KIDNEY TRANSPLANTATION – NEW PERSPECTIVES Edited by Magdalena Trzcińska Kidney Transplantation – New Perspectives Edited by Magdalena Trzcińska Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access articles distributed under the Creative Commons Non Commercial Share Alike Attribution 3.0 license, which permits to copy, distribute, transmit, and adapt the work in any medium, so long as the original work is properly cited. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published articles. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Davor Vidic Technical Editor Teodora Smiljanic Cover Designer Jan Hyrat Image Copyright Sebastian Kaulitzki, 2010. Used under license from Shutterstock.com First published August, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Kidney Transplantation – New Perspectives, Edited by Magdalena Trzcińska p. cm. ISBN 978-953-307-684-3 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Chapter 1 Mechanisms of T Lymphocytes in the Damage and Repair Long Term after Renal Ischemia Reperfusion Injury 3 Dolores Ascon and Miguel Ascon Chapter 2 Characteristics, Detection, and Clinical Relevance of Alloantibodies in Kidney Transplantation 15 Andrew Lobashevsky Chapter 3 Urothelial Carcinoma in Renal Transplant Recipients 55 Ming-Kuen Lai, Shuo-Meng Wang and Huai-Ching Tai Chapter 4 Immune Monitoring of Kidney Recipients: Biomarkers to Appreciate Immunosuppression -Associated Complications 65 Philippe Saas, Jamal Bamoulid, Béatrice Gaugler and Didier Ducloux Chapter 5 Urinary Fructose-1,6-Bisphosphatase (FBP-1,6) and N-Acetyl-β-Hexosaminidase (HEX) in Monitoring Kidney Transplantation - Literature Review 89 Alina Kępka, Sławomir Dariusz Szajda, Napoleon Waszkiewicz, Sylwia Chojnowska, Paweł Pludowski, Jerzy Robert Ładny and Krzysztof Zwierz Chapter 6 Evaluation of CTLA-4, CD28 and CD86 Genes Polymorphisms in Acute Renal Allograft Rejection among Tunisian Patients 111 Henda Krichen, Imen Sfar, Taieb Ben Abdallah, Rafika Bardi, Ezzeddine Abderrahim, Saloua Jendoubi-Ayed, Mouna Makhlouf, Houda Aouadi, Hammadi Ayadi, Khaled Ayed and Yousr Gorgi Chapter 7 Urinary Proteomics and Renal Transplantation 127 Elisenda Banon-Maneus, Luis F Quintana and Josep M Campistol Chapter 8 Pharmacogenetics and Renal Transplantation 147 Chi Yuen Cheung VI Contents Chapter 9 Tolerance in Kidney Transplantation 163 Faouzi Braza, Maud Racape, Jean-Paul Soulillou and Sophie Brouard Chapter 10 Mechanisms of Tolerance: Role of the Thymus and Persistence of Antigen in Calcineurin-Induced Tolerance of Renal Allografts in MGH Miniature Swine 179 Joseph R. Scalea, Isabel Hanekamp and Kazuhiko Yamada Chapter 11 Operational Tolerance after Renal Transplantation in the Regenerative Medicine Era 193 Giuseppe Orlando, Pierpaolo Di Cocco, Lauren Corona, Tommaso Maria Manzia, Katia Clemente, Antonio Famulari and Francesco Pisani Chapter 12 Ischemia Reperfusion Injury in Kidney Transplantation 213 Bulent Gulec Chapter 13 Transforming Growth Factor-Beta in Kidney Transplantation: A Double-Edged Sword 223 Caigan Du Chapter 14 The Impact of Ischemia and Reperfusion Injury in Kidney Allograft Outcome 235 Valquiria Bueno Chapter 15 ROCK Inhibition – A New Therapeutic Avenue in Kidney Protection 249 Stefan Reuter, Dominik Kentrup and Eckhart Büssemaker Chapter 16 Post-Tx Renal Monitoring with B-Flow Ultrasonography 275 Paride De Rosa, Enrico Russo andVincenzo Cerbone Chapter 17 Immune Gene Polymorphisms Associate with Outcome in Kidney Transplantation 291 Katri Haimila, Noora Alakulppi and Jukka Partanen Chapter 18 Sleep Disturbances Among Dialysis Patients 317 Gianluigi Gigli, Simone Lorenzut, Anna Serafini and Mariarosaria Valente Chapter 19 Bridging the ‘Gap’ in Developing Countries: At what Expense? 329 Chulananda DA Goonasekera Preface To our Patients without whose effort, goodwill and trust no progress in medicine would be possible The emergence of transplantology has definitely launched a new era in the history of medicine. And although the first attempts at transplanting organs would frequently end up with a failure, it is thanks to the determination and courage of pioneer doctors and sacrificial attitude of the patients that we can enjoy today’s state of knowledge and potential in the field of organ transplantation. It should also not be forgotten that clinical transplantology owes its development and getting well-grounded to the development of such fields of medicine as nephrology or clinical immunology. A clear dynamic development has been observed over the last decades also in the field of immunosuppressant treatment. At present immunosuppressant drugs are more effective and safer, posing a lower risk for side-effects to the patients. Many years have passed since the first successful kidney transplantation and the method, although no longer considered a medical experiment, is still perceived as controversial and, as such, it triggers many emotions. And even though family transplants attract more social understanding, unfortunately the same is still not true for recovering and transplanting organs from a dead donor. Much confusion concerns mostly the concept of brain death and its diagnostic procedures. Doubt is found even among medical doctors or heath-care related communities, most frequently due to a lack of knowledge or wrong understanding of the concept of brain death. Many years and conscious educational efforts are still needed to make kidney transplantation, for many people the only chance for an active lifestyle and improved quality of life, win common social acceptance and stop triggering negative connotations. The need of mass transplantology education has been already effectively implemented in many EU countries, the United States and in Canada; it is spread not only by the medical community but also by the emerging and already active associations of organ transplant patients. The statistics gathered by the World Health Organization (WHO) show that in 2009 in 27 EU countries 17886 thousand kidney transplants were performed, namely 668 (0.6%) transplantation cases more than in 2008. The statistics demonstrate that the X Preface number of transplantations performed has been regularly increasing for more than twenty years. Apart from the transplantation controversies piling up over the years and transplantation not always winning social acceptance, transplantologists also face many other medical difficulties. Much research covers the phenomenon of graft rejection and algorithms of post-kidney-transplant procedure, and the effectiveness of new drugs is being tested. A growing potential of transplantology is also due to the advancement of research into the significance of gene polymorphism, the potential of the application of the achievements of proteomics in diagnostics (e.g. allowing for identifying urine proteins differentiating between active inflammatory changes in kidneys) or numerous research on various aspects of the immune system functioning. The authors of chapters published herein are experts in their respective fields. The chapters selected are of high level of content, and the fact that their authors come from many different countries, and sometimes even cultures, has facilitated a comprehensive and interesting approach to the problem of kidney transplantation. The authors cover a wide spectrum of transplant-related topics: significance of research into gene polymorphism, possibilities of applying techniques offered by proteomics, the effect of ischemia or flow disturbances on the kidney graft, monitoring its function after transplantation as well as multi-aspect research and analyses of immunologic mechanisms. The book does not disregard the problem of mental aspects, essential especially from the patient’s perspective. As the editor, I wish to thank all the authors for their cooperation, research efforts, literature reviews and their precious clinical observations as well as for their desire to share with the medical community their precious experience without which this book would not be possible. Finally, on behalf of all the authors I wish to express hope that our publication will not only facilitate access to the latest scientific achievements in the field but also enhance a further progress in transplantology and propagating the idea all across the world. Magdalena Trzcińska, MD. University Hospital of Collegium Medicum in Bydgoszcz, Psychiatry Department, Nicolaus Copernicus University in Torun, Poland [...]... IRI A, Normal mouse kidney (no IRI) B and C, Sham-operated mice kidneys showing normal histology 3 and 24 h after surgery, respectively D, IRI mouse kidney showing same proteinaceous casts in tubules 3 h after renal IRI E, IRI kidney showing severe damage 24 h after renal IRI (Pictures used with permission and courtesy of the original authors [18]) 4 Kidney Transplantation – New Perspectives Lymphocyte... expressed after IRI in kidney 8 Kidney Transplantation – New Perspectives 5 Upregulation of cytokines and chemokines long term after IRI Expression of cytokines Cytokine and chemokines are known to modulate lymphocyte and kidney cell interactions to mediate kidney injury and fibrosis We found (19) an increased intracellular cytokine production of TNF-α and IFN-γ by CD3T+ cells infiltrating kidneys after 24... kidney from one of the recipients was removed 23 days after transplantation despite therapeutic intervention (Sturgill et al., 1984) Thus, CAs can cause irreversible changes after renal transplantation that may lead to graft loss High concentrations of CAs in the serum may represent a potential explanation for hyperacute graft injury in non-HLA sensitized patients 24 Kidney Transplantation – New Perspectives. .. Grigoryev DN, Liu M, Tuder RM, Rabb H Kidney ischemia– reperfusion injury induces caspase-dependent pulmonary apoptosis Am J Physiol Renal Physiol 2009;297:F12 5–3 7 [62] Feltes C, Rabb H: Acute kidney injury leads to pulmonary endothelial cell transcriptional, cytoskeletal and apoptotic changes ASN renal week 2009, San Diego; 2009 14 Kidney Transplantation – New Perspectives [63] Hoke TS, Douglas IS, Klein... the transplanted kidney Transplantation 1997; 64: 94 5–9 47 [2] Bonventre JV, Zuk A: Ischemic acute renal failure: An inflammatory disease? Kidney Int 66: 48 0–4 85, 2004 [3] Terasaki PI, Cecka JM, Gjertson DW et al survival rates of kidney transplants from spousal and living unrelated donors N Engl J Med 1995; 333: 33 3–3 36 [4] Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW Acute kidney injury,... arthritis: a three-colour cytometric analysis Int J Exp Pathol 1997; 78: 33 1–3 36 [29] Santamaria M, Marubayashi M, Arizon JM et al The activation antigen CD69 is selectively expressed on CD8+ endomyocardium infiltrating T lymphocytes in human rejecting heart allografts Hum Immunol 1992; 33: 1–4 12 Kidney Transplantation – New Perspectives [30] Crispin JC, Martinez A, de Pablo P et al Participation of... responsible to produce inflammatory mediators not only causing local kidney structure damage, but also the severe effects 2 Kidney Transplantation – New Perspectives on the other long distance organs, including lung, hearth, intestine, brain, liver, bone medulla Here we describe the trafficking of T lymphocytes into the mice (male C57BL/6J) kidneys both, in normal mice, earlier (3 to 24 h), and long term... weeks after renal IRI In kidneys, the CD4+CD69+, CD8+CD69+, CD4+CD44hiCD62L-, and CD4+NK1.1+ cells were also depleted by approximately 98%, in relationship with the cell profiles of nondepleted control mice (data are not showed) 6 Kidney Transplantation – New Perspectives Histology of structural damage after long term ischemia To observe the degree of structural damage of ischemic kidneys after 6 weeks... therapy J Clin Invest 2004;114: 5–1 4 [21] Bonventre JV, Weinberg JM Recent advances in the pathophysiology of ischemic acute renal failure J Am Soc Nephrol 2003;14:219 9–2 10 [22] Rabb H The T cell as a bridge between innate and adaptive immune systems: implications for the kidney Kidney Int 2002;61:193 5–4 6 [23] Li L, Okusa MD Blocking the Immune respone in ischemic acute kidney injury: the role of adenosine... al., 2004; Yung et al., 2007); however, data analysis of kidney transplants that has been performed across ABO barriers has not revealed statistically significant differences between the A (donor) →B (recipient) or B (donor) →A (recipient) groups (Squifflet et al., 2004; Sugiyama et al., 2005; Valli et al., 2009) 22 Kidney Transplantation – New Perspectives Anti-A/B blood group antibodies belong to . KIDNEY TRANSPLANTATION – NEW PERSPECTIVES Edited by Magdalena Trzcińska Kidney Transplantation – New Perspectives Edited by Magdalena. produce inflammatory mediators not only causing local kidney structure damage, but also the severe effects Kidney Transplantation – New Perspectives 2 on the other long distance organs,. not showed). Kidney Transplantation – New Perspectives 6 Histology of structural damage after long term ischemia To observe the degree of structural damage of ischemic kidneys after 6