alicja, Devresse, Arnaud, Ditzen, Beate, Fowler, Kevin, Gill, John S., Jha, Vivekanand, Khairallah, Pascale, Knoll, Greg A., Korst, Uwe, Lee, Austin, Legendre, Christophe, Lentine, Krista L., Lerma, Edgar V., Lorenz, Elizabeth C., Matas, Arthur J., Mohan, Sumit, Nazarewski, Sławomir, Noronha, Irene L., Obrador, Gregorio T., Parekh, Rulan S., Pavlakis, Martha, Pascual, Julio, Pilmore, Helen L., Rosenkranz, Alexander R., Rozen-Zvi, Benaya, Roy-Chaudhury, Prabir, Tanabe, Kazunari, Wanner, Christoph, Wasse, Haimanot, Yang, Chul-Woo, Josephson, Michelle A., Becker, Yolanda, Budde, Klemens, Kasiske, Bertram L., Kiberd, Bryce A., Loupy, Alexandre, Małyszko, Jolanta, Mannon, Roslyn B., Tönshoff, Burkhard, Cheung, Michael, Jadoul, Michel, Winkelmayer, Wolfgang C., and Zeier, Martin

Published
2023
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23. Immune response after pig-to-human kidney xenotransplantation: a multimodal phenotyping study

Author

Loupy, Alexandre, Goutaudier, Valentin, Giarraputo, Alessia, Mezine, Fariza, Morgand, Erwan, Robin, Blaise, Khalil, Karen, Mehta, Sapna, Keating, Brendan, Dandro, Amy, Certain, Anaïs, Tharaux, Pierre-Louis, Narula, Navneet, Tissier, Renaud, Giraud, Sébastien, Hauet, Thierry, Pass, Harvey I, Sannier, Aurélie, Wu, Ming, Griesemer, Adam, Ayares, David, Tatapudi, Vasishta, Stern, Jeffrey, Lefaucheur, Carmen, Bruneval, Patrick, Mangiola, Massimo, and Montgomery, Robert A

Published
2023
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24. Banff Digital Pathology Working Group: Image Bank, Artificial Intelligence Algorithm, and Challenge Trial Developments

Author

Alton B. Farris, Mariam P. Alexander, Ulysses G. J. Balis, Laura Barisoni, Peter Boor, Roman D. Bülow, Lynn D. Cornell, Anthony J. Demetris, Evan Farkash, Meyke Hermsen, Julien Hogan, Renate Kain, Jesper Kers, Jun Kong, Richard M. Levenson, Alexandre Loupy, Maarten Naesens, Pinaki Sarder, John E. Tomaszewski, Jeroen van der Laak, Dominique van Midden, Yukako Yagi, and Kim Solez

Subjects
Banff, digital pathology, artificial intelligence, machine learning, image analysis, Specialties of internal medicine, RC581-951
Abstract

The Banff Digital Pathology Working Group (DPWG) was established with the goal to establish a digital pathology repository; develop, validate, and share models for image analysis; and foster collaborations using regular videoconferencing. During the calls, a variety of artificial intelligence (AI)-based support systems for transplantation pathology were presented. Potential collaborations in a competition/trial on AI applied to kidney transplant specimens, including the DIAGGRAFT challenge (staining of biopsies at multiple institutions, pathologists’ visual assessment, and development and validation of new and pre-existing Banff scoring algorithms), were also discussed. To determine the next steps, a survey was conducted, primarily focusing on the feasibility of establishing a digital pathology repository and identifying potential hosts. Sixteen of the 35 respondents (46%) had access to a server hosting a digital pathology repository, with 2 respondents that could serve as a potential host at no cost to the DPWG. The 16 digital pathology repositories collected specimens from various organs, with the largest constituent being kidney (n = 12,870 specimens). A DPWG pilot digital pathology repository was established, and there are plans for a competition/trial with the DIAGGRAFT project. Utilizing existing resources and previously established models, the Banff DPWG is establishing new resources for the Banff community.

Published
2023
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25. Complement-activating donor-specific anti-HLA antibodies in solid organ transplantation: systematic review, meta-analysis, and critical appraisal

Author

Solaf Al-Awadhi, Marc Raynaud, Kevin Louis, Antoine Bouquegneau, Jean-Luc Taupin, Olivier Aubert, Alexandre Loupy, and Carmen Lefaucheur

Subjects
complement-activation, donor specific antibodies, anti-HLA, rejection, transplantation outcomes, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionSeveral studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking.MethodsWe conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level.ResultsIn total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p

Published
2023
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26. Qualifying a Novel Clinical Trial Endpoint (iBOX) Predictive of Long-Term Kidney Transplant Outcomes

Author

Amanda Klein, Alexandre Loupy, Mark Stegall, Ilkka Helanterä, Luke Kosinski, Eric Frey, Olivier Aubert, Gillian Divard, Kenneth Newell, Herwig-Ulf Meier-Kriesche, Roslyn Mannon, Thomas Dumortier, Varun Aggarwal, Jagdeep T. Podichetty, Inish O’Doherty, Ahmed Osama Gaber, and William E. Fitzsimmons

Subjects
kidney transplant, iBox, transplant outcomes, organ transplant, transplant clinical trial, Specialties of internal medicine, RC581-951
Abstract

New immunosuppressive therapies that improve long-term graft survival are needed in kidney transplant. Critical Path Institute’s Transplant Therapeutics Consortium received a qualification opinion for the iBOX Scoring System as a novel secondary efficacy endpoint for kidney transplant clinical trials through European Medicines Agency’s qualification of novel methodologies for drug development. This is the first qualified endpoint for any transplant indication and is now available for use in kidney transplant clinical trials. Although the current efficacy failure endpoint has typically shown the noninferiority of therapeutic regimens, the iBOX Scoring System can be used to demonstrate the superiority of a new immunosuppressive therapy compared to the standard of care from 6 months to 24 months posttransplant in pivotal or exploratory drug therapeutic studies.

Published
2023
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27. Subclinical rejection-free diagnostic after kidney transplantation using blood gene expression

Author

Badet, Lionel, Brunet, Maria, Buron, Fanny, Cahen, Rémi, Codas, Ricardo, Daoud, Sameh, Dubois, Valérie, Fournie, Coralie, Gaillard, François, Grégoire, Arnaud, Koenig, Alice, Lévi, Charlène, Morelon, Emmanuel, Pouteil-Noble, Claire, Rabeyrin, Maud, Rimmelé, Thomas, Thaunat, Olivier, Blancho, Gilles, Branchereau, Julien, Cantarovich, Diego, Chapelet, Agnès, Dantal, Jacques, Deltombe, Clément, Figueres, Lucile, Gaisne, Raphael, Garandeau, Claire, Giral, Magali, Gourraud-Vercel, Caroline, Hourmant, Maryvonne, Karam, Georges, Kerleau, Clarisse, Kervella, Delphine, Masset, Christophe, Meurette, Aurélie, Ville, Simon, Kandell, Christine, Moreau, Anne, Renaudin, Karine, Delbos, Florent, Walencik, Alexandre, Devis, Anne, Amrouche, Lucile, Anglicheau, Dany, Aubert, Olivier, Bererhi, Lynda, Legendre, Christophe, Loupy, Alexandre, Martinez, Frank, Méjean, Arnaud, Sberro-Soussan, Rébecca, Scemla, Anne, Timsit, Marc-Olivier, Zuber, Julien, Danger, Richard, Le Berre, Ludmilla, Cadoux, Marion, Papuchon, Emmanuelle, Mai, Hoa Le, Nguyen, Thi-Van-Ha, Guérif, Pierrick, Lefaucheur, Carmen, Couzi, Lionel, Del Bello, Arnaud, Kamar, Nassim, Le Quintrec, Moglie, Goutaudier, Valentin, and Brouard, Sophie

Published
2023
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28. Machine learning does not outperform traditional statistical modelling for kidney allograft failure prediction

Author

Truchot, Agathe, Raynaud, Marc, Kamar, Nassim, Naesens, Maarten, Legendre, Christophe, Delahousse, Michel, Thaunat, Olivier, Buchler, Matthias, Crespo, Marta, Linhares, Kamilla, Orandi, Babak J., Akalin, Enver, Pujol, Gervacio Soler, Silva, Helio Tedesco, Jr., Gupta, Gaurav, Segev, Dorry L., Jouven, Xavier, Bentall, Andrew J., Stegall, Mark D., Lefaucheur, Carmen, Aubert, Olivier, and Loupy, Alexandre

Published
2023
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29. Comparison of artificial intelligence and human-based prediction and stratification of the risk of long-term kidney allograft failure

Author

Gillian Divard, Marc Raynaud, Vasishta S. Tatapudi, Basmah Abdalla, Elodie Bailly, Maureen Assayag, Yannick Binois, Raphael Cohen, Huanxi Zhang, Camillo Ulloa, Kamila Linhares, Helio S. Tedesco, Christophe Legendre, Xavier Jouven, Robert A. Montgomery, Carmen Lefaucheur, Olivier Aubert, and Alexandre Loupy

Subjects
Medicine
Abstract

Divard, Raynaud et al. compare artificial intelligence (AI)-based predictions of kidney allograft failure based on electronic health records with those made by transplant physicians of varying levels of experience. The ability of physicians to predict allograft failure is limited, with superior performance seen for the AI system.

Published
2022
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32. Immunosuppressant drugs and quality-of-life outcomes in kidney transplant recipients: An international cohort study (EU-TRAIN)

Author

François R. Girardin, Anna Nicolet, Oriol Bestard, Carmen Lefaucheur, Klemens Budde, Fabian Halleck, Sophie Brouard, Magali Giral, Pierre-Antoine Gourraud, Béatrice Horcholle, Jean Villard, Joachim Marti, and Alexandre Loupy

Subjects
immunosuppressant, kidney transplant patient, quality of life, PROMS, VAS (analog visual scale), EQ5D 3L, Therapeutics. Pharmacology, RM1-950
Abstract

Introduction: Patient-Reported Outcomes (PRO) integrate a wide range of holistic dimensions that arenot captured within clinical outcomes. Particularly, from induction treatment to maintenance therapy, patient quality-of-life (QoL) of kidney transplant recipients have been sparsely investigated in international settings.Methods: In a prospective, multi-centric cohort study, including nine transplant centers in four countries, we explored the QoL during the year following transplantation using validated elicitation instruments (EQ-5D-3L index with VAS) in a population of kidney transplant patients receiving immunosuppressive therapies. Calcineurin inhibitors (tacrolimus and ciclosporin), IMPD inhibitor (mycophenolate mofetil), and mTOR inhibitors (everolimus and sirolimus) were the standard-of-care (SOC) medications, together with tapering glucocorticoid therapy. We used EQ-5D and VAS data as QoL measures alongside descriptive statistics at inclusion, per country and hospital center. We computed the proportions of patients with different immunosuppressive therapy patterns, and using bivariate and multivariate analyses, assessed the variations of EQ-5D and VAS between baseline (i.e., inclusion Month 0) and follow up visits (Month 12).Results: Among 542 kidney transplant patients included and followed from November 2018 to June 2021, 491 filled at least one QoL questionnaire at least at baseline (Month 0). The majority of patients in all countries received tacrolimus and mycophenolate mofetil, ranging from 90.0% in Switzerland and Spain to 95.8% in Germany. At M12, a significant proportion of patients switched immunosuppressive drugs, with proportion varying from 20% in Germany to 40% in Spain and Switzerland. At visit M12, patients who kept SOC therapy had higher EQ-5D (by 8 percentage points, p < 0.05) and VAS (by 4 percentage points, p < 0.1) scores than switchers. VAS scores were generally lower than EQ-5D (mean 0.68 [0.5–0.8] vs. 0.85 [0.8–1]).Discussion: Although overall a positive trend in QoL was observed, the formal analyses did not show any significant improvements in EQ-5D scores or VAS. Only when the effect of a therapy use was separated from the effect of switching, the VAS score was significantly worse for switchers during the follow up period, irrespective of the therapy type. If adjusted for patient characteristics and medical history (e.g., gender, BMI, eGRF, history of diabetes), VAS and EQ-5D delivered sound PRO measures for QoL assessments during the year following renal transplantation.

Published
2023
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33. Safety, tolerability, and efficacy of monoclonal CD38 antibody felzartamab in late antibody-mediated renal allograft rejection: study protocol for a phase 2 trial

Author

Mayer, Katharina A., Budde, Klemens, Halloran, Philip F., Doberer, Konstantin, Rostaing, Lionel, Eskandary, Farsad, Christamentl, Anna, Wahrmann, Markus, Regele, Heinz, Schranz, Sabine, Ely, Sarah, Firbas, Christa, Schörgenhofer, Christian, Kainz, Alexander, Loupy, Alexandre, Härtle, Stefan, Boxhammer, Rainer, Jilma, Bernd, and Böhmig, Georg A.

Published
2022
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34. Comparison of artificial intelligence and human-based prediction and stratification of the risk of long-term kidney allograft failure

Author

Divard, Gillian, Raynaud, Marc, Tatapudi, Vasishta S., Abdalla, Basmah, Bailly, Elodie, Assayag, Maureen, Binois, Yannick, Cohen, Raphael, Zhang, Huanxi, Ulloa, Camillo, Linhares, Kamila, Tedesco, Helio S., Legendre, Christophe, Jouven, Xavier, Montgomery, Robert A., Lefaucheur, Carmen, Aubert, Olivier, and Loupy, Alexandre

Published
2022
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35. Safety, tolerability, and efficacy of monoclonal CD38 antibody felzartamab in late antibody-mediated renal allograft rejection: study protocol for a phase 2 trial

Author

Katharina A. Mayer, Klemens Budde, Philip F. Halloran, Konstantin Doberer, Lionel Rostaing, Farsad Eskandary, Anna Christamentl, Markus Wahrmann, Heinz Regele, Sabine Schranz, Sarah Ely, Christa Firbas, Christian Schörgenhofer, Alexander Kainz, Alexandre Loupy, Stefan Härtle, Rainer Boxhammer, Bernd Jilma, and Georg A. Böhmig

Subjects
Antibody-mediated rejection, CD38, Donor-specific antibody, Felzartamab, Kidney transplantation, Monoclonal antibody, Medicine (General), R5-920
Abstract

Abstract Background Antibody-mediated rejection (ABMR) is a cardinal cause of renal allograft loss. This rejection type, which may occur at any time after transplantation, commonly presents as a continuum of microvascular inflammation (MVI) culminating in chronic tissue injury. While the clinical relevance of ABMR is well recognized, its treatment, particularly a long time after transplantation, has remained a big challenge. A promising strategy to counteract ABMR may be the use of CD38-directed treatment to deplete alloantibody-producing plasma cells (PC) and natural killer (NK) cells. Methods This investigator-initiated trial is planned as a randomized, placebo-controlled, double-blind, parallel-group, multi-center phase 2 trial designed to assess the safety and tolerability (primary endpoint), pharmacokinetics, immunogenicity, and efficacy of the fully human CD38 monoclonal antibody felzartamab (MOR202) in late ABMR. The trial will include 20 anti-HLA donor-specific antibody (DSA)-positive renal allograft recipients diagnosed with active or chronic active ABMR ≥ 180 days post-transplantation. Subjects will be randomized 1:1 to receive felzartamab (16 mg/kg per infusion) or placebo for a period of 6 months (intravenous administration on day 0, and after 1, 2, 3, 4, 8, 12, 16, and 20 weeks). Two follow-up allograft biopsies will be performed at weeks 24 and 52. Secondary endpoints (preliminary assessment) will include morphologic and molecular rejection activity in renal biopsies, immunologic biomarkers in the blood and urine, and surrogate parameters predicting the progression to allograft failure (slope of renal function; iBOX prediction score). Discussion Based on the hypothesis that felzartamab is able to halt the progression of ABMR via targeting antibody-producing PC and NK cells, we believe that our trial could potentially provide the first proof of concept of a new treatment in ABMR based on a prospective randomized clinical trial. Trial registration EU Clinical Trials Register (EudraCT) 2021-000545-40 . Registered on 23 June 2021. ClinicalTrials.gov NCT05021484 . Registered on 25 August 2021

Published
2022
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37. Dynamic prediction of renal survival among deeply phenotyped kidney transplant recipients using artificial intelligence: an observational, international, multicohort study

Author

Raynaud, Marc, Aubert, Olivier, Divard, Gillian, Reese, Peter P, Kamar, Nassim, Yoo, Daniel, Chin, Chen-Shan, Bailly, Élodie, Buchler, Matthias, Ladrière, Marc, Le Quintrec, Moglie, Delahousse, Michel, Juric, Ivana, Basic-Jukic, Nikolina, Crespo, Marta, Silva, Helio Tedesco, Jr, Linhares, Kamilla, Ribeiro de Castro, Maria Cristina, Soler Pujol, Gervasio, Empana, Jean-Philippe, Ulloa, Camilo, Akalin, Enver, Böhmig, Georg, Huang, Edmund, Stegall, Mark D, Bentall, Andrew J, Montgomery, Robert A, Jordan, Stanley C, Oberbauer, Rainer, Segev, Dorry L, Friedewald, John J, Jouven, Xavier, Legendre, Christophe, Lefaucheur, Carmen, and Loupy, Alexandre

Published
2021
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38. COVID-19 pandemic and worldwide organ transplantation: a population-based study

Author

Aubert, Olivier, Yoo, Daniel, Zielinski, Dina, Cozzi, Emanuele, Cardillo, Massimo, Dürr, Michael, Domínguez-Gil, Beatriz, Coll, Elisabeth, Da Silva, Margarida Ivo, Sallinen, Ville, Lemström, Karl, Midtvedt, Karsten, Ulloa, Camilo, Immer, Franz, Weissenbacher, Annemarie, Vallant, Natalie, Basic-Jukic, Nikolina, Tanabe, Kazunari, Papatheodoridis, Georgios, Menoudakou, Georgia, Torres, Martin, Soratti, Carlos, Hansen Krogh, Daniela, Lefaucheur, Carmen, Ferreira, Gustavo, Silva, Helio Tedesco, Jr, Hartell, David, Forsythe, John, Mumford, Lisa, Reese, Peter P, Kerbaul, François, Jacquelinet, Christian, Vogelaar, Serge, Papalois, Vassilios, and Loupy, Alexandre

Published
2021
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41. Time-dependent lymphocyte count after transplantation is associated with higher risk of graft failure and death

Author

Blancho, Gilles, Branchereau, Julien, Cantarovich, Diego, Chapelet, Agnès, Dantal, Jacques, Deltombe, Clément, Figueres, Lucile, Garandeau, Claire, Giral, Magali, Gourraud-Vercel, Caroline, Hourmant, Maryvonne, Karam, Georges, Kerleau, Clarisse, Meurette, Aurélie, Ville, Simon, Kandell, Christine, Moreau, Anne, Renaudin, Karine, Cesbron, Anne, Delbos, Florent, Walencik, Alexandre, Devis, Anne, Amrouche, Lucile, Anglicheau, Dany, Aubert, Olivier, Bererhi, Lynda, Legendre, Christophe, Loupy, Alexandre, Martinez, Frank, Sberro-Soussan, Rébecca, Scemla, Anne, Tinel, Claire, Zuber, Julien, Dujardin, Amaury, Lorent, Marine, Foucher, Yohann, and Brouard, Sophie

Published
2021
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43. Comparing the effects of two different strains of mycobacteria, Mycobacterium vaccae NCTC 11659 and M. vaccae ATCC 15483, on stress-resilient behaviors and lipid-immune signaling in rats

Author

Loupy, Kelsey M., Cler, Kristin E., Marquart, Brandon M., Yifru, Tumim W., D'Angelo, Heather M., Arnold, Mathew R., Elsayed, Ahmed I., Gebert, Matthew J., Fierer, Noah, Fonken, Laura K., Frank, Matthew G., Zambrano, Cristian A., Maier, Steven F., and Lowry, Christopher A.

Published
2021
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44. Trajectories of glomerular filtration rate and progression to end stage kidney disease after kidney transplantation

Author

Raynaud, Marc, Aubert, Olivier, Reese, Peter P., Bouatou, Yassine, Naesens, Maarten, Kamar, Nassim, Bailly, Élodie, Giral, Magali, Ladrière, Marc, Le Quintrec, Moglie, Delahousse, Michel, Juric, Ivana, Basic-Jukic, Nikolina, Gupta, Gaurav, Akalin, Enver, Yoo, Daniel, Chin, Chen-Shan, Proust-Lima, Cécile, Böhmig, Georg, Oberbauer, Rainer, Stegall, Mark D., Bentall, Andrew J., Jordan, Stanley C., Huang, Edmund, Glotz, Denis, Legendre, Christophe, Montgomery, Robert A., Segev, Dorry L., Empana, Jean-Philippe, Grams, Morgan E., Coresh, Josef, Jouven, Xavier, Lefaucheur, Carmen, and Loupy, Alexandre

Published
2021
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45. Intragraft gene expression in native kidney BK virus nephropathy versus T cell–mediated rejection: Prospects for molecular diagnosis and risk prediction

Author

Adam, Benjamin A., Kikic, Zeljko, Wagner, Siegfried, Bouatou, Yassine, Gueguen, Juliette, Drieux, Fanny, Reid, Graeme, Du, Katie, Bräsen, Jan H., D’Agati, Vivette D., Drachenberg, Cinthia B., Farkash, Evan A., Brad Farris, Alton, Geldenhuys, Laurette, Loupy, Alexandre, Nickeleit, Volker, Rabant, Marion, Randhawa, Parmjeet, Regele, Heinz, and Mengel, Michael

Published
2020
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46. The XVth Banff Conference on Allograft Pathology the Banff Workshop Heart Report: Improving the diagnostic yield from endomyocardial biopsies and Quilty effect revisited

Author

Duong Van Huyen, Jean-Paul, Fedrigo, Marny, Fishbein, Gregory A., Leone, Ornella, Neil, Desley, Marboe, Charles, Peyster, Eliot, von der Thüsen, Jan, Loupy, Alexandre, Mengel, Michael, Revelo, Monica P., Adam, Benjamin, Bruneval, Patrick, Angelini, Annalisa, Miller, Dylan V., and Berry, Gerald J.

Published
2020
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48. COVID-19-related medical research: a meta-research and critical appraisal

Author

Marc Raynaud, Huanxi Zhang, Kevin Louis, Valentin Goutaudier, Jiali Wang, Quentin Dubourg, Yongcheng Wei, Zeynep Demir, Charlotte Debiais, Olivier Aubert, Yassine Bouatou, Carmen Lefaucheur, Patricia Jabre, Longshan Liu, Changxi Wang, Xavier Jouven, Peter Reese, Jean-Philippe Empana, and Alexandre Loupy

Subjects
COVID-19, Systematic review, Critical appraisal, Quality of research, Medicine (General), R5-920
Abstract

Abstract Background Since the start of the COVID-19 outbreak, a large number of COVID-19-related papers have been published. However, concerns about the risk of expedited science have been raised. We aimed at reviewing and categorizing COVID-19-related medical research and to critically appraise peer-reviewed original articles. Methods The data sources were Pubmed, Cochrane COVID-19 register study, arXiv, medRxiv and bioRxiv, from 01/11/2019 to 01/05/2020. Peer-reviewed and preprints publications related to COVID-19 were included, written in English or Chinese. No limitations were placed on study design. Reviewers screened and categorized studies according to i) publication type, ii) country of publication, and iii) topics covered. Original articles were critically appraised using validated quality assessment tools. Results Among the 11,452 publications identified, 10,516 met the inclusion criteria, among which 7468 (71.0%) were peer-reviewed articles. Among these, 4190 publications (56.1%) did not include any data or analytics (comprising expert opinion pieces). Overall, the most represented topics were infectious disease (n = 2326, 22.1%), epidemiology (n = 1802, 17.1%), and global health (n = 1602, 15.2%). The top five publishing countries were China (25.8%), United States (22.3%), United Kingdom (8.8%), Italy (8.1%) and India (3.4%). The dynamic of publication showed that the exponential growth of COVID-19 peer-reviewed articles was mainly driven by publications without original data (mean 261.5 articles ± 51.1 per week) as compared with original articles (mean of 69.3 ± 22.3 articles per week). Original articles including patient data accounted for 713 (9.5%) of peer-reviewed studies. A total of 576 original articles (80.8%) showed intermediate to high risk of bias. Last, except for simulation studies that mainly used large-scale open data, the median number of patients enrolled was of 102 (IQR = 37–337). Conclusions Since the beginning of the COVID-19 pandemic, the majority of research is composed by publications without original data. Peer-reviewed original articles with data showed a high risk of bias and included a limited number of patients. Together, these findings underscore the urgent need to strike a balance between the velocity and quality of research, and to cautiously consider medical information and clinical applicability in a pressing, pandemic context. Systematic review registration https://osf.io/5zjyx/

Published
2021
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