Genetic determinants of delayed graft function after kidney transplantation

BACKGROUND: Intracellular concentration of reactive oxygen species is held within tight physiological limits by enzymes with scavenging and repair functions. Under extreme conditions such as prolonged cold ischemia, these enzymes may be unable to adequately protect the organ, resulting in reperfusion injury that renders the graft dysfunctional after transplantation. In this study, we investigated normal human variation of some of these inducible enzymes to determine if certain phenotypes could be identified that are associated with a reduced risk of delayed graft function (DGF). METHODS: Polymerase chain reaction was performed to differentiate polymorphisms for manganese superoxide dismutase and three classes of glutathione-S-transferase in donors and recipients of transplants with over 24 hr of cold ischemia. The data attained was analyzed compared with the presence or absence of DGF, defined as the requirement of hemodialysis in the first week after transplantation. RESULTS: Enzyme polymorphisms were defined for 229 recipients and 104 of their respective donors. Patients receiving a kidney from a donor who expressed GSTM1*B either alone or in combination with GSTM1*A experienced significantly lower rates of DGF (P <0.05). No association was found between any enzyme polymorphism in the recipients and the development of DGF. CONCLUSIONS: The identification of a genetic allele, which is protective against reperfusion injury, generates the possibility for defining polymorphisms at the time of tissue typing to give insight to the inherent biological risk of DGF that an organ possesses

The Brain-Dead Organ Donor

Addressing all aspects of brain death and thoroughly detailing how a potential organ donor should be maintained to ensure maximum use of the organs and cells, The Brain-Dead Organ Donor: Pathophysiology and Management is a landmark addition to the literature. This first-of-its-kind, multidisciplinary volume will be of interest to a large section of the medical community. The first section of the book reviews the historical, medical, legal, and ethical aspects of brain death. That is followed by two chapters on the pathophysiology of brain death as investigated in small and large animal models. This includes a review of the many hormonal changes, including the neuroendocrine- adrenergic ‘storm’, that takes place during and following the induction of brain death, and how they impact metabolism. The next section of the book reviews various effects of brain death, namely its impact on thyroid function, the inflammatory response that develops, and those relating to innate immunity. The chapters relating to assessment and management of potential organ donors will be of interest to a very large group of transplant surgeons and physicians as well as critical care and neurocritical care physicians and nurses. Neurologists, endocrinologists, neurosurgeons, and pathologists will also be interested, especially in the more basic science sections on various aspects of brain-death and hormonal therapy. Organ procurement organizations and transplant coordinators worldwide will also be interested in this title. Other chapters will be of interest to medical historians, medico-legal experts, and ethicists.CONTENIDO: Introduction, Dimitri Novitzky, David K. C. Cooper, Pages 1-6 -- Historical Aspects of the Diagnosis of Death, Félix Bacigalupo, Daniela A. Huerta Fernández, Pages 7-11 -- The Determination of Brain Death, Curtis M. Keller, Boris Chulpayev, Michael Hoffmann, Pages 13-19 -- Legal Aspects of Brain Death and Organ Donorship, Ricky T. Munoz, Mark D. Fox, Pages 21-35 -- Ethical Issues in Organ Donation from Brain-Dead Donors, Mark D. Fox, Ricky T. Munoz, Pages 37-53 -- Pathophysiology of Brain Death in Small Animal Models, Bernhard Floerchinger, Nicholas L. Tilney, Stefan G. Tullius, Pages 55-64 -- Pathophysiology of Brain Death and Effects of Hormonal Therapy in Large Animal Models, Dimitri Novitzky, Winston N. Wicomb, David K. C. Cooper, Pages 65-90 -- The Efficacy of Thyroid Hormone Therapy in Brain-Dead Heart Donors: A Review of Thyroid Function in Health and Disease, Lawrence E. Shapiro, Tatiana Baron, Pages 91-105 -- The Inflammatory Response to Brain Death, Anne Barklin, Christine Lodberg Hvas, Else Toennesen, Pages 107-119 -- The Influence of Brain Death and Intensive Care Management on Donor Organs: Assessment of Inflammatory Markers, Wayel Jassem, Susan V. Fuggle, Pages 121-129 -- Brain Death-Induced Inflammation: Possible Role of the Cholinergic Anti-inflammatory Pathway, Simone Hoeger, Benito A. Yard, Pages 131-138 -- Innate Immunity and Injury During Brain Death: Opportunities for Intervention, Marc A. Seelen, Henri G. D. Leuvenink, Rutger J. Ploeg, Pages 139-145 -- Selection of the Brain-Dead Potential Organ Donor, Kadiyala V. Ravindra, Keri E. Lunsford, Paul C. Kuo, Pages 147-154 -- Infectious Disease Aspects of the Brain-Dead Potential Organ Donor, Nicole M. Theodoropoulos, Michael G. Ison, Pages 155-176 -- Malignancy in the Brain-Dead Organ Donor, Michael A. Nalesnik, Ron Shapiro, Michael G. Ison, Pages 177-189 -- Early Clinical Experience of Hormonal Therapy in the Brain-Dead Potential Organ Donor, Dimitri Novitzky, Burcin Ekser, David K. C. Cooper, Pages 191-207 -- Assessment, Monitoring, and Management of Brain-Dead Potential Organ Donors in the USA, Demetrios Demetriades, Lydia Lam, Pages 209-216 -- Assessment, Monitoring, and Management of Brain-Dead Potential Organ Donors in Europe, Gabriel J. Echeverri, Bruno G. Gridelli, Pages 217-235 -- Assessment, Monitoring, and Management of Brain-Dead Potential Organ Donors in Australia, Peter S. Macdonald, Anders E. M. Aneman, Deepak Bhonagiri, Daryl A. Jones, Gerry O’Callaghan, Helen I. Opdam et al., Pages 237-249 -- Management of the Brain-Dead Organ Donor: Perspectives of the Transplant Coordinator, Nicole T. Farina, David K. C. Cooper, Pages 251-261 -- Surgical Aspects of Thoracic and Abdominal Organ Procurement from Brain-Dead Donors, Michael J. Anstadt, Paul C. Kuo, Kadiyala V. Ravindra, Pages 263-281 -- Impact of Brain Death on Storage of the Heart, Winston N. Wicomb, David K. C. Cooper, Pages 283-288 -- Impact of Brain Death on Abdominal Organs and Allograft Preservation Strategies, Coney Bae, Anthony Watkins, Scot D. Henry, James V. Guarrera, Pages 289-298 -- Functional Repair of Brain Death-Induced Injury, Henri G. D. Leuvenink, Marc A. Seelen, Rutger J. Ploeg, Pages 299-310 -- Functional Repair of Brain Death-Injured Donor Lungs, Jonathan C. Yeung, Marcelo Cypel, Shaf Keshavjee, Pages 311-320 -- Thyroid Hormone Therapy to the Recipient of a Heart from a Brain-Dead Donor, Dimitri Novitzky, David K. C. Cooper, Pages 321-331 -- Current and Potential Future Trends in the Management of the Brain-Dead Organ Donor, Octavio E. Pajaro, James K. Kirklin, Pages 333-341 -- Maximizing Utilization of the Potential Deceased Donor: The Challenge Continues,Eliezer Katz,Pages 343-35