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chronic allograft dysfunction

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https://www.readbyqxmd.com/read/28214296/abnormally-high-and-heterogeneous-bone-matrix-mineralization-after-childhood-solid-organ-transplantation-a-complex-pathology-of-low-bone-turnover-and-local-defects-in-mineralization
#1
Nadja Fratzl-Zelman, Helena Valta, Renata C Pereira, Barbara M Misof, Paul Roschger, Hannu Jalanko, Kathrine Wesseling-Perry, Klaus Klaushofer, Outi Mäkitie
Chronic renal, liver and heart failure in children associates with multiple skeletal complications. Increased fracture incidence often persists after transplantation and could be related to alterations in bone material properties. In the present cohort study we evaluated bone mineralization density distribution (BMDD) by quantitative backscattered electron imaging (qBEI) in 23 pediatric solid organ allograft recipients with suspected osteoporosis. We measured BMDD in the entire cross-sectional area of transiliac bone biopsies obtained from kidney (n = 9), liver (n = 9) and heart (n = 5) transplant recipients (aged 7...
February 18, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28207638/association-of-local-intrapulmonary-production-of-antibodies-specific-to-donor-major-histocompatibility-complex-class-i-with-the-progression-of-chronic-rejection-of-lung-allografts
#2
Ei Miyamoto, Hideki Motoyama, Masaaki Sato, Akihiro Aoyama, Toshi Menju, Kei Shikuma, Terumasa Sowa, Akihiko Yoshizawa, Masao Saito, Akihiro Takahagi, Satona Tanaka, Mamoru Takahashi, Keiji Ohata, Takeshi Kondo, Kyoko Hijiya, Toyofumi F Chen-Yoshikawa, Hiroshi Date
BACKGROUND: Antibody-mediated rejection may lead to chronic lung allograft dysfunction, but antibody-mediated rejection may develop in the absence of detectable donor-specific antibody (DSA) in recipient serum. This study investigated whether humoral immune responses develop not only systemically but locally within rejected lung allografts, resulting in local production of DSA. METHODS: Lewis rats received orthotopic left lung transplantation from Lewis (syngeneic control) or Brown-Norway (major histocompatibility complex-mismatched allogeneic) donor rats...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28186707/mesenchymal-stromal-cell-therapy-for-chronic-lung-allograft-dysfunction-results-of-a-first-in-man-study
#3
Daniel C Chambers, Debra Enever, Sharon Lawrence, Marian J Sturm, Richard Herrmann, Stephanie Yerkovich, Michael Musk, Peter M A Hopkins
Chronic lung transplant rejection (termed chronic lung allograft dysfunction [CLAD]) is the main impediment to long-term survival after lung transplantation. Bone marrow-derived mesenchymal stromal cells (MSCs) represent an attractive cell therapy in inflammatory diseases, including organ rejection, given their relative immune privilege and immunosuppressive and tolerogenic properties. Preclinical studies in models of obliterative bronchiolitis and human trials in graft versus host disease and renal transplantation suggest potential efficacy in CLAD...
February 1, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28185711/impact-of-gastroesophageal-reflux-and-delayed-gastric-emptying-on-pediatric-lung-transplant-outcomes
#4
Fei Jamie Dy, Dawn Freiberger, Enju Liu, Debra Boyer, Gary Visner, Rachel Rosen
BACKGROUND: Gastroesophageal reflux disease is thought to predispose to adverse lung allograft outcomes. However, little is known about the burden of gastroesophageal reflux (GER) and gastroparesis in pediatric patients. In this study we describe the burden of reflux and gastroparesis in children undergoing lung transplant, and evaluates their impact on allograft survival and rejection incidence. METHODS: This study is a retrospective analysis of pediatric lung transplant recipients who had combined pH and multichannel intraluminal impedance testing (pH-MII) and gastric-emptying scans (GES)...
January 6, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28164137/immune-responses-to-tissue-restricted-nonmajor-histocompatibility-complex-antigens-in-allograft-rejection
#5
REVIEW
Ankit Bharat, T Mohanakumar
Chronic diseases that result in end-stage organ damage cause inflammation, which can reveal sequestered self-antigens (SAgs) in that organ and trigger autoimmunity. The thymus gland deletes self-reactive T-cells against ubiquitously expressed SAgs, while regulatory mechanisms in the periphery control immune responses to tissue-restricted SAgs. It is now established that T-cells reactive to SAgs present in certain organs (e.g., lungs, pancreas, and intestine) are incompletely eliminated, and the dysregulation of peripheral immuneregulation can generate immune responses to SAgs...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28138398/comparative-analysis-of-morphological-and-molecular-motifs-in-bronchiolitis-obliterans-and-alveolar-fibroelastosis-after-lung-and-stem-cell-transplantation
#6
Danny Jonigk, Berenice Rath, Paul Borchert, Peter Braubach, Lavinia Maegel, Nicole Izykowski, Gregor Warnecke, Wiebke Sommer, Hans Kreipe, Robert Blach, Adrian Anklamm, Axel Haverich, Matthias Eder, Michael Stadler, Tobias Welte, Jens Gottlieb, Mark Kuehnel, Florian Laenger
Chronic lung allograft dysfunction (CLAD) remains the major obstacle to long-term survival following lung transplantation (LuTx). Morphologically CLAD is defined by obliterative remodelling of the small airways (bronchiolitis obliterans, BO) as well as a more recently described collagenous obliteration of alveoli with elastosis summarised as alveolar fibroelastosis (AFE). Both patterns are not restricted to pulmonary allografts, but have also been reported following haematopoietic stem cell transplantation (HSCT) and radio chemotherapy (RC)...
January 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28135784/morphologic-patterns-and-treatment-of-transplant-glomerulopathy-a-retrospective-analyse
#7
Rui Abreu, Fernanda Carvalho, Helena Viana, Isabel Mesquita, Marília Possante, Inês Aires, Fernando Caeiro, Cecília Silva, Patrícia Cotovio, Aníbal Ferreira, Francisco Remédio, Fernando Nolasco
Transplant glomerulopathy is mainly due to chronic antibody-mediated rejection and actually represents a major cause of long-term allograft failure. The lack of effective treatment remains a serious problem in transplantation. A retrospective and uni-center study was performed in 48 kidney allograft recipients with transplant glomerulopathy between January 2010 and December 2015. Median time for diagnosis was 7,1 (3,6 - 11,8) years post-transplant. Light microscopy showed severity of transplant glomerulopathy in the majority of patients (cg1=10,4%; cg2=20,8%; cg3=68,8%)...
January 30, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28124458/hepatic-ischemia-reperfusion-injury-associates-with-acute-kidney-injury-in-liver-transplantation-prospective-cohort-study
#8
Ina Jochmans, Nicolas Meurisse, Arne Neirynck, Marleen Verhaegen, Diethard Monbaliu, Jacques Pirenne
: Solid clinical prospective studies investigating the association between hepatic ischemia reperfusion injury and acute kidney injury after liver transplantation are missing. Hepatic ischemia reperfusion injury -reflected by transaminase release- induces acute kidney injury in rodents and retrospective studies suggest a similar association in man. This prospective cohort study determined risk factors for acute kidney injury in 80 adult liver-only recipients. Acute kidney injury -defined by RIFLE-criteria- developed in 21 (26%) recipients at 12 hours postreperfusion [inter quartile range: 6 hours-postoperative day 1]; 13 progressed from "Risk" to "Injury"; 5 to "Failure"...
January 25, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28120410/restrictive-allograft-syndrome-and-idiopathic-pleuroparenchymal-fibroelastosis-do-they-really-have-the-same-histology
#9
M Angeles Montero, Tina Osadolor, Reena Khiroya, M Teresa Salcedo, Jan Lukas Robertus, Alexandra Rice, Andrew G Nicholson, Antonio Roman, Victor Monforte
AIMS: Restrictive Allograft Syndrome (RAS) and idiopathic pleuroparenchymal fibroelastosis (IPPFE) are two different diseases reported to share the same histology. RAS relates to chronic allograft dysfunction in lung transplantation with IPPFE being a rare condition in native lungs. Our aim is to compare their histologies, alongside biopsies of usual interstitial pneumonia (UIP), to determine if there are differences that might help to elucidate the pathogenesis. METHODS AND RESULTS: We selected 4 post-mortem allograft lungs from patients who developed clear clinical RAS pattern, 5 biopsies diagnosed as IPPFE, 5 UIP biopsies and 5 sections of normal lung...
January 25, 2017: Histopathology
https://www.readbyqxmd.com/read/28104157/clinical-courses-of-graft-failure-caused-by-chronic-allograft-dysfunction-in-kidney-transplantation
#10
T Fujiwara, S Teruta, S Tsudaka, K Ota, H Matsuda
BACKGROUND: Chronic allograft dysfunction (CAD) is a main cause of graft failure in kidney transplantation. METHODS: We retrospectively analyzed 279 kidney transplant recipients who survived with a functioning graft for at least 2 years. CAD was defined as chronic graft deterioration, excluding other specific causes. We defined the pattern of decline in estimated glomerular filtration rate (eGFR), as follows: (1) "plateau" was defined as decline in eGFR ≤2 mL/min/1...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28103284/gene-expression-profiling-of-bronchoalveolar-lavage-cells-preceding-a-clinical-diagnosis-of-chronic-lung-allograft-dysfunction
#11
S Samuel Weigt, Xiaoyan Wang, Vyacheslav Palchevskiy, Aric L Gregson, Naman Patel, Ariss DerHovanessian, Michael Y Shino, David M Sayah, Shirin Birjandi, Joseph P Lynch, Rajan Saggar, Abbas Ardehali, David J Ross, Scott M Palmer, David Elashoff, John A Belperio
BACKGROUND: Chronic Lung Allograft Dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Although CLAD is usually not responsive to treatment, earlier identification may improve treatment prospects. METHODS: In a nested case control study, 1-year post transplant surveillance bronchoalveolar lavage (BAL) fluid samples were obtained from incipient CLAD (n = 9) and CLAD free (n = 8) lung transplant recipients. Incipient CLAD cases were diagnosed with CLAD within 2 years, while controls were free from CLAD for at least 4 years following bronchoscopy...
2017: PloS One
https://www.readbyqxmd.com/read/28101803/lung-retransplantation-in-an-adult-13%C3%A2-years-after-single-lobar-transplant-in-childhood
#12
Seiichiro Sugimoto, Shinji Otani, Takashi Ohki, Takeshi Kurosaki, Kentaroh Miyoshi, Masaomi Yamane, Shinichiro Miyoshi, Takahiro Oto
Single living-donor lobar lung transplantation provides acceptable results for critically ill children; however, an additional lung transplantation may be required in the future as the recipient grows. We describe a case of successful lung retransplantation in a grown-up patient after single lobar lung transplantation in childhood. A 23-year-old man underwent bilateral cadaveric lung retransplantation for chronic lung allograft dysfunction 13 years after right single living-donor lobar transplantation for idiopathic pulmonary arterial hypertension performed at the age of 10 years...
January 18, 2017: General Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28100545/chronic-effects-of-air-pollution-on-lung-function-after-lung-transplantation-in-the-systems-prediction-of-chronic-lung-allograft-dysfunction-sysclad-study
#13
Meriem Benmerad, Rémy Slama, Karine Botturi, Johanna Claustre, Antoine Roux, Edouard Sage, Martine Reynaud-Gaubert, Carine Gomez, Romain Kessler, Olivier Brugière, Jean-François Mornex, Sacha Mussot, Marcel Dahan, Véronique Boussaud, Isabelle Danner-Boucher, Claire Dromer, Christiane Knoop, Annick Auffray, Johanna Lepeule, Laure Malherbe, Frederik Meleux, Laurent Nicod, Antoine Magnan, Christophe Pison, Valérie Siroux
An irreversible loss in lung function limits the long-term success in lung transplantation. We evaluated the role of chronic exposure to ambient air pollution on lung function levels in lung transplant recipients (LTRs).The lung function of 520 LTRs from the Cohort in Lung Transplantation (COLT) study was measured every 6 months. The levels of air pollutants (nitrogen dioxide (NO2), particulate matter with an aerodynamic cut-off diameter of x µm (PMx) and ozone (O3)) at the patients' home address were averaged in the 12 months before each spirometry test...
January 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28100499/gremlin1-plays-a-key-role-in-kidney-development-and-renal-fibrosis
#14
Rachel H Church, Imran Ali, Mitchel Tate, Deborah Lavin, Arjun Krishnakumar, Helena M Kok, Roel Goldschmeding, Finian Martin, Derek Brazil
Grem1, an antagonist of bone morphogenetic proteins, plays a key role in embryogenesis. A highly specific temporospatial gradient of Grem1 and BMP signalling is critical to normal lung, kidney and limb development. Grem1 levels are increased in renal fibrotic conditions including acute kidney injury, diabetic nephropathy, chronic allograft nephropathy and immune glomerulonephritis. A small number of grem1-/- whole body knockout mice on a mixed genetic background (8 %) are viable, with a single, enlarged left kidney and grossly normal histology...
January 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28090432/update-on-chronic-lung-allograft-dysfunction
#15
Jason M Gauthier, Ramsey R Hachem, Daniel Kreisel
Chronic lung allograft dysfunction (CLAD) encompasses a range of pathologies that cause a transplanted lung to not achieve or maintain normal function. CLAD manifests as airflow restriction and/or obstruction and is predominantly a result of chronic rejection. Three distinct phenotypes of chronic rejection are now recognized: bronchiolitis obliterans, neutrophilic reversible allograft dysfunction, and restrictive allograft syndrome. Recent investigations have revealed that each phenotype has a unique pathology and histopathological findings, suggesting that treatment regimens should be tailored to the underlying etiology...
September 2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/28078769/interleukin-1%C3%AE-induced-release-of-interleukin-8-by-human-bronchial-epithelial-cells-in-vitro-assessing-mechanisms-and-possible-treatment-options
#16
REVIEW
Hannelore Bellon, Elly Vandermeulen, Carolien Mathyssen, Annelore Sacreas, Stijn E Verleden, Tobias Heigl, Hanne Vriens, Elise Lammertyn, Charles Pilette, Peter Hoet, Robin Vos, Bart M Vanaudenaerde, Geert M Verleden
BACKGROUND: Survival after lung transplantation is hampered by chronic lung allograft dysfunction (CLAD). Persistently elevated BAL-neutrophilia is observed in some patients despite treatment with azithromycin, which may be induced by IL-1α. Our aim is to establish an in vitro model, assess mechanistic pathways and test different therapeutic strategies of IL-1α induced release of IL-8 by human bronchial epithelial cells. METHODS: Bronchial epithelial cells (16HBE) were stimulated with IL-1α with or without azithromycin or dexamethasone...
January 12, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28062570/moving-biomarkers-toward-clinical-implementation-in-kidney-transplantation
#17
Madhav C Menon, Barbara Murphy, Peter S Heeger
Long-term kidney transplant outcomes remain suboptimal, delineating an unmet medical need. Although current immunosuppressive therapy in kidney transplant recipients is effective, dosing is conventionally adjusted empirically on the basis of time after transplant or altered in response to detection of kidney dysfunction, histologic evidence of allograft damage, or infection. Such strategies tend to detect allograft rejection after significant injury has already occurred, fail to detect chronic subclinical inflammation that can negatively affect graft survival, and ignore specific risks and immune mechanisms that differentially contribute to allograft damage among transplant recipients...
January 6, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28058223/acute-antibody-mediated-rejection-after-intestinal-transplantation
#18
Guo-Sheng Wu, Ruy J Cruz, Jun-Chao Cai
AIM: To investigate the incidence, risk factors and clinical outcomes of acute antibody-mediated rejection (ABMR) after intestinal transplantation (ITx). METHODS: A retrospective single-center analysis was performed to identify cases of acute ABMR after ITx, based on the presence of donor-specific antibody (DSA), acute tissue damage, C4d deposition, and allograft dysfunction. RESULTS: Acute ABMR was identified in 18 (10.3%) out of 175 intestinal allografts with an average occurrence of 10 d (range, 4-162) after ITx...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28052095/metabolomic-profiling-in-individuals-with-a-failing-kidney-allograft
#19
Roberto Bassi, Monika A Niewczas, Luigi Biancone, Stefania Bussolino, Sai Merugumala, Sara Tezza, Francesca D'Addio, Moufida Ben Nasr, Alessandro Valderrama-Vasquez, Vera Usuelli, Valentina De Zan, Basset El Essawy, Massimo Venturini, Antonio Secchi, Francesco De Cobelli, Alexander Lin, Anil Chandraker, Paolo Fiorina
BACKGROUND: Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease. METHODS: To explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine) and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft) 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3)...
2017: PloS One
https://www.readbyqxmd.com/read/28039098/efficacy-and-tolerability-of-interferon-free-antiviral-therapy-in-kidney-transplant-recipients-with-chronic-hepatitis-c
#20
Inmaculada Fernández, Raquel Muñoz-Gómez, Juan M Pascasio, Carme Baliellas, Natalia Polanco, Nuria Esforzado, Ana Arias, Martín Prieto, Lluis Castells, Valentín Cuervas-Mons, Olga Hernández, Javier Crespo, José L Calleja, Xavier Forns, María-Carlota Londoño
BACKGROUND & AIMS: The development of direct-acting antiviral agents (DAAs) is a major step forward in the treatment of hepatitis C (HCV). The aims of the study were to evaluate the efficacy and tolerability of DAAs in kidney transplant (KT) recipients. METHODS: Hepa-C is a Spanish registry of patients treated with DAAs in which clinical, virological and analytical data were prospectively included. We report on the data from 103 KT recipients who received DAAs. RESULTS: The most commonly used DAAs combinations were sofosbuvir/ledipasvir (n=59, 57%) and sofosbuvir+daclatasvir (n=18, 17%)...
December 28, 2016: Journal of Hepatology
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