This book is intended for use by nephrologists, internists, hospitals, trainees in these specialties and indeed anyone interested in renal medicine. It contains top-class authoritative and up-to-date reviews by internationally renowned experts coming from some of the best nephrology centres in the world. It covers the diagnosis, causes and management of acute kidney injury. It also includes a discussion of the diagnosis of chronic kidney disease, including the use of simple clinical and laboratory data, imaging, proteinomics and renal biopsy. It reviews the general management of chronic kidney disease, including an in-depth analysis of kidney transplant immunology. This book is therefore a comprehensive, authoritative text with clear explanation of even the most complex topics.

Recent developments in recombinant DNA technology have led to the large-scale production of human erythropoietin and to the demonstration that it is effective in the treatment of renal and possibly some other anaemias. This has lent a new impetus to studies of the pathophysiology and pharmacology of the hormone which is reflected in this report of the proceedings of a meeting held in Liibeck in June 1988. In 15 papers, all from European centres, the broad topics covered are erythropoietin's physiology and chemistry, the patho- physiology of erythropoiesis and the use of erythropoietin in the treatment of anaemia. Several of the papers include up-to-date reviews of the literature. The field is now expanding rapidly, and this volume, though not comprehensive, usefully points up many areas of recent understanding as well as others of continuing un- certainty. Overall, it contains material likely to be of interest to biochemists and experimental haematologists as well as to phar- macologists, clinical haematologists and nephrologists.

This book provides a comprehensive look at renal cell carcinoma, exploring its biology as well as current and future molecular targets for renal cancer carcinoma.

The Department of Continuing Education of Harvard Medical School and members of the faculty of Harvard Medical School held a multidisciplinary course on the management of patients with urologic cancer in the fall of 1982. This course high lighted the multidisciplinary approach to the care of these patients, and outlined the clinical and pathophysiological basis for diagnosis and treatment. The term multidisciplinary was essential to the course in which the disciplines of uro logic surgery, medical oncology, and radiation therapy were each appropriately emphasized. Widespread interest in the contents of this course, and the timely and useful nature of much of the information presented there, has encouraged us to publish, in as rapid a manner as possible, new information and highlights of that course. A camera-ready format was used to allow rapid production, and a variety of disparate styles were maintained from chapter to chapter--some in prose, others in outline. Again, our intent was to disseminate information rapidly and accurately, and to that end, we felt that consistency of style was irrelevant."

When Shaul Massry and Herbert Fleisch asked me to write a foreword for this book, I was honored and eagerly looked forward to reading the many chapters. As they came and I skimmed through them, my mind wandered back to the earliest classic contributions in this field in the late 1920s and early 1930s by Albright and his associates, Greenwald and Gross and Adolph, on the homeostatic regulation of inorganic phosphate and the central role of parathyroid hormone (PTH) in this regulation. They clearly showed the exquisite sensitivity of the renal handling of phosphate to varying dietary and parenteral loads and to changes in the level ofPTH. That two outstanding investigators in the field of divalent ion me tabolism should choose to edit a book solely about the renal handling of inorganic phosphate shows how far we have progressed from these early classics to the recent almost exponential increase in the research and publications related to this subject. Despite this increase, I asked myself, is such a large new monograph, consisting of 13 chapters and 30 distin guished authors, warranted? My reading of these chapters and my learning so much from them convinced me that it is, and my pride was heightened in being asked to write the foreword for this book."

Nitrates have been for many years the cornerstone of cardiovascular therapy for various indications. Not only have nitrates stood the test of time for treatment of chronic stable angina pectoris, but the indications for them have markedly ex panded. They now include all forms of angina pectoris and myocardial ischemia, congestive heart failure and hypertensive emergencies. The beneficial effects of nitrates in all these conditions result from their vasodilatory properties, but it is still unclear whether the central or peripheral effects predominate in the thera peutic mechanism. Recently nitrates have been shown to fulfill the most important requirement for each and every drug - to reduce mortality. A large scale study revealed that isosorbide dinitrate, combined with hydralazine, reduced long-term mortality by 28% in patients with congestive heart failure. This finding will certainly stimulate research on nitrates, and it might be expected that interest in these drugs will markedly increase. The primarily used nitrates in clinical practice are nitroglycerin and the com plex organic nitrates, mainly isosorbide dinitrate. The organic mononitrates are now under clinical investigation, and isosorbide-5-mononitrate (IS-5-MN) appears to be especially promising.

The Fourth International Congress of Peritoneal Dialysis was held in Venice, Italy, June 29 to July 2, 1987. By this time peritoneal dialysis had emerged as a treatment for a substantial fraction of patients with end-stage renal disease and countless numbers of patients with acute renal failure. This treatment is now practiced worldwide and is the life-sustaining treatment for about 40,000 patients with chronic renal failure, representing 15 to 20% of dialysis therapy in about 1000 centers. It is not surprising, therefore, that the number of health professionals engaged in the investigation and the application of the treatment has also grown exponen tially. The First International Symposium on Peritoneal Dialysis, organized by Dr. A. Treviiio-Be cerra in Chapala, Mexico, in 1978, brought together a group of pioneers when continuous ambulatory peritoneal dialysis was in its infancy. In 1981, Dr. G. M. Gahl chaired the Second Symposium, in West Berlin, when the technique and professional interest were growing con siderably. By 1984, when Dr. 1. F. Winchester and I organized the Third Symposium, the pre sented papers exceeded 100 and there were about 1000 attendees. At that time, it was deemed appropriate to form a more organized group and the International Society for Peritoneal Dialy sis was founded. One of the first actions of the Society was to choose from among several applicants Dr."

This volume emphasizes the comparative approach to under standing vertebrate renal function. I am convinced that this approach is of particular value in understanding both the details of renal function at the cellular and subcellular levels and the renal role in regulating fluid volumes and solute concentrations. My exposure to this approach first occurred during a student research experience in the laboratory of Wilbur H. Sawyer, who also provided an introduction to the works of Homer W. Smith and August Krogh. The importance of this approach was reinforced by doctoral and postdoctoral research in the laboratory of Bodil Schmidt-Nielsen. It has been confirmed through years of personal experience since then. My research and my understanding of renal function have been aided through the years by collaboration and discussion with numerous students and associates. Of particular impor tance in developing my views on comparative renal function, and especially on the relationship of structure to function, has been my long association with my colleague and friend, Eldon J. Braun. Donald S. Farner, who suggested the writing of this volume, provided valuable editorial assistance. Much of my personal research in this area has been supported over the years by grants from the United States National Science Foundation and National Institutes of Health. The writing of this volume was completed while I was in Wiirzburg, Federal Republic of Germany, supported by a Senior U.S. Scientist Award from the Alexander von Humboldt Foundation."

The kidney, similar to the heart, plays a three-fold role in essential hypertension. First, it participates in the patho genesis of arterial hypertension. Second, it suffers as a target organ of long-standing hypertension, and third, it experiences the effects of antihypertensive therapy. Perhaps most contested at the present time is the involvement of the kidney in the patho genesis of essential hypertension. More than a century ago, William Osler put forward three basic hypotheses about the "genuine contracted kidney. "l 1. "The hypertrophy can be regarded as an effect to overcome a sort of stop-cock action of the vessels when under the influence of an irritating ingredient in the blood greatly contracted and increased the peripheral resistance. " Clearly this hypothesis of an "irritating ingredient" is perhaps the most convincing nowadays, and numerous attempts have been made to identify a specific vasoconstrictive agent in the blood in essential hypertension. 2. "The obliteration of a large number of capillary territories in the kidney materially raised the arterial pressure. An additional factor of dimin ished excretion of water also heightened the pressure within the blood vessel. " Today we know that fluid volume overload in the presence of reduced renal mass seems to be the most likely mechanism accoun ting for renal parenchymal hypertension and, as shown by Guyton's group, for certain forms of experimental hypertension. 3.

The focus of this book is to provide a nephrology reference manual for the developing pediatrician and pediatric nephrologist. Its objective is not only to inform but also to teach -- one that inspires thinking in the reader. The contents and level of teaching in the manual are intended for trainees at four different levels: medical student, intern, resident and fellow. This handbook provides what other nephrology textbooks cannot -- a useful and practical guidebook that is written to teach at a level that is appropriate for various stages of learning. Each chapter focuses on a specific topic, followed by several patient cases, and with an answer and discussion of each case.

The management of chronic renal failure by dialysis and transplantation has now become an established form of treatment in many parts of the world. However, these forms of treatment have brought with them problems in relation to the selection of patients, economics, clinical problems such as hypertension, encephalopathy, anaemia and renal bone disease, and psychological and social problems. The management of haemodialysis has changed over the years with developments in dialysers, vascular access and the duration of dialysis. Although the overall survival from renal trans plantation has changed little in the past four or five years, there are hopes of improvements in relation to tissue typing and enhancement. Perhaps the most important aspect in the management of chronic renal failure is the multi-disciplinary approach. Nursing and medical staff work closely with dialysis technicians, engineers, dietitians, local authority per sonnel, social workers and with the relatives of the patients. The symposium was planned to draw together representatives from all disciplines involved in the care of patients with chronic renal failure. One of the most relevant sessions was that in which two patients with chronic renal failure described their experience."

Vittorio E. Andreucci of keeping alive patients in terminal chronic Initially created with the purpose renal failure, dialysis has undergone improvements in methodology, and its final goal has become complete health rehabilitation and optimization of the quality of life of chronic dialysis patients. To achieve this, many investigators have attempted to increase dialysis efficiency and at the same time shorten dialysis time. Their main concern was, obviously, patient safety: the Latin proverb 'primum non nocere' is still valid all over the world. Thus, when clinical observations of the first patients on regular dialysis therapy suggested an inverse relationship between duration of dialysis sessions and severity of peripheral neuropathy, long and frequent dialysis sessions were considered the only way to prevent the catastrophic consequences of nerve damage and underdialysis syndrome. It was then, in 1971, when dialysis duration was 8- 12 hours per session, that Vincenzo Cambi started a 'short dialysis' trial, i. e. , 4 hours 3 times weekly or 3 hours every second day. For the first time, dialysis was shortened from 24-36 hours weekly to 10. 5-12 hours weekly [1, 2]. In 1971 I was still at the Parma University Hospital. We had both just returned from the United States, and Dr. Cambi was responsible for the dia lysis unit.

Gabriel of Urantia asked the question, in the beginning of his struggle with dialysis, "God, why is this happening to me?" Throughout his 8-month dialysis experience, 3 days a week, 4 hours a day, being tied down to a chair while his blood flowed from his body through a machine and back, he realizes-from the people he meets also on dialysis and in the hospitals after post-kidney-transplant-that very bad things happen to very good people. He met young and old alike, tied down to the machines just like he was, and the young people were the hardest for him to resolve in his mind with God and also to try to give them hope. As a minister, he felt obligated to do so. Being a Pastor of a church (Global Community Communications Alliance-a very social, environmental, and spiritual activist church), he knew that bad things happened to good people who try to change the world. But this disease is personal, between him and God you might say. So he had to discover for himself why God allowed this to happen to him and to the other very good people he met with various traumatic illnesses in the hospitals and dialysis centers. Gabriel of Urantia tries to explain how he felt along the path, from the beginning to the receiving of his new kidney from his 22-year-old daughter and gaining the hope and health to continue not only his spiritual work, but his work as a musician, guitar player, and singer (in which he was planning a tour around the country with his 11-piece Bright & Morning Star Band), while now taking immunosuppressant drugs to keep him alive. He had all the fears that a new transplant patient has. How long will the kidney last? What other affects do these drugs have on my body? He writes about his experience with the medical world, the services he experienced from both very qualified people and those not so qualified (experienced and inexperienced care givers), as well as the bureaucracy of the medical field and insurance companies (both private and governmental). He realized that often in the medical field, the right hand didn't know what the left hand was doing and the patient suffered the results. Beyond that, Gabriel of Urantia tries to give hope to people with life-threatening illnesses by sharing his faith in the Creator to all who may read his book. A must-read for anyone on dialysis or with any life-threatening illness, from a writer who went through this and can identify with what they are going through and give them hope through this trauma in their lives.

A large number of chemical agents are known which affect blood and blood-forming organs. The purpose of this volume is to review the sig- nificant advances made over the past several years regarding such chemical agents. The purification, biological action, and therapeutic implications of several widely used hematopoietic growth factors such as interleukin 3 (IL-3 or multi-CSF), granulocyte/macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), colony stimu- lating factor (CSF-I or M-CSF), thrombopoietin, and erythropoietin are included in this volume. These factors are important in regulating several hematopoietic cell lines such as neutrophils, monocytes, eosinophils, macrophages, megakaryocytes, platelets, and erythrocytes. People are exposed daily to numerous toxic chemical substances present in our environment which produce a suppression of erythropoiesis, myelo- poiesis, lymphocytopoiesis, and megakaryocytopoiesis. Attempts have been made in this volume to assess the therapeutic role of some of the hematopoietic factors such as erythropoietin in the anemia of end stage renal disease, as well as colony stimulating factors in other hematopoietic abnormalities. In addition, some of the chemical factors in our environment which suppress major hematopoietic lineages stimulated by erythropoietin, macrophage colony stimulating factor, granulocyte colony stimulating factor, interleukin I-alpha, interleukin I-beta, and interleukins 2, 3, 4, 5, 6, 7, and 9 are also included. An updating of the mechanism of action of each of these factors on the major hematopoietic lineages is covered.

The European School of Oncology came into existence to respond to a need for information, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons why such an initiative was considered necessary. Firstly, the teaching of oncology requires a rigorously multidiscipli nary approach which is difficult for the Universities to put into practice since their system is mainly disciplinary orientated. Secondly, the rate of technological development that impinges on the diagnosis and treatment of cancer has been so rapid that it is not an easy task for medical faculties to adapt their curricula flexibly. With its residential courses for organ pathologies and the seminars on new techniques (laser, monoclonal antibodies, imaging techniques etc.) or on the principal therapeutic controversies (conservative or mutilating surgery, primary or adjuvant chemotherapy, radiotherapy alone or integrated), it is the ambition of the European School of Oncology to fill a cultural and scientific gap and, thereby, create a bridge between the University and Industry and between these two and daily medical practice. One of the more recent initiatives of ESO has been the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on future developments in specific fields of on cology."

One person in four in the industrialized countries suffers from hyperuricemia and is therefore at risk of developing gouty arthritis, nephrolithiasis, or any of the other consequences of urate deposition. At present, far too little is known about urate deposition and the mechanisms by which it occurs, as well as about its clinical consequences, which include formation of toph; over the helix of the ear or in bones close to joints that have never exhibited an attack, development of bursitis, chronic tendovaginitis leading to carpal tunnel syndrome, and gouty paraplegia. Information on these matters is needed to estimate the risks of hyperuricemia and to determine when therapeutic intervention is indicated. The contributions and discussions in this book, resulting from an international symposium held in December 1990 in the Medizinische Poliklinik in Munich, provide an up-to-date source of current knowledge about hyperuricemia in man and its clinical consequences.

Congenital adrenal hyperplasia (CAH) consists of a group of disorders of adrenal steroidogenesis. Each disorder results from an inherited deficiency of one of the several enzymes necessary for normal steroid synthesis. The different enzyme deficiencies produce characteristic patterns of hormonal abnormalities; the clinical symptoms of the different forms of CAH depend on the particular hormones that are deficient or that are produced in excess. The earliest documented description of CAH was by DeCrecchio in 1865 (DeCrecchio 1865). This Neapolitan anatomist described a cadaver having a penis with first degree hypospadias but no externally palpable gonads. Dis- section revealed a vagina, uterus, fallopian tubes, ovaries, and markedly enlarged adrenals. It is interesting that the subject suffered a confusion of sex assignment, being declared a female at birth and a male 4 years later. He conducted himself as a male sexually and socially. Since the original descrip- tion of this case, investigators have unravelled the pathophysiology of the inborn errors of steroidogenesis. 1 Steroidogenesis and Enzymatic Conversions of Adrenal Steroid Hormones A. Steroidogenesis The adrenal synthesizes three main classes of hormones: mineralocorticoids (17-deoxy pathway), glucocorticoids (17-hydroxy pathway), and sex steroids.

Heart and brain interaction is an increasingly vital area of clinical investigation. This is the most comprehensive review of the subject available, presented by internationally recognized authorities in the field. The book offers extensive coverage of cardioembolic stroke, including a brand new contribution on the mechanism of hemorrhagic infarction. Controversial topics such as anticoagulation, combined carotid and coronary surgery and screening for silent coronary disease are covered. Also included are a comprehensive review of the cardiovascular/neurobiological role of the central nervous system in hypertension and sudden death, and a practical approach to the patient with syncope. This integrated, topical presentation makes essential reading for neurologists, cardiologists, internists and anyone caring for patients with stroke or cardiac disease.

For more than a century, the condition now known as Idiopathic Hydronephrosis has been recognised as a clinical entity, and following the original description by Rayer in 1841 a variety of procedures were devised in attempts to correct the condition surgically. Most of these early methods were introduced in the last decade of the nineteenth century by several illustrious clinicians, including Trendelenburg, KOster, Fenger and Sutton. For many years diagnosis was based purely upon the patients presenting signs and symptoms and not until the early part of this century was technology available to assist in the pre-operative diagnosis of the condition. Early methods depended upon radiological techniques, and the introduction of the retrograde pyelogram by Voelcker and Lichtenberg in 1906 represented a significant advance in diagnostic methodology. Other methods also dependent upon radiographic techniques were subsequently introduced, including urography in the late 1930s by Swick, and more recently, the method of cineradio graphy, as pioneered with considerable success by Peter Narath in the decade following World War II. During the past 50 years a variety of surgical procedures have been introduced for the treatment of idiopathic hydronephrosis. That so many different methods have been devised suggests that no one specific technique is capable of achieving a complete cure in all cases."

Glomerulonephritis has always been regarded as a complex subject. Different forms o f the disease c a n cause death in a matter o f weeks, nephrotic syndrome which might or might not prove responsive to steroid therapy, or no symptoms a t all. Improved pathological te- niques and criteria have permitted a more accurate diagnosis and prognosis to be established for many patients. With increased und- standing of the immunological mechanisms involved it has become apparent that many patients presenting with a variety of symptoms and signs m a y have glomerulonephritis as their primary pathological process. This book examines the clinical, pathological and aetiological factors involved in the common forms o f glomerulonephritis. Each chapter has been written by a recognized expert in the field and provides information of relevance and practical importance to the average clinician. The developments of the last decade have emp- sized that glomerulonephritis is no longer a matter only for the nephrologist but a subject o n which all clinicians should be well informed.

Almost every practising doctor will admit to difficulty in knowing how best to investigate, treat and advise the pregnant patient with renal problems. These doubts and difficulties may be exacerbated if the patient seeks pre-pregnancy advice - would a possible pregnancy cause a deterioration in renal function, what are the risks of the pregnancy for mother and baby? As the general public become more informed on medical matters these questions are being asked more frequently and doctors must be prepared to offer advice which is based on detailed factual knowledge. This book examines some of these increasingly common clinical problems. Each chapter has been written by a recognized expert in the field and provides the type of specific information now expected by discerning patients. The advances in treatment of the last decade clearly indicate that a knowledge of pregnancy and renal disorders is essential for doctors in many branches of medical practice.

Renal stone disease remains a common clinical problem. Patients m a y attend either medical or surgical clinics and n o t infrequently present as acute abdominal emergencies to general practitioners, physicians, surgeons and even gynaecologists. Recent urinary calculi continue to cause considerable morbidity despite the recent advances in our understanding of the pathogenesis of the different types of stones involved and despite improvements in t reatment- by appropriate drug therapy, by ultrasound techniques and by lithotripsy. This volume discusses the investigation and management o f patients with calculus disease. Each chapterhas been written by a n experienced clinician and provides information of considerable relevance and importance for all doctors engaged in clinical practice. The technical developments o f the last few years have clearly demonstrated that renal stone disease, even when recurrent, should be an uncommon cause of chronic renal failure. Knowledge o f the recent developments in this field is important for all practising doctors and even more important for their patients.

CHARLES Y. c. PAK Major progress has been made in the pathophysiologic elucidation and management of nephrolithiasis during the past two decades. It is now possible to detect the cause of stone disease in more than 95% of patients, to prevent recurrent formation of stones in the majority of patients, and to remove most existing stones less invasively. The assumption of editorship of this book permits me to indulge in the discussion of this progress from my personal perspective. Three somewhat fortuitous events in my academic career dictated my directing major efforts in stone research. The first event occurred in 1963 when, after having completed medical training, I was faced with two years of military service as a participant of the Berry plan. Choices were limited and disconcerting for someone interested in a research career: a staff physician at a military installation or an indian reservation, or a member of a research team in a state penitentiary. An interesting article by Norman Gershfeld on phospholi pid monolayers prompted me to write him seeking a position in his laboratory of Health (NIH) in Bethesda, MD. Partly because of at the National Institutes my rudimentary exposure and publication in surface chemistry, I was offered a position as a staff scientist and a position in the Public Health Service which satisfied the requirements of a military service."

The action of diuretics including cellular mechanisms of action, pharmacokinetics, and clinical usage, with much emphasis placed on the most recent findings on the pharmacodynamics of the respective drugs. During the past twenty-five years since volume 14 on Diuretica was published in the Handbook series, the cellular mechanisms of action of diuretics have slowly been unravelled. Today, the role of action within the target cells is known for most of the substances discussed. This has provided a new basis not only for the understanding of drug action but also for secondary effects and interactions. The book represents a comprehensive reference work on the diverse groups of diuretics which are among the most frequently prescribed medications.

Combining principles of contemporary immunology with applications to immunopathology, this up-to-date volume documents new developments in the understanding of the origin of autoimmune diseases. Emphasized are cellular and molecular approaches in both organ-specific and systemic autoimmunity. A comprehensive bibliography, numerous illustrations, and tables make it an invaluable source of information for immunologists, rheumatologists, pathologists, dermatologists, and nephrologists.