Cardiac disease is the major cause of death in dialysis patients, accounting for over one third of deaths. This book focuses on myocardial function and dysfunction in chronic uremia. It is aimed at practicing and training nephrologists, cardiologists, and internists, and at research workers in the field. We have tried to produce an up-to-date, in-depth review of the subject by inviting experts in clinical epidemiology, pathophysiology, and thera peutics to write the 18 chapters. The book is divided into three sections. The first section comprises five chapters that provide an overview of the burden of illness associated with cardiac disease in end-stage renal disease and a review of clinical epidemi ological aspects of various cardiac diseases that occur in renal patients. The second section discusses abnormalities of left ventricular contractility and mass, and the factors that predispose to both systolic and diastolic disorders. The importance of hypertension, anemia, hyperparathyroidism, hyper lipidemia, and diabetes mellitus in predisposing to these abnormalities is reviewed splendidly by researchers active in these areas. The final section concentrates on therapeutics. Data and opinion on management of congestive heart failure, cardiomyopathy, coronary artery disease, hypertension, and arrhythmias are provided. In editing this book, we have reviewed an extensive literature, but un fortunately we have become more aware that substantial gaps in our knowl edge exist. Insufficient high-quality clinical research has been undertaken xiii xiv Preface regarding the various cardiac diseases that occur in end-stage renal disease."

Drug dosage in renal insufficiency has become an toxication. In 1975, his Poison Index was pub important facet of nephrology, a subspeciality of lished, first in German, and two years later in internal medicine which is only 30 years young but English, with supplements in 1979 and 1983. This constantly growing in scope and importance. Two volume has become an obligatory reference in more thirds of all drugs are partially, mainly, or exclu than 2500 dialysis units. sively excreted by the kidneys. In the presence of Based on GOnter Seyffart's experience and renal insufficiency, dose adjustments are therefore knowledge in this field, the plans for this book obligatory. In patients on dialysis, drug elimination matured in 1984, a logical step in view of his by this route must also be considered. untiring effort and diligence. In order to deal with As the reader of this book will discover, 20 more than 1200 different drugs and almost 4000 percent of currently used drugs are contraindicated references, 21 contributors were sollicited, while it where there is any degree of renal insufficiency, took six years to complete the work. The major and for at least another 60 percent a dose reduc share of the effort was thus left to the main author tion is required. It is obvious, therefore, that the and editor and he has produced a concise work of detailed knowledge required can never be com impressive clarity.

Therapeutic immunosuppression has very broad applications in clinical medicine, ranging from prevention and treatment of organ and bone marrow transplant rejection, management of various autoimmune disorders (e.g., rheumatoid arthritis), skin disease, and asthma. Whereas traditionally only a small repertoire of immunosuppressive agents was available for clinical use, recent discoveries have significantly increased the number of approved agents, resulting in numerous trials to further evaluate their potential. In addition, products of the biotechnology industry - monoclonal antibodies, cytokines, cytokine antagonists, and other products of genetic engineering that target key molecular pathways in disease pathogenesis - have either already made, or are on the verge of making an important impact on treatment. There is also considerable interest in the potential of cell-based therapies (particularly hematopoietic stem and dendritic cell therapy) of allo- and autoimmunity. Important recent advances in the immunotherapy of allergic diseases are also covered in this book. Gene therapy offers considerable promise for suppressing pathogenic processes in either transplantation or autoimmune disorders. The possibility of combining these important new advances to maximize benefit to the patient, and to minimize possible untoward effects (which are also given extensive coverage in this book), is one of the most exciting challenges of contemporary medicine. This volume is intended both for practising physicians and surgeons and for biomedical scientists at the graduate/postdoctoral levels, and is designed to provide the theory behind these various approaches to immunosuppression, and to provide state-of-the-art reviews of current developments in each area. Each chapter is contributed by one or more experts in the field. There was a need to bring this information together in a single volume, as much of the key recent developments have been dispersed throughout the biomedical literature, largely in specialized journals. Since, as in the past, important developments in immunosuppressive therapy in one branch of medicine (i.e. transplantation) are likely to benefit another (e.g., dermatology, rheumatology, gastroenterology), cross-disciplinary coverage of the mechanistic basis of the various therapeutic strategies in a single volume is likely to convey the potential of advances in therapy in the most coherent manner possible.

Immunosuppression in solid organ transplantation is currently experiencing a worldwide revival since new drugs are now available and others are under development. In order to contribute to the design of future strategies, a critical approach of surrogate endpoints is given and long-term side effects are analysed, together with the impact of non-compliance, quality-of-life and economical parameters. In this book, international specialists have set up the scientific rationale and provided new bases for further immunosuppressive strategies.

This book, the proceedings of the 32nd International Conference on Transplantation and Clinical Immunology, held in Lyon, France, on May 25-26, 2000, addresses novel issues in terms of changing indications for transplantation in the management of organ failure, whether humans will remain the only source for organ procurement, prospects for engineering in organ replacement, and whether transplantation will remain the most appropriate approach to organ failure. Some promising treatments are approached, such as enzymic and biochemical replacement, gene therapy, tolerance induction, stem cell transplantation, and xenotransplantation. In addition to the constant improvement in conservative management of organ failure in general, ongoing research in selected fields is reported in the proceedings, such as liver transplantation vs artificial liver, novel dialysis strategies vs evolving immunosuppression in kidney transplantation, islets transplantation and external implantable insulin pumps vs pancreas transplantation in diabetic patients, circulatory assistance and intramyocardial myoblast injection vs heart transplantation. Pivotal experience in selected emerging transplantations is included, that is, small bowel, limb, skin and neuronal transplantation. Such fascinating perspectives raise medical, economical, and ethical problems which are discussed in this book.

Volume 2 of Contnnporary Xephrology updates the major developments which ha\'e occurred during the past 2 years in 15 major areas of both basic and clinical nephrology. In addition, this volume has a section, Chapter 8, \uitten by Drs. Pederson, Llach, and Papper, from the Med- ical School at the Universitv of Oklahoma, which reviews the recent developments on nonilwasive diagnostic techniques in nephrology. The other chapters are presented in such a way as to emphasize the major advances that have occurred in the different areas in the last 2 years. In Chapter 1, Dr. Schafer analyzes in detail the new information available regarding the action of aldosterone both in anuran membranes and in the mammalian kidney. Drs. Knox and Romero, in Chapter 2, update the information accrued du ring the last 2 years in the area of renal hemodynamics and sodium chloride excretion. In the area of renal me- tabolism (Chapter 3), Schoolwerth, Little, and Idell-Wenger review in detail the metabolism of lipids in the kidney and its potential relation to renal function. This is, to the best of our knowledge, the first compre- hensive review of this subject in any textbook of nephrology. Dr. Dunn provides an authoritative review of the major advances in the rapidly expanding field of prostaglandins with particular emphasis on renal prostaglandins (Chapter 4). Drs. Batlle and Kurtzman update new con- cepts of acid-base phvsiology and pathophysiology, and Dr.

After a decade or longer, approximately one-third of individuals with either type 1 or type 2 diabetes commence a downhill course in which decreasing renal function and failing vision define a Renal-Retinal Syndrome, dominating all aspects of life and presaging early death. Only a generation ago, survival after onset of end-stage renal disease (ESRD) in diabetes was limited because rehabilitation was preempted by blindness, limb amputation, stroke, and heart disease. By 1998, however, team management has improved the outlook, with preserved sight and return to work and home responsibilities, usually for a decade or longer, following kidney transplantation and laser photocoagulation. Recognition of the critical requirement for blood pressure regulation and metabolic control are central themes in management. In this unique book, the accomplishments of ophthalmologists, nephrologists, diabetologists, transplant surgeons, and basic scientists are blended into a strategic approach that may be readily applied by all those caring for diabetic patients. Each of twenty-one presentations suitable for primary care physicians, as well as for subspecialists concerned with macrovascular and microvascular complications of diabetes, is placed in perspective by an introductory editorial analysis. Promising near-term innovative therapies, including insertion of genetically engineered beta cells or polymer-coated islets of Langerhans, interdiction of kinins that promote retinal angiogenesis, and prevention of synthesis of advanced glycosylated endproducts (AGEs), are presented in detail. While comprehensive care of diabetic patients reflects multiple incremental advances that in sum afford major benefit, this text envisions further remarkable changes likely to suppress and possibly entirely prevent the Diabetic Renal-Retinal Syndrome.

Although it has been appreciated for many years that immune processes underlie most types of glomerulonephritis, it is the recent explosion in knowl edge of cellular and molecular immunology that has prompted another book on the subject. The understanding of the mechanisms involved in renal injury requires the integration of information from in vitro cell-culture systems, experimental models of disease, and clinical studies. This volume draws on all of these sources in an attempt to explain current concepts of nephritis. Increased emphasis is placed on autoimmune processes, as opposed to the deposition of circulating immune complexes, although it will be apparent that these may overlap in the area of "in situ" immune complex formation. Of central importance in autoimmunity is the relationship between antigen pre senting cells (including B cells) expressing MHC class II molecules, autoan tigenic peptides, T helper lymphocytes, and various effector cells. The mechanisms by which the immune system may lead to tissue injury are also becoming better understood, and consideration is given to the role of inflam matory cells, the complement proteins, and soluble factors such as cytokines and eicosanoids."

Nocturia: Causes, Consequences and Clinical Approaches is the first volume exclusively on the topic of nocturia and is designed to be a comprehensive treatise on the subject. The volume is organized into 11 chapters first introducing and defining nocturia and its impact to patients and society, followed by chapters dealing with predictors and risk factors; relationship to sleep disorders; overactive bladder; and water homeostasis. Therapeutic areas addressing nocturia are covered in specific chapters and include pharmacotherapy affecting the bladder, prostate and kidneys as well as behavioral therapy and surgical intervention. Separate chapters are devoted to alternative therapies as well as the impact of nocturia in the elderly. The volume closes with a chapter presenting avenues for future investigation into the etiology and management of nocturia. Clinical case scenarios inclusive of figures and tables illuminate the evaluation and management of patients with nocturia. Nocturia: Causes, Consequences and Clinical Approaches will give physicians and related healthcare providers the background to understand the conditions causing nocturia, how nocturia affects society and the basis for its rational treatment. It will be used as a state of the art reference by urologists, urogynecologists, internists, nephrologists, pulmonologists, endocrinologists and sleep medicine specialists.

Currently, individuals interested in seeking an in-depth discussion of transplantation immunology must seek individual articles published in several journals, or extrapolate information from various non-transplant immunology textbooks. The purpose of this text is to provide the reader with a single source of information for the basic science of immunobiology of organ transplantation. It is unique that it focuses on immunobiology from the basic research side, with an emphasis on the cellular and molecular levels. The readers will be physicians, scientists, and graduate students interested and engaged in the study of immunology as it relates to allo- and xenotransplantation. This book is designed to be the reference standard for the immunobiology of transplantation.

This conference and monograph were the result of many collective efforts. The whole concept was formulated one early Wednesday morning at our weekly research meeting at Children's Hospital in our division of urology. We have been most fortunate to have a close collaboration with Bob Levin, Ed Macarak, and Pam Howard who have helped steer the course of our division's growing interest in basic science. At our weekly meetings our laboratory fellow will summarize their current work. Other ongoing areas of investigation in our labs and elsewhere are discussed. We have always made an effort to try and understand what other groups are doing who are working in the area of bladder smooth muscle research. It occurred to us that the best way to really know what everyone working in this field was doing would be to sponsor a 2-day meeting where we could all gather to discuss our ongoing work. A major limitation of the annual meeting of the American Urologic Association or the urology section of the American Academy of Pediatrics is that the scientfic sessions are limited as these are meant to be primarily clinical meetings (as they should be). For this reason the idea of a meeting devoted solely to research about the urinary bladder had great appeal. In addition to allowing for longer presentations than the standard 5 to 7 minutes, every effort would be made to encourage a dialogue amongst the presenters and the audience.

Death on Hemodialysis: Preventable or Inevitable? presents the transactions of the Brooklyn meeting, held in April 1993, including an analysis by Scribner and Schreiner and an introduction by Edmund Bourke. Authors include the heads of dialysis registries for Japan, Europe, and the United States, as well as protagonists of dialyser reuse and short dialysis times. Enthusiasts championed the determination of adequacy of dialysis by formulae or by clinical assessment. All chapters are direct and forceful. The reader will be able to judge the data on what are key controversies in planning dialysis protocols and schedules.

Because of many advances in medicine and biotechnology, an increasing number of individuals are surviving into old age, and we are now challenged to apply sophisticated medical knowledge to the care of the elderly citizen. In nephrology, individuals older than 65 are the fastest-growing group of patients requiring dialysis. Similarly, in increasing numbers, elderly persons present themselves with renal complaints to their family doctor, the geriatrician or the nephrologist. In August 1998, with the financial support of the John A. Hartford Foundation, leaders in geriatrics, nephrology and urology met in Jasper, Alberta, for one week to discuss their areas of special knowledge and to learn from each other. Geriatricians learned from nephrologists, nephrologists learned from geriatricians, and both came to see that they had much in common. All participants discovered a common interest, challenge and commitment, namely, to provide the best renal care to a progressively aging population and to teach their fellows the principles of the other collaborating specialties. This book contains all the papers presented at this meeting and also the text of group discussions on Training and Education, Special Clinical Problems in Geriatric Patients, and Recommendations in Basic and Clinical Research. Nephrology and Geriatrics Integrated will prove useful to both nephrologists and geriatricians in their efforts to manage the renal complaints of the elderly, who come to them in increasing numbers.

The 1991 International Yearbook of Nephrology is the third in a sueeessful .eries whieh has, as its principal aim, thc presentation of a eomprehensive list of topfes of the greatest current relevanee to elinieal nephrologists. We believe that, by following the subjeets eovered by the Yearbook in the broad field of nephrology, the praetieing nephrologist and nephrologist-in-training ean stay abreast of a number of rapidly advaneing fields. To improve the quality of the Yearbook, we have appointed an Editorial Board to provfde suggestions for topies and authors. Thus, we have invited 58 outstanding nephrologists from around the world (the list of them is included in this issue of the Yearbook) to identify annually potential topies for the Yearbook. The reply was exeel lent and the contribution quite outstanding. Thus, for the 1992 Yearbook, we reeeived more than 150 suggestions. A number of them will be included in the next issue if they continue to be viewed as eurrent and important. We also invite readers to suggest topies for upeoming issues of the Yearbook. The present issue, the 1991 Yearbook, represents an improvement over previous volumes. We expeet this trend to be maintained in future years. As in previous issues, all ehapters provide a eomplete, aeeurate and up-to-date list of important references. We are grateful to all the authors for their exeellent eontributions and for having fulfilled the deadline in forwarding their manuseript. Our special thanks to Kluwer Aeademie Publishers for the timely publieation of this volume."

This volume is the first of a biannual series entitled Contemporary Nephrology. The series intends to provide the reader with a broad, authoritative review of the important developments that have occurred during the previous two years in the major areas of both basic and clinical nephrology. We have been fortunate to enlist a distinguished group of scientists, teachers, and clinicians to serve as members of the Editorial Board of this series. We are grateful to them for the outstand- ing contributions they have made to this first volume of Contemporary Nephrology. This volume has fifteen chapters. The first four chapters deal with more basic aspects of nephrology: Membrane Transport (Schafer); Renal Physiology (Knox and Spielman); Renal Metabolism (School- werth); and Renal Prostaglandins (Dunn). Chapters 5-10 are more pathophysiologically oriented, and each contains an "appropriate mix" of basic and clinical information. This group of chapters includes Acid-Base Physiology and Pathophysiology (Arruda and Kurtzman); Mineral Metabolism in Health and Disease (Agus, Goldfarb, and Was- serstein); Hypertension and the Renin-Angiotensin-Aldosterone Axis (Williams and Hollenberg); Immunologically Mediated Renal Disease (Glassock); Acute Renal Failure and Toxic Nephropathy (Anderson and Gross); and the Kidney in Systemic Disease (Martinez-Maldonado). The last five chapters, which are more clinically oriented, include Uremia (Friedman and Lundin); Nutrition in Renal Disease (Mitch); Dialysis (Maher); Renal Transplantation (Strom); and, finally, Drugs and the Kidney (Bennett).

Pocket Reference to Renal Anemia, Second edition, provides a comprehensive overview of anemia in patients with renal disease, including the definition and causes of renal anemia, current management approaches, and the latest clinical practice guidelines. Key learning points are highlighted throughout the book and also listed at the end of the book for a quick reference. The book is useful for general physicians, fellows, and other healthcare professionals wishing to learn more about renal anemia.

"Endourology" provides a summary of the different endourological modalitites, especially the more advanced and controversial techniques, such as the antegrade resection of urethral valves, the transperineal I 125 seed implanations, the spoonloop resectoscope, flexible endoscopy, teflon injection to correct vesicoureteral reflux, stone manipulation in calyceal diverticula, as well as the extraperitoneal pelvioscopy. These techniques are supported by descriptions of the standard endourological procedures.

The presence of Chronic Kidney Disease (CKD) increases the risk of death from cardiovascular causes and makes the management of heart failure difficult. The coexistence of CKD and heart failure is increasing in prevalence worldwide and requires a unique and subtle approach to patient management. Managing the Kidney in Heart Failure focuses on the therapeutic management of cardio renal patients. Common heart and kidney failure conditions are presented along with treatment scenarios aimed to reduce cardiovascular mortality and preserve kidney function. Co-authored by a Nephrologist and Cardiologist, each chapter of this concise and practical handbook offers a unified perspective to these chronic conditions.

We are pleased to present to our readers the proeeedings of the Seeond Bari Seminars in Nephrology. The topie of theses proeeedings deals with elinieal and experimental aspeets of aeute renal failure. The Bari Seminars in Nephrology were initiated in 1984 and will be held every two years. It is attended by a large number of international elinieal seientists in the diseiplines of nephrology and related fields. The next Bari Seminars in Nephrology will take plaee dur i n g Ap r i 1 2 0 - 2 4 i n 1 988 'a n d t he t he m e 0 f t he ga t her i n g w i 1 1 be Drugs, Systemie Diseases and the Kidney. \\e are indebted for the generous finaneial support of the Centro Nazionale delle Rieherehe, Italy. Alberto Amerio Pasquale Coratelli Vito M. Campese Shaul G. Massry vii CONTENTS I. PATHOPHYSIOLOGY AND STRUCTURAL CHANGES OF ACUTE RENAL FAlLURE Pathogenesis of Acute Renal Failure 3 M. Burnier and R. W. Schrier Structural-Functional Correlates in Acute Renal Failure . . . . . . 15 G. Eknoyan, D. C. Dobyan, and R. E. Bulger Long Term Clinical and Morphological Evaluation of Acute Renal Failure . . . . . . 27 V. Bonomini, A. Vangelista, G. Frasca, S. Stefoni, M. P. Scolari, and G. Feliciangeli The Role of Renal Biopsy in Acute Renal Failure . . . . . . . . . . 35 G. D'Amico, G. Colasanti Catabolism in Acute Renal Failure: Importance of Glucocorticoids and Lysosomal Enzymes . . . . . 41 A. Heidland, R. M. Schaefer, J. Weipert, E."

The 6th triennial meeting of the International Study Group for Tryp- tophan Research (ISTRY) was held May 9-12, 1989 in Baltimore, Maryland (USA). From the wide variety of topics and disciplines represented, as documented in this volume, it is clear that tryptophan research and ISTRY are alive and well. ISTRY traces its or1g1ns to at a tryptophan symposium organized in 1971 by H. Schievelbein at Hohenried near Munich (Germany). Up to that time there had been occasional international tryptophan conferences at irregular inter- vals. A number of participants at the Hohenried meeting felt that an inter- national tryptophan organization should be formed to organize regular meet- ings and to foster collaboration and information exchange on tryptophan-re- lated topics. Thanks mainly to the founding work of H. Schievelbein and W. Kochen, an executive committee was elected and ISTRY was born. The inaugural meeting in 1974 was held in Padova (Italy) to honor L. Musajo, one of the foremost pioneers in tryptophan studies. This first ISTRY meeting was suc- cessfully organized by L. Musajo, G. Allegri, A. De Antoni, and C. Costa, and was critical in assuring the viability of the new organization. Subsequent meetings were held in 1977 in Madison, Wisconsin (USA), organized by R.R. Brown, D.P. Rose, and W.E. Knox, honoring C.P. Berg; 1980 in Kyoto (Japan), organized by O. Hayaishi, R. Kido, Y. Ishimura, T. Deguchi, T. Hino, T.

III. International Symposium on Peritoneal Dialysis

There has been a growing awareness that nephrotoxicity represents a key factor in human nephropathies, where, irrespective of the causative agent, only a few clinical end-effects are diagnosed. Thus nephropathies are generally classified as acute or chronic renal failure, malignancies or immunological changes. The weaknesses in diagnosing nephropathies arises because of the effective role the kidney plays in maintaining homeostasis, despite the fact that it has been extensively damaged. The frequencies of some type of chemically-induced acute renal failure is well documented, but the causes of chronic renal failure, malignancy, and other nephropathies are far more difficult to associate with a chemical aetiology. Many of the new therapeutic agents have important beneficial effects, but they are found to have marked nephrotoxic effects. Thus there is a growing urgency to increase the stringency of chemical safety evaluation for their potential nephrotoxic effects. This is strongly countered by the increased financial pressure to identify potentially nephrotoxic chemicals earlier in their development and humanitarian considerations to more closely relate animal test to the clinical situation. Part of the challenge may be achieved by the increasing use of in vitro techniques.

Volume 4 of Contemporary Nephrology summarizes major advances in 16 different areas of nephrology during the years 1985 and 1986. Major changes in the composition of the Editorial Board and authorship of the different chapters have occurred in this volume. Six distinguished contributors have retired from the Editorial Board. They include Dr. Zalman A. Agus, Philadelphia; Dr. Robert Anderson, Denver; Dr. Eli Friedman, Brooklyn; Dr. Richard Glassock, Torrance, California; Dr. James Schafer, Birmingham, Alabama; and Dr. Gordon Williams, Bos ton. We are grateful to them for their outstanding contributions to the of this series and for their advice and suggestions as first three volumes members of the Editorial Board. They certainly deserve substantial credit for the success of this series. Seven outstanding academicians have joined the Board. They in clude Dr. Vito M. Campese, Professor of Medicine at the University of Southern California, who contributed the chapter on "Recent Advances in the Role of the Renal Nervous System and Renin in Hypertension"; Dr. William G. Couser, Professor of Medicine and Head of the Division of Nephrology at the University of Washington in Seattle ("Immunologic Aspects of Renal Disease"); Dr. Garabed Eknoyan, Professor of Medicine and Vice Chairman of the Department of Medicine at Baylor College of Medicine ("The Uremic Syndrome"); Dr. H. David Humes, Associate Professor of Medicine and Chief of the Nephrology Section at the Uni versity of Michigan Medical School, Veterans Administration Medical Center ("Acute Renal Failure and Toxic Nephropathy"); Dr."

LOUIS TOBIAN There are many reasons for suspecting that the medulla of the kidney is involved in the pathogenesis of hypertension. Although our present knowledge does not permit the assignment of a precise and exact role for the medulla, there are so many indications of its involvement that this is an appropriate time for the subject to be thoroughly reviewed, as Drs. MandaI and Bohman have done in this volume. The involvement of the renal medulla in hypertension was first strongly indicated by the studies of Eric Muirhead. Studying renoprival hyperten sion, he demonstrated that the injection of extracts of renal medulla could prevent this type of hypertension in the dog, rabbit, and rat. Subsequently, a number of experiments showed that implants of renal medulla could not only prevent renoprival hypertension but also greatly reduce the level of blood pressure in Goldblatt hypertension in the rat and rabbit. It was later noted that the majority of the surviving cells in these medullary implants were interstitial cells. Pitcock and Muirhead were able to culture these interstitial cells, and implants of the cultured cells lowered blood pressure in renoprival hypertension and Goldblatt hypertension, particularly in the rat. We were able to confirm these general observations by employing implants of medulla in "postsalt" hypertension. The medullary implants did indeed bring the blood pressure down."

Over the last few years, transplantation knowledge and techniques, as well as insights into pharmacology, have improved, thus enabling greater access to transplantation for patients. The pool of organs for transplantation is stable, and therefore insufficient to cope with the growing demand. To adjust demand and resources in the most equitable way, organ procurement and allocation have been organized nationally and often across borders. The national and international organ exchange programs were studied and discussed during the Congress on Organ Allocation, from which this book is derived. This book describes the state of the art in the management of waiting lists and the allocation of organs in transplantation. It includes chapters on the possibilities of expanding the pool of available cadaver organs. It also analyzes the results of transplantation of cadaver organs from older donors and marginal, non-heart beating donors. Transplantation policies based on the offering of organs by living donors are also described, as is the impact of delayed graft function on organ allocation.