Chronic Allograft Failure:
Natural History, Pathogenesis,
Diagnosis and Management
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Edited By:Nasimul AhsanMayo Clinic Transplant Center Jacksonville, Florida, USA ISBN: 978-1-58706-153-0 Published: 2008-07-14 This book may be purchased as an eBook (pdf) for $99, or individual chapters (pdf) may be purchased from the list below for $19. |
This book addresses one of the largest unmet needs in transplantation, the need to reduce late allograft loss. In the current era, it is reasonable to expect that most allografts will serve their recipients through their life span and death with preserved graft function the ultimate goal for all transplant recipients. However, long term allograft survival has not paralleled improvements made in short term survival. Each year a percentage of the existing organ transplant patients will lose their grafts. The problem of late allograft failure is due in part to pathogenic processes, to drug management, and to transplant patient care delivery.
This book pulls together the science in this area and serves as a resource and as a catalyst for further research. The book has been divided into sections covering the entirety of chronic allograft loss from basic science consideration to clinical implications. The goal of this book is to provide the reader with an overview of long term problems in solid organ transplantation. This overview not only includes the diagnosis of immunologic and non-immunologic causes of chronic graft loss but current management as well as novel therapies for future application. This book will make a useful contribution to the literature.
Chapters available from this book
Pancreas and Islet Allograft Failure
Patrick G. Dean, Yogish Kudva and Mark D. Stegall
The treatment of diabetes mellitus is aimed at improving glycemic control. Establishing relatively tight control using exogenous insulin has been shown to reduce the ophthal‑mologic, neurologic and renal complications of diabetes mellitus. However, achieving a glycosylated hemoglobin (Hgb A1C)...
Cytomegalovirus and Allograft Failure after Solid Organ Transplantation
Hugo Bonatti, Walter C. Hellinger and Raymund R. Razonable
Allograft rejection and infections are the two major complications of solid organ transplantation. These clinical entities are intimately interrelated, with one predisposing to the other, in a bidirectional relationship. Allograft rejection and its treatment predisposes to various infections, most c...
Polyomavirus Type BK‑Associated Nephropathy and Renal Allograft Graft Loss: Natural History, Patho‑Physiology, Diagnosis and Management
Nasimul Ahsan
In recent years, polyomavirus type BK‑associated nephropathy (PVAN) has emerged as an important cause of renal allograft dysfunction and graft loss. It is estimated to affect up to 10% of renal transplant recipients, with allograft failure rate as high as 80%. After primary infection in immuno...
Experimental Gene Therapy of Heart Transplantation
Giuseppe Vassalli, Charles Seydoux, Pierre Vogt, Manuel Pascual and Ludwig K. von Segesser
Maintenance of a functional graft requires life‑long immuno-suppression to prevent rejection by the immune system. Unfortunately, current immunosuppressive agents do not effectively prevent chronic rejection and are associated with significant comorbidity. Therefore, improved strategies that t...
Renal Allograft Survival: Epidemiologic Considerations
Titte R. Srinivas and Herwig-Ulf Meier-Kriesche
Kidney transplantation is the treatment of choice for patients with end‑stage renal disease. From initial pioneering experiences 50 years ago, kidney transplantation has become a clinical reality with over a 100,000 patients living with a functioning kidney transplant at the end of 2004 in the...
Islet of Langerhans: Cellular Structure and Physiology
Amanda Jabin Gustafsson and Md. Shahidul Islam
Islets of Langerhans, named after their discoverer Paul Langerhans, constitute a unique endocrine organ of critical importance in the metabolism of nutrients and energy homeostasis. Individual islets consist of three major types of electrically excitable cells, namely b‑cells that secrete insu...
The Immunology of Chronic Allograft Injury
Raphael Thuillier and Roslyn B. Mannon
The causes of chronic graft injury are diverse and are dependant on the recipient, donor organ and immunosuppressive strategy. In this chapter, we explore the contribution of the immune system to this problem, recognizing that nonimmune factors have been shown to contribute to chronic injury as well...
Diagnosis of Chronic Graft Failure after Lung Transplantation
David B. Erasmus, Andras Khoor and Cesar A. Keller
Since 1984, when bronchiolitis obliterans (BO) was recognized as the main factor influencing long‑term survival after lung and heart‑lung transplantation, this condition has remained the main cause of morbidity and mortality one year after transplant. It is characterized by submucosal ly...
The Role for Cytokine Responses in the Pathogenesis of Lung Allograft Dysfunction
John A. Belperio, Brigette Gomperts, Samuel Weigt and Michael P. Keane
Lung transplantation is now considered to be a therapeutic option for patients with end‑stage pulmonary disorders. However, due to problems of allograft dysfunction, 5 year survival rates are only 42%, as compared to greater than 70% for other solid organ transplantations. There are three dist...
Dendritic Cell‑Based Approaches to Organ Transplantation
Andrea Meinhardt and Giuseppe Vassalli
Dendritic cells (DCs) take up antigens at peripheral sites and migrate to T‑cell areas of lymph nodes and spleen, where they present antigenic peptides to T‑cells. As such, DCs initiate innate and adaptive immune responses to microorganisms and other antigens, including alloantigens in o...
Late Allograft Failure: Liver
Jeffrey S. Crippin
Dysfunction and subsequent loss of a liver allograft can have dire consequences for the recipient. Acute and chronic rejection, an ongoing risk for the lifetime of the allograft in the vast majority of liver transplant recipients, is a minor problem, except when levels of immunosuppression fall. The...
Predictive Parameters of Graft Failure
Paola Romagnani
The incidence of end stage renal disease (ESRD) is increasing at a faster rate than the availability of kidney donors, but unfortunately the improvement in short‑term graft survival rates has not been followed by substantial amelioration in long‑term outcome. Almost half of cadaveric all...
Analyzing Graft Failure in the Scientific Registry of Transplant Recipients: The Sources and Nature of the Data Available
David M. Dickinson, Gregory N. Levine, Douglas E. Schaubel and Robert A. Wolfe
This chapter uses information from a series of articles published in previous editions of the SRTR Report on the State of Transplantation and the OPTN/SRTR Annual Report to assemble a practical background useful for a researcher becoming familiar with data available for analysis of transplant outcom...
Pathology of Kidney Allograft Dysfunction
Bela Ivanyi
The pathologic features, clinical correlations and differential diagnoses of the major causes of kidney allograft dysfunction are reviewed. Rejection is an inflammatory process of the recipient during which donor cells bearing alloantigens are destroyed; the rejection process is classified tradition...
Liver Allograft Failure Due to Recurrent Disease: Pathology
Urmila Khettry and Atoussa Goldar-Najafi
Liver transplantation (LT) is an acceptable mode of therapy for end‑stage liver diseases of varying etiology. With the exception of certain disorders of genetic and toxic etiology, most other diseases can recur in the liver allograft. The recurrent diseases can share clinicopathological featur...
The Basic Science of Lung Allograft Failure
Trudie Goers, Ryan Fields and Thalachallour Mohanakumar
Although great strides have been made in the field of lung transplantation with respect to surgical technique, treatment of acute rejection and post‑operative management, the long term success of lung transplantation is limited by the development of chronic rejection as manifest by the bronchi...
Treatment of Chronic Graft Failure after Lung Transplantation
Francisco G. Alvarez and Cesar A. Keller
Since lung transplantation became a reality 25 years ago, improvements in lung preservation, surgical techniques and post‑operative management have improved the 1‑year patient survival to almost 80%. Beyond the first year, though, bronchiolitis obliterans (BO), considered a form of chron...
Ischemia‑Reperfusion Injury: Pathophysiology and Clinical Approach
Maria Teresa Gandolfo and Hamid Rabb
Significant ischemia‑reperfusion injury (IRI) occurs in every deceased donor organ transplant and in some live donor ones. In renal transplants, it remains the leading contributor to delayed graft function (DGF), which in turn predisposes to increased acute rejection and worse long‑term ...
Chronic Allograft Dysfunction—Liver
Susan Lerner, Pauline Chen and Paul Martin
In the United States, more than six thousand patients undergo liver transplantation (LT) annually with generally excellent outcomes reflected in patient survival of 88% at one year and 80% at three years and graft survival of 83% and 74%. Advances in immunosuppression have made acute cellular reject...
Graft Loss due to Vascular Complications
Barbara Stange, Matthias Glanemann and Natascha C. Nüssler
Vascular complications occur in about 10% of patients undergoing orthotopic liver transplantation. Depending on the involved vessels and the time point after liver transplantation, the clinical course of these patients may vary considerably, ranging from complete absence of symptoms to acute or chro...
Pharmacotherapeutic Options in Solid Organ Transplantation
Jennifer Trofe, Anikphe Imoagene-Oyedeji and Roy D. Bloom
Over the past decade, advances in immunosuppressive therapies have resulted in lower rates of acute rejection and consequently, significant improvements in patient and graft survival after solid organ transplantation. Increasingly successful outcomes have focused attention on the complications of lo...
Heat Shock Protein 47 in Chronic Allograft Nephropathy
Takashi Taguchi and Mohammed Shawkat Razzaque
Chronic allograft nephropathy (CAN), associated with late allograft dysfunction is caused by alloantigen‑dependent and ‑independent mechanisms that eventually progresses to irreversible interstitial fibrosis. Heat shock protein 47 (HSP47) is a collagen‑specific molecular chaperone ...
Cardiac Allograft Vasculopathy
Jignesh K. Patel and Jon A. Kobashigawa
Over the last four decades, cardiac transplantation has been the preferred therapy for select patients with end‑stage heart disease. Improvements in immunosuppression, donor procurement, surgical techniques and posttransplant care over this period have resulted in a substantial decrease in acu...
Pathological Aspects of Pancreas Allograft Failure
Cinthia B. Drachenberg and John C. Papadimitriou
Pancreas allograft failure results from a variety of causes, highly dependent on the time posttransplantation. In the early posttransplantation period pancreas allograft failure is usually related to “technical failures”, including thrombosis, infection, pancreatitis, anastomotic leak and bleedi...
Metabolic Indicators of Islet Graft Dysfunction
Raquel N. Faradji, Kathy Monroy, Misha Denham, Camillo Ricordi and Rodolfo Alejandro
Assessing b‑cell mass and function is of great importance in the islet transplant setting but it has been challenging. Although achieving insulin independence has been one of the most important end points of islet transplantation (IT), it is critical that it is associated with good glycemic co...
The Graft: Emerging Viruses in Transplantation
Deepali Kumar and Atul Humar
Emerging infections have become increasingly recognized as causes of morbidity, mortality, graft dysfunction, graft failure and donor‑transmitted infections. Specifically, a number of emerging viral pathogens have had significant adverse effects in transplant patients. These viruses may occur ...
Hepatitis C Virus Infection as a Risk Factor for Graft Loss after Renal Transplantation
José M. Morales and B. Dominguez-Gil
Liver disease is an important complication after renal transplantation and Hepatitis C virus (HCV) infection is the most frequent cause of liver disease. Clinical course is irrelevant in the short‑term, excepting rare cases of fibrosing cholestatic hepatitis. However, in the long run, HCV infe...
Hepatic Allograft Loss: Pathogenesis, Diagnosis and Management
Mohammad Ali
Liver transplantation is the established therapeutic modality for the treatment of both acute and chronic end stage liver disease. After successful transplantation 85% recipients usually survive one year, 69% for five years and 61% for ten years. Well functioning liver allograft is the prime issue o...
Solid Organ Transplantation—An Overview
Roy D. Bloom, Lee R. Goldberg, Andrew Y. Wang, Thomas W. Faust and Robert M. Kotloff
Human solid organ transplantation became a reality in 1954 with the performance of the first successful kidney transplant by Dr. Joseph Murray and colleagues. The ensuing 15‑20 years witnessed an expansion of the clinical science to encompass transplantation of heart, liver, pancreas and lung ...
Recurrent Glomerular Disease in the Allograft: Risk Factors and Management
Hani M. Wadei, Xochiquetzal J. Geiger and Martin L. Mai
In contrast to the major improvement in immunologically mediated allograft loss, little advances have been made in the area of recurrent glomerular disease which currently stands as the third leading cause of renal allograft loss. This chapter will focus on the current status of recurrent glomerular...
Chronic Allograft Failure: Past, Present and Future
Basit Javaid and John D. Scandling
Transplantation is the treatment of choice for irreversible organ damage. According to United Network for Organ Sharing (UNOS) data, by the end of June 2007, 400,291 solid organ transplants had been performed in the United States since 1988.1 In 2006, a total of 28,933 solid organ transplants includ...
Chronic Allograft Enteropathy
Gonzalo P. Rodriguez-Laiz and Kishore R. Iyer
Current immunosuppression has made small bowel transplantation the standard of care for patients with short bowel syndrome who face complications of total parenteral nutrition (TPN). With standardization and refinement of operative techniques and improvements in rates and outcomes of acute cellular ...
The Pathology of Heart Allograft Rejection
Jon Carthy, Heather Heine, Alice Mui and Bruce McManus
In 1905, the innovative French surgeon Alexis Carrel performed the first heterotopic canine heart transplant with Charles Guthrie. Twenty years later, the concept of cardiac allograft rejection was proposed by Frank Mann at the Mayo Clinic to explain the eventual failure of heterotopic canine allogr...
Liver Transplantation—An Overview
Tiffany E. Kaiser, E. Steve Woodle and Guy W. Neff
Liver transplantation has offered thousands of patients a new lease on life. The improvements in survivals are attributed to the various treatment modalities before and after liver transplantation. Certain diseases such as chronic Hepatitis C virus (HCV) infection is an epidemic that is currently th...
Polyomavirus Allograft Nephropathy: Clinico‑Pathological Correlations
Volker Nickeleit and Harsharan K. Singh
Polyomavirus nephropathy (PVN) is primarily caused by a productive intra‑renal BK virus infection. It is often an iatrogenic complication due to long term over immunosuppression and frequently leads to chronic kidney dysfunction and failure. Post renal transplantation, PVN has emerged as a maj...
Islet Transplantation
Breay W. Paty and A.M. James Shapiro
Islet transplantation restores endogenous insulin secretion in individuals with type 1 diabetes by infusing insulin‑secreting islet cells, isolated from cadaveric pancreata, into the liver. The immune mediated destruction of insulin‑secreting beta cells within pancreatic islets that occu...
Clinico-Pathological Correlations of Chronic Allograft Nephropathy
Jeremy R. Chapman
Despite, or perhaps because of, common usage “CAN” is a poorly defined term. At Westmead we combine both pathology and physiology to arrive at the following definition: “Progressive graft dysfunction accompanied by chronic interstitial fibrosis, tubular atrophy, vascular occlusive changes and ...
Chronic Pancreas Allograft Failure
Elizabeth K. Gross and Rainer W.G. Gruessner
Apancreas transplant is the only treatment of diabetes mellitus that establishes long‑term insulin independence. As of December 31, 2006, about 20,000 pancreas transplants had been performed in the United States, with 1‑year graft survival rates of >80% and patient survival rates of >95%...
Introducing Chronic Graft Failure
Harold C. Yang
Over the past 50 years the short‑term improvement in one year graft survival in solid organ transplantation has improved dramatically. The latest statistics from the Scientific Registry of Transplant Recipients (SRTR) for 2006 demonstrate graft survivals in kidney, liver, lung and heart transp...


