Article
Surgery
Daniel S. Ramon, Danielle M. Troop, Theresa N. Kinard, Caroline C. Jadlowiec, Margaret S. Ryan, Winston R. Hewitt, Linda G. Olsen, Andres Jaramillo, Timucin Taner, Raymond L. Heilman
Summary: Simultaneous liver-kidney transplant (SLKT) with donor-specific antibodies (DSA) is common, but after a second liver transplant, an abrupt increase in DSA levels against the kidney led to antibody-mediated rejection (AMR). The clearance of antibodies depended on the HLA antigens expressed by the transplanted liver cells.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Surgery
Vincent Pernin, Nicole Bec, Anais Beyze, Alexis Bourgeois, Ilan Szwarc, Coralie Champion, Anthony Chauvin, Celine Rene, Georges Mourad, Pierre Merville, Jonathan Visentin, Helene Perrochia, Lionel Couzi, Christian Larroque, Moglie Le Quintrec
Summary: The glycosylation profile of IgG3 dnDSA is associated with the risk of ABMR occurrence, with low sialylation and high GlcNAc bisection being potentially predictive factors. Further studies are needed to confirm the clinical significance of DSA glycosylation in predicting ABMR and graft survival.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Surgery
Anat R. Tambur, Carrie Schinstock, Chelsea Maguire, David Lowe, Byron Smith, Mark Stegall
Summary: Reductions in cPRA calculated per antibody titer provide a more accurate assessment of the effectiveness of desensitization treatment for transplant candidates. The study indicates that changes greater than 2 titers are clinically meaningful. Therefore, calculating cPRA per titer is a reliable and simplified approach for risk stratification in desensitization trials.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Immunology
Felix Poppelaars, Mariana Gaya da Costa, Bernardo Faria, Siawosh K. Eskandari, Marc A. Seelen, Jeffrey Damman
Summary: This study investigated the impact of TNF-alpha gene polymorphisms on kidney graft survival after transplantation, revealing that the G-allele of the TNF rs3093662 polymorphism in donor kidneys is associated with a higher risk of immediate graft loss and worse long-term kidney graft survival.
JOURNAL OF INFLAMMATION RESEARCH
(2022)
Review
Surgery
Edmund Huang, Angela Q. Maldonado, Christian Kjellman, Stanley C. Jordan
Summary: Imlifidase, derived from Streptococcus pyogenes, is a novel agent with potential for HLA desensitization and antibody-mediated rejection in kidney transplantation. Clinical trials have shown rapid degradation of anti-HLA donor-specific antibodies, facilitating HLA-incompatible transplantation. Early experiences with imilfidase highlight considerations regarding kinetics of antibodies, timing of complementary therapies, and interference with cross match assays.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Surgery
Nattawat Klomjit, Mireille El Ters, Benjamin A. Adam, Priya Sampathkumar, Raymund R. Razonable, Sandra J. Taler, Timucin Taner, Mariam Priya Alexander
Summary: Neutralizing monoclonal antibodies like bamlanivimab show promise in treating COVID-19 in kidney transplant recipients, but their impact on kidney allograft histology is unclear. A case study reported diffuse peritubular capillary C4d staining following bamlanivimab treatment in a kidney transplant recipient with stable kidney function at 6 months post-biopsy.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Surgery
Jason M. Zimmerer, Jing L. Han, Chelsea M. Peterson, Qiang Zeng, Bryce A. Ringwald, Clarissa Cassol, Sachi Chaudhari, Madison Hart, Jessica Hemminger, Anjali Satoskar, Mahmoud Abdel-Rasoul, Jiao-Jing Wang, Robert T. Warren, Zheng J. Zhang, Christopher K. Breuer, Ginny L. Bumgardner
Summary: CCR5 KO kidney transplant recipients have high levels of alloantibodies and develop pathology similar to human antibody-mediated rejection. The deficiency in quantity and function of alloprimed CXCR5(+)CD8(+) T cells contributes to high alloantibody and AMR in CCR5 KO recipient mice, which can be rescued with adoptive cell therapy using alloprimed CXCR5(+)CD8(+) T cells.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Surgery
Qingyong Xu, Puneet Sood, Dennis Helmick, Jon S. Lomago, Amit D. Tevar, Adriana Zeevi
Summary: This case study reports a patient awaiting a second kidney transplantation who tested positive for B cell flow cytometry crossmatch 37 days after receiving the COVID-19 vaccine. The emergence of antibodies to HLA-DR7 following vaccination highlights the potential impact of COVID-19 immunization on alloimmunity among transplant candidates. Utilizing multiple assays and history of allo-sensitization is crucial in assessing immunological risks associated with organ transplantation.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Surgery
Scott Davis, Christopher Wiebe, Kristen Campbell, Cheri Anobile, Michael Aubrey, Erik Stites, Monica Grafals, Elizabeth Pomfret, Peter Nickerson, James E. Cooper
Summary: This study evaluated HLA-DR and -DQ molecular mismatch to predict the risk of DSAs in renal transplant patients, and found that different levels of tacrolimus exposure may modulate this risk. The results showed that HLA molecular mismatch can serve as a reproducible and clinically relevant tool to stratify patients by alloimmune risk and help guide personalized immunosuppression management.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Surgery
Jasper Callemeyn, Heleen Ameye, Evelyne Lerut, Aleksandar Senev, Maarten Coemans, Elisabet Van Loon, Ben Sprangers, Vicky Van Sandt, Maud Rabeyrin, Valerie Dubois, Olivier Thaunat, Dirk Kuypers, Marie-Paule Emonds, Maarten Naesens
Summary: The study evaluated the changes in the Banff classification for antibody-mediated rejection (ABMR) and their impact on transplant outcomes and case numbers, finding an increase in cases from Banff'01 to Banff'13 and variable outcomes for reclassified sABMR in Banff'17. The clinical and histological heterogeneity of ABMR is inadequately represented in a binary classification system.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Surgery
Rachel M. Engen, Aneta M. Jedraszko, Michael A. Conciatori, Anat R. Tambur
Summary: High-resolution HLA typing is essential for histocompatibility assessment in transplantation, but imputation tools like HaploStats and HLA Matchmaker show varying levels of accuracy, with significant errors especially for non-Caucasian individuals. Eplet analysis reveals additional inaccuracies, cautioning against widespread clinical or research use of imputation tools.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Surgery
Madhuri Ramakrishnan, Timothy Fields, Da Zhang, Itunu O. Owoyemi, Aditi Gupta, Jeffrey A. Klein, Nicholas S. Herrera, Mallika Gupta, Diane M. Cibrik
Summary: This case report describes a rare occurrence of lipoprotein deposition-related kidney disease in a transplant recipient, associated with Apolipoprotein E2 homozygosity. Treatment with fenofibrate, angiotensin enzyme inhibition, and angiotensin receptor blockade resulted in a reduction in proteinuria and maintained stable kidney function.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Surgery
Yohei Doi, Makoto Tsujita, Takayuki Hamano, Yoshitsugu Obi, Tomoko Namba-Hamano, Toshihide Tomosugi, Kenta Futamura, Manabu Okada, Takahisa Hiramitsu, Norihiko Goto, Akira Nishiyama, Asami Takeda, Shunji Narumi, Yoshihiko Watarai, Yoshitaka Isaka
Summary: Cholecalciferol supplementation did not significantly improve allograft outcomes in kidney transplant recipients, with no significant impact on eGFR change compared to placebo. However, it showed detrimental effects in patients with eGFR <45 mL/min/1.73 m(2).
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Immunology
Nicholas G. Larkins, Lloyd D'Orsogna, Anne Taverniti, Ankit Sharma, Aron Chakera, Doris Chan, Anoushka Krishnan, Germaine Wong, Wai H. Lim
Summary: High resolution HLA typing is crucial for eplet compatibility and specificity of DSA. NGS and LD typing show high concordance but significant differences. Inaccurate DSA assignment from LD typing may inappropriately exclude candidates.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Surgery
Christian Kjellman, Angela Q. Maldonado, Kristoffer Sjoholm, Bonnie E. Lonze, Robert A. Montgomery, Anna Runstrom, Tomas Lorant, Niraj M. Desai, Christophe Legendre, Torbjorn Lundgren, Bengt von Zur Muhlen, Ashley A. Vo, Hakan Olsson, Stanley C. Jordan
Summary: Imlifidase is a cysteine proteinase that can cleave IgG and convert a positive crossmatch to negative, enabling kidney transplantation between previously HLA incompatible pairs. Studies have shown that recipients of imlifidase-enabled allografts have comparable outcomes to other highly sensitized patients undergoing HLA-incompatible transplantation.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Review
Urology & Nephrology
Jasper Callemeyn, Baptiste Lamarthee, Alice Koenig, Priyanka Koshy, Olivier Thaunat, Maarten Naesens
Summary: The detection of mismatched human leukocyte antigens by adaptive immune cells is the main cause of transplant rejection. However, recent observations have questioned the traditional dichotomy between T-cell mediated rejection and antibody-mediated rejection, leading to a need for a more integrated view of kidney transplant rejection. This review highlights the gaps in the current classification of rejection, provides an overview of the expanding insights into the mechanisms of allorecognition, and discusses how these insights could improve our understanding and clinical approach to kidney transplant rejection.
KIDNEY INTERNATIONAL
(2022)
Article
Statistics & Probability
Maarten Coemans, Geert Verbeke, Maarten Naesens
Summary: This study examines the diagnostic value of estimated glomerular filtration rate (eGFR) in kidney graft rejection by building a joint model that combines characteristics of transition models and shared parameter models. Applying the model to data from University Hospitals Leuven, the study concludes that a negative deviation from the mean eGFR slope increases the probability of rejection in indication biopsies, but using the eGFR profile alone has limited benefit for diagnosing rejection when considering biopsy history. Methodologically, the study fills a gap in the biomarker literature by relating a frequently measured continuous outcome with a less frequently measured binary indicator, and the developed joint transition model is versatile and applicable to other research settings.
STATISTICAL MODELLING
(2023)
Article
Immunology
Aleksandar Senev, Bryan Ray, Evelyne Lerut, Jayasree Hariharan, Christine Heylen, Dirk Kuypers, Ben Sprangers, Marie-Paule Emonds, Maarten Naesens
Summary: This study found that patients highly and broadly sensitized to non-HLA targets are at increased risk of ABMR histology after kidney transplantations in the absence of HLA-DSA. Additionally, some pretransplant non-HLA autoantibodies are individually associated with increased rates of ABMR histology. However, further studies are needed to determine whether these associations are clinically relevant and represent causality.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Sukhdeep S. Jatana, Hedi Zhao, Laurine M. Bow, Emanuele Cozzi, Ibrahim Batal, Tillie Horak, Alexandre Amar-Zifkin, Carrie Schinstock, Medhat Askar, Darshana M. Dadhania, Matthew Cooper, Maarten Naesens, Edward S. Kraus, Ruth Sapir-Pichhadze
Summary: This study systematically assessed the definition and prognostic implications of HLA incompatibility in transplant outcomes, finding heterogeneity in the definition and incomplete reporting of variables. The risk of bias in studies examining the association between death-censored graft failure and HLA incompatibility was high. Therefore, optimizing HLA compatibility assessment and standardizing the reporting of variables are necessary for improving transplant outcomes and promoting international collaboration.
Article
Surgery
Anna Buxeda, Laura Llinas-Mallol, Javier Gimeno, Dolores Redondo-Pachon, Carlos Arias-Cabrales, Carla Burballa, Adrian Puche, Miguel Lopez-Botet, Jose Yelamos, Carlos Vilches, Maarten Naesens, Maria Jose Perez-Saez, Julio Pascual, Marta Crespo
Summary: Isolated microvascular inflammation (iMVI) is a rare phenotype that cannot be classified as antibody-mediated rejection (ABMR) in recent Banff classifications because it lacks HLA donor-specific antibodies or C4d deposition. In this study, we compared peripheral blood leukocyte distribution and inflammatory infiltrates in kidney transplant biopsies among ABMR, iMVI, and normal cases. We found that iMVI had fewer lymphocytes and peripheral T cells compared to ABMR and normal cases, but more NKG2A+ NK cells. iMVI also showed decreased plasma cell infiltration and increased cytotoxic T cell infiltration compared to ABMR.
AMERICAN JOURNAL OF TRANSPLANTATION
(2023)
Article
Urology & Nephrology
Agathe Truchot, Marc Raynaud, Nassim Kamar, Maarten Naesens, Christophe Legendre, Michel Delahousse, Olivier Thaunat, Matthias Buchler, Marta Crespo, Kamilla Linhares, Babak J. Orandi, Enver Akalin, Gervacio Soler Pujol, Helio Tedesco Silva, Gaurav Gupta, Dorry L. Segev, Xavier Jouven, Andrew J. Bentall, Mark D. Stegall, Carmen Lefaucheur, Olivier Aubert, Alexandre Loupy
Summary: In this study, machine learning models were developed and compared to traditional approaches for predicting kidney allograft outcomes. Despite good overall performances, the machine learning models did not outperform the traditional Cox-Based Prognostication System in predicting kidney allograft failure. Therefore, the study supports the continued use of traditional statistical approaches for kidney graft prognostication.
KIDNEY INTERNATIONAL
(2022)
Article
Immunology
Claire Tinel, Baptiste Lamarthee, Stephane Gazut, Elisabet Van Loon, Florent Von Tokarski, Aurelien Benon, Virginia Sauvaget, Victor Garcia-Paredes, Mickael Menager, Lise Morin, Laila Aouni, Nicolas Cagnard, Marion Rabant, Christophe Legendre, Fabiola Terzi, Marie Essig, Wilfried Gwinner, Maarten Naesens, Pierre Marquet, Dany Anglicheau
Summary: Increasing evidence suggests that microRNAs are involved in the pathophysiology of renal diseases, including kidney transplantation. In this study, the researchers investigated the changes in circulating microRNA expression and their involvement in antibody-mediated rejection. They found that certain microRNAs were significantly decreased in samples with rejection, and these microRNAs were associated with myeloid-related pathways and CD14+ monocytes.
Letter
Urology & Nephrology
Angelica Pagliazzi, Elisabet Van Loon, Maarten Naesens
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Meeting Abstract
Immunology
Ewout Muylle, Nele Van de Winkel, Antoine Dubois, Gert De Hertogh, Arne Maes, Greet Kerckhofs, Steven Pans, Vincent Vandecaveye, Marie-Paule Emonds, Diethard Monbaliu, Emilio Canovai, Tim Vanuytsel, Jacques Pirenne, Laurens Ceulemans
Article
Infectious Diseases
S. Jahanbakhsh, J. Howland, M. O. Ndayishimiye Uwineza, M. T. Thwaites, C. M. Pillar, A. W. Serio, D. M. Anastasiou, D. A. Hufnagel
Summary: Omadacycline demonstrated intracellular activity against M. abscessus, similar to tigecycline, but not against clarithromycin and amikacin.
JAC-ANTIMICROBIAL RESISTANCE
(2023)
Article
Surgery
Dennis A. J. van den Broek, Soufian Meziyerh, Klemens Budde, Carmen Lefaucheur, Emanuele Cozzi, Dominique Bertrand, Covadonga Lopez del Moral, Anthony Dorling, Marie-Paule Emonds, Maarten Naesens, Aiko P. J. de Vries
Summary: Solid phase immunoassays have improved the detection of donor-specific antibodies (DSA) to human leukocyte antigens (HLA) in kidney transplantation, but the monitoring of DSA in recipients with stable graft function is not universally accepted as standard care. This consensus report aims to assess the clinical utility of DSA monitoring in recipients without signs of graft dysfunction using the Wilson & Junger criteria and presents the findings and recommendations of a dedicated workgroup on subclinical DSA monitoring.
TRANSPLANT INTERNATIONAL
(2023)
Article
Surgery
Oriol Bestard, Olivier Thaunat, Maria Irene Bellini, Georg A. Boehmig, Klemens Budde, Frans Claas, Lionel Couzi, Lucrezia Furian, Uwe Heemann, Nizam Mamode, Rainer Oberbauer, Liset Pengel, Stefan Schneeberger, Maarten Naesens
Summary: Different types of kidney transplantations have different patient/graft outcomes. Immunological and non-immunological risk stratification is important for patients in clinical trials. A working group from the European Society for Organ Transplantation submitted a request to the European Medicines Agency for advice on clinical trial endpoints. The EMA's final response highlighted several key points regarding immunological risk and testing methods in kidney transplantation.
TRANSPLANT INTERNATIONAL
(2022)
Article
Surgery
Luuk Hilbrands, Klemens Budde, Maria Irene Bellini, Fritz Diekmann, Lucrezia Furian, Josep Grinyo, Uwe Heemann, Dennis A. Hesselink, Alexandre Loupy, Rainer Oberbauer, Liset Pengel, Marlies Reinders, Stefan Schneeberger, Maarten Naesens
Summary: Clinical study endpoints that assess efficacy of interventions in patients with chronic renal insufficiency can be applied to kidney transplantation trials due to pathophysiological similarities. Glomerular filtration rate (GFR) and estimated (e)GFR trajectories have been used as primary endpoints in clinical trials for chronic kidney disease (CKD), and similar approaches can be considered for kidney transplantation trials.
TRANSPLANT INTERNATIONAL
(2022)
Article
Surgery
Maarten Naesens, Stefan Schneeberger
Summary: This special issue of Transplant International explores the interaction between the European Society for Organ Transplantation (ESOT) and the European Medicines Agency (EMA) regarding kidney transplantation research. The articles discuss current issues and propose improvements in assessing the outcomes of kidney transplantation. The hope is that through discussions and recommendations, a consensus can be reached on clinical trial endpoints and risk stratification, leading to better quality research and improved long-term outcomes for kidney transplant recipients.
TRANSPLANT INTERNATIONAL
(2022)
