The need for adequate means by which to improve urine output is very old. Even in the "Scuola Salernitana", the oldest medieval medical school in Western Europe, about 1000 years ago it was taught how to improve urine output. The list of known "diuretica" included herbs, plants, roots, vegetables, in particular asparagus, fennel and carrot. The first diuretic drugs, however, were mercurial compounds. Thus, calomel, mercurous chloride, was initially used as a diuretic in the sixteenth century by Paracelsus, being one of the ingredients of the so-called "Guy's Hospital pill". But calomel had a cathartic effect so that it was replaced by organic mercurial compounds. These diuretics were clearly toxic. After the discovery of the car bonic anhydrase, in the early 1930s, and the introduction of sulfanilamide as a chemotherapeutic agent, it was observed that this drug was inhibiting carbonic anhydrase in vitro and urinary acidification in vivo thereby causing metabolic acidosis; urine output, however, appeared to increase. Subsequent studies led to the synthesis of more potent analogs, in particular acetazolamide. Studies on car bonic anhydrase inhibitors led to the synthesis of benzothiadiazides which disclosed much less inactivating action on carbonic anhydrase and much more diuretic effect through an inhibition of tubular transport of sodium and chloride. Chlorothiazide was the first member of this class of diuretics. Thiazides are still used in clinical practice.

When the external Quinton-Scribner arteriovenous shunt was developed in 1960, and, a little later, the internal Brescia-Cimino arteriovenous fistula was developed as a vascular access for hemodialysis, thereby making possible regular dialysis therapy of chronic uremic patients, many nephrologists became surgeons, having learned the type of vascular surgery related to hemodialysis quite well. The same series of events occurred with regards to peritoneal dialysis with the introduction of the Tenckhoff catheter and the need for gaining a permanent access to the peritoneum for chronic ambulatory peritoneal dialysis (CAPD) therapy. With time, however, problems relating to vascular and peritoneal access have forced many nephrologists to give up their surgery; meanwhile, many surgeons have become quite expert in some sophisticated techniques relating to dial ysis (e. g., vessel grafting, prosthesis implantation, etc.). Today, whether or not involved in this type of surgery, both nephrologists and surgeons remain interested in knowing all available access devices for dialysis as well as the surgical techniques involved. However, all nephrologists involved in dialysis must know how to prevent or treat complications related to dialysis access. Thus, it appeared to me to be quite advisable to have a book in my series, Topics in Renal Medicine, dealing with vascular and peritoneal access for dialysis.

During recent decades, it has been firmly documented that chlamydiae are com mon and important pathogens in humans and animals. In humans, chlamydiae are known to cause trachoma (which is still one of the major blinding diseases in the world) and are also one of the most common etiological agents of sexually transmitted diseases and the sequelae thereof, such as infertility. In the last few years, it has also become evident that chlamydiae, i.e., the so-called TWAR agents, are common respiratory tract pathogens. Chlamydiae are also important pathogens in birds and lower mammals, in whom they cause a variety of infectious conditions, a spectrum which has in creased every year. Some of these infections occur as zoonoses, e.g., psit tacosis/ornithosis and, as recently discovered, abortion. Know ledge of the molecular biology and immunobiology of chlamydiae has expanded rapidly during recent years. Insight into the pathophysiology of chla mydial infections has also increased, and new methods for the diagnosis of chlamydial infections have been introduced. The importance of establishing control and preventive programs for chla mydial infections has become obvious in order to combat the present chlamydial epidemic. We hope that this book can usefully serve those who want to increase their general knowledge of Chlamydia and that it can act as a handbook and reference source for those involved in chlamydial research as well as for those working with chlamydial infections in medical and veterinary clinical disciplines, includ ing clinical laboratories."

With contributions by D. Albrechtsen, O.H. Bentdal, H. Bondevik, I.B. Brekke, P. Fauchald, J.G. Fjeld, A. Flatmark, A. Foss, A. Hartmann, H. Holdaas, R. Innes, A. Jakobsen, N.E. Klow, B. Lien, O. Oyen, P.F. Pfeffer, K. Rootwelt, G. Sodal and K. Vatne

This is a book about renal cysts and cystic kidneys. Its contributors have created a resource of current information in a field that once aroused only curiosity, but that now stands at the leading edge of molecular nephrology. Its authorship includes 'oldtimers', who bring the wisdom of experience, and 'newcomers', whose presence attests to the contributions made by the investigative and technological advances of the past decade. Its text is organized to carry the reader from renal cyst to cystic renal disease. Each of its chapters defines or explores a challenge or an advance. Cells that line renal cysts are diverse in structure, type, and perhaps function. The cysts themselves lie within an interstitium that is not normal and may influence cyst development and growth. Experimental analogs of human disease offer increasing opportunities to basic researchers to examine, in sequence and under controlled circumstances, those events that favor nephron dilation, cyst growth and ultimate renal failure.

Renal transplantation is now accepted as the treatment of choice for patients with end-stage renal failure. During the last decade both patients and graft survival rates have increased significantly and when assessed at one year are now greater than 90% and 80% respectively. These marked improvements have occurred at a time when increasing numbers of patients in the older age groups and with more complex forms of renal disease are being accepted for transplantation. The reasons for the improved clinical results are not fully understood but are probably linked with changes in blood transfusion policy, tissue typing policy and drug therapy. These topics, together with immunological monitoring and details of how to treat the highly sensitized patient, are fully covered in this volume. All the chapters have been written by recognized experts in their field. Not only are the recent advances well documented but the likely future developments in management are identified and discussed. As renal transplantation is now the single most common of treatment for renal failure, the information presented in this form volume should prove of value to all with an interest in current clinical practice.

This book is a gift from the international community of amyloid friends, presented to Professor Dr. Enno Mandema on the occasion of his retirement from the University of Groningen, the Netherlands. It is the "precipitation" of up to date knowledge of amyloidosis, as presented at the International Course on Amyloidosis in Groningen, on the 10th and 11th of October 1986. Twenty years ago, Professor Mandema invited a group of scientists, who were studying the various aspects of amyloidosis from different points of view, to discuss their mutual interest in the subject. This "First International Symposium" was held for five days in September 1967. It was a wonderful experience for the participants, as most of them had until then only read each others work in the literature. The proceedings of that symposium, which contained the "lively" dis cussions, became a text-book for the following years. Research continued, and while the book was still in preparation, the revolutionary method of "water-soluble amyloid" was published. In the following years, different amyloid proteins were discovered and the mo lecular basis of the different amyloid syndromes was elucidated. The increase in knowledge parallelled the availability of modern, ingenious and also rapid methods in the biomedical sciences."

The year was 1943. As a third-year medical student at Stanford, I was about to witness the beginning of a medical miracle. Dr. Arthur Bloomfield, Professor of Medicine, had selected my patient, a middle aged man, who was dying of acute pneumococcal pneumonia, as one of the first patients to receive miniscule doses (by today's standards) of his meagre supply of a new drug - penicillin. The patient's response amazed everyone especially this impressionable medical student. The rest of the story is history. With one stroke, the introduction of penicillin removed from the medical scene the 'friend of the aged' - lobar pneumonia. The consequences, which no one could have imagined at the time, are still becoming manifest as other 'miracles' such as respirators, artificial kidneys and many potent new antibiotics have come upon the scene. All of us are aware that these miracles have created a variety of new challenges around the states of dying and near dying. We have no easy answers for these problems. Nevertheless as dialysis techniques, especially CAPD, are applied more widely to the treatment of the elderly, the task of helping the patient meet death with dignity becomes increasingly important and vexing because once begun, dialysis is difficult to terminate.

For more than a generation haemodialysis has been the principal method of treating patients with both acute and chronic renal failure. Initially, developments and improvements in the system were highly technical and relevant to only a relatively small number of specialists in nephrology. More recently, as advances in therapy have dem onstrated the value of haemoperfusion for certain types of poisoning, the basic principles ofhaemodialysis have been perceived as important in many areas of clinical practice. In this volume, the potential advantages of bicarbonate haemo dialysis are objectively assessed, the technical and clinical aspects of both haemofiltration and haemoperfusion discussed and the con tinuing problems associated with such extracorporeal circuits analysed. All the chapters have been written by recognized experts in their field. The increasing availability of highly technical facilities for appropriately selected patients should ensure that the information contained in the book is relevant not only to nephrologists but to all practising clinicians."

The Final Report of the USA CAPO Registry summarizes eight years of observation and analysis that reflects the experiences of 485 clinical centers and over 25,000 CAPO patients. As such, it offers a wealth of information, available here for the first time to interested parties around the world. Because the National Institutes of Health was quick to see the potential of CAPO as a promising therapy for patients with end stage renal disease, the Registry project was begun soon after its introduction into clinical practice in the USA. Accordingly, the Registry offered the nephrology community in the United States a special opportunity to study this emerging new therapy in some detail, an opportunity not previously available for any other form of dialysis. As will be seen in this report, the result of this early and intensive research effort has been the development of a vast amount of clinically important information regarding the utilization, safety, and efficacy of this important dialytic therapy.

In June, 1981, we conducted a two day international symposium in Rome devoted to original scientific presentations on arachidonic acid metabolism in the kidney. Scientists from 20 countries were represented either in the general scientific program or in the poster presentation. This book does not represent the proceedings of this international gathering, but rather the edited manuscripts specifically prepared as sum- maries of the scientific presentations. We feel that the timeliness and originality of the contributions as well as the need for a compilation of existing work on prosta- glandins, thromboxane, and the kidney warrant this publication. The meetings would have been impossible without the generous and substantial support of the Italian government, the National Institutes of Health, United States Public Health Service, and Merck Sharp & Dohme International. Supplementary support was also received from Ciba Geigy S. p. A. , Ente Fiuggi, Farmitalia Carlo Erba S. p. A. , Glaxo Laboratori S. p. A. , Hoechst Italia S. p. A. , Leo Pharmaceutical Products, Pfizer Italiana S. p. A. , Sigm? Tau S. p. A. , Squibb S. p. A. , The Upjohn Company, Wellcome Italia S. p. A. , and Burroughs Wellcome Company. The efficient organization of the symposium was largely attributable to the superb efforts of Elisabeth Mutschlechner and Miki Scarinci of C. K. International, Rome. Linda Goldberg provided expert and invaluable editorial and secretarial assistance in the organization of this book. The book is divided into four major sections comprising: I.

Ethical Problems in Dialysis and Transplantation presents an overview of issues with which nephrologists and decision makers are confronted in their daily practice. The search for a universal system of ethics and theories of justice are addressed. Furthermore the work provides a normative ethical discussion of ways of distributing resources with a view to selection and commercialization. Others chapters discuss a philosophical and religious analysis of stopping treatment and the clinical and ethical aspects of stopping treatment in dialysis. Different views from different countries on the subject of dialysis and transplantation are covered including the views expressed by contributors from India, Africa, Japan, Great Britain and China. The work presents the clinician with a guide to the ethical considerations underlying the treatment of dialysis and renal transplantation patients.

A workshop was organised in order to achieve multi-discipli- nary review of the pathogenesis and management of acute failure, particularly as it occurs and is managed in intensive therapy units. The book deals with the realities and practicalities of this important area of acute medicine. Each chapter is followed by a discussion, so that a concen- sus view is obtained from an international body of experts.

Anil K. Mandai, M.D., is one of the trailblazers in the use of the transmission electron microscope in the study of the urinary sediment. In this book, he reviews his extensive efforts to tie his vast clinical expe rience to his elegant basic research with the electron microscope. The pictures are comprehensive, and the clinical correlates are nicely outlined in tables and text. It may astonish some readers that a book for fellows and clinical nephrol ogists has been written on the use of the transmission electron microscope in the study of urine. Some may view this as a sophisticated research instrument. I, however, applaud the effort. So many discoveries and advances in basic science lie unutilized because clinicians are not aware of the tools available or have little instruction in their use. Maybe that is the reason why so many tests have come and gone, have been found useless and dropped, or have simply been abandoned after being judged too complicated-some because they were, others because they were never applied and interpreted properly. The whole field of research seems to be pulling ahead and away from clinical medicine. Therefore, an effort like this one, which rapidly and clearly tries to introduce an advanced research examination technique into clinical medicine, is worthy of admiration and sup port."

Urinary tract infection remains one of the most common reasons for an individual seeking medical advice. Although the associated morbidity varies widely in adults, such infections are less common but may constitute severe, life-threatening illness in children and in the elderly. Diagnostic tests and treatment have been rationalized in recent years but many practising doctors still have difficulty in appreciating the patho-physiological principles involved. Particular difficulty is often experienced when treating patients with recurrent urinary tract infections, covert bacteriuria, vesico-ureteric reflux, elderly patients and those with indwelling catheters. These topics are fully discussed in this volume. Each chapter has been written by a recognized expert and practical aspects of patient management have been emphasized. The information presented in this volume should prove of interest not only to nephrologists but to all practising clinicians. VII ABOUT THE EDITOR Professor Graeme R. D. Catto is Professor in Medicine and Thera peutics at the University of Aberdeen and Honorary Consultant Phy sician/Nephrologist to the Grampian Health Board. His current interest in transplant immunology was stimulated as a Harkness Fellow at Harvard Medical School and the Peter Bent Brighton Hos pital, Boston, USA. He is a member of many medical societies includ ing the Association of Physicians of Great Britain and Ireland, the Renal Association and the Transplantation Society. He has published widely on transplant and reproductive immunology, calcium metab olism and general nephrology."

Therapeutic regimens for visceral leishmaniasis (also Kala-azar, Dum-dum fever or black fever), caused by parasitic protozoa of the Leishmania genus, evolve at a pace never seen before. Spread by tiny and abundant sand flies, the parasite infects internal organs and bone marrow and if left untreated will almost always result in the death of the host. In developing countries successful diagnosis and treatment are complicated by asymptomatic cases, undernutrition and Kala-azar/HIV co-infections.

This book brings together world-renown experts writing state-of-arts review on the progress in diagnosis and treatment of visceral leishmaniasis, ultimately leading to the complete elimination of this fatal disease from South Asia. The chapters provide valuable information for disease control as well as therapy and the diagnostic improvements necessary for early treatment, subclinical detection and drug-resistant cases. The presented methods allow for points-of-care testing in the endemic area, enabling rapid detection in resource-poor settings with easy handling and low costs.

This book provides essential information for scientists, medical practitioners and policy makers involved in the diagnosis, treatment and elimination of Kala-azar.

Conditions such as oxidative stress and hypoxia, which have a generalized impact on the oxygen metabolism, have been implicated in the genesis of kidney disease. This means that deepening our understanding of the pathobiology of oxygen metabolism in such diseases could be a fruitful path towards tangible clinical benefits. Studies in Renal Disorder collects reviews from leading researchers and clinical scientists working in exactly this field, providing an overview of the latest advances. The causal role of impaired oxygen metabolism in kidney disease has numerous clinical implications. It affects our understanding of the therapeutic benefits accruing from anti-hypertensive agents; the way we control hyperglycemia/hyperinsulinemia and hyperlipidemia; and our use of dietary approaches to the correction of obesity. The defensive mechanisms against oxidative stress, such as the Nrf2-Keap1 system, and hypoxia, such as the PHD-HIF system, have recently been explored in various cells, including kidney cells. These mechanisms include intracellular sensors for oxidative stress and hypoxia. This means that novel approaches targeting these sensors may offer clinical benefits in kidney disease in which oxidative stress and/or hypoxia is a final, common pathway.

Glomerulonephritis is one of the commonest causes of end-stage renal failure worldwide. Although there have been considerable advances in the management of renal failure by dialysis and transplantation, there has been relatively little progress in its prevention. This volume sets out to review current practice in the treatment of glomerulonephritis, which is aimed both at controlling the clinical manifestations, e.g. nephrotic syndrome, and at preventing the progression to renal failure. The term glomerulonephritis covers a wide range of conditions with different immunological, histological and clinical features. This volume therefore starts with reviews of the immunology and pathology of different types of glomerulonephritis. This is followed by detailed consideration of the treatment of the commoner primary and secondary forms of the disease. There are separate chapters on special circumstances, such as glomerulonephritis in pregnancy or following renal transplantation. In each chapter, attempts are made to review the evidence for the effectiveness of treatment, based on controlled trials, immunopathological principles and the authors' considerable experience. Although some aspects of the treatment of glomerulonephritis can be found in the standard texts on renal disease, this volume provides an up-to-date, thoroughly referenced, and practical guide to management. As such, it should be of value to nephrologists and general physicians, including those in training, and to postgraduate students of nephrology.

aintaining extracellular calcium concentrations within a narrow range is critical for the survival of most vertebrates. PTH, together with vitamin D, responds to hypocalcemia to increase extracellu M lar calcium levels, by acting on bone, kidney and intestine. The recent intro duction of PTH as a major therapeutic agent in osteoporosis has directed renewed interest in this important hormone and in the physiology of the parathyroid gland. The parathyroid is unique in that low serum calcium stimulates PTH secretion. As hypocalcemia persists, there is also an increase in PTH synthesis. Chronic hypocalcemia leads to hypertrophy and hyper plasia of the parathyroid gland together with increased production of the hormone. Phosphate is also a key modulator of PTH secretion, gene expres sion and parathyroid cell proliferation. Understanding the biology of the parathyroid as well as the mecha nisms of associated diseases has taken great strides in recent years. This book summarizes the molecular mechanisms involved in the function of the para thyroid gland. The first chapter reviews the development of the parathyroid gland and the genes involved in this process as identified using genetically manipulated mice. Then the biosynthetic pathway of PTH from gene ex pression to its intracellular processing and the sequences in the gene control ling its transcription as well as those regulating mRNA processing, stability and translation are described."

More than half a million people worldwide are now sustained by renal replacement therapy, mainly hemodialysis at a cost exceeding USD 30 billion per year. Each case of ESRD that is delayed or prevented saves funds that may be applied to other aspects of health care. Edited by an internationally renowned nephrologist, Prognosis for Kidney Disorders provides a timely summary of exciting work in progress directed toward renoprotection and of ultimate interdiction of ESRD.
Suitable for researchers and clinicians, Dr. Morrell Michael Avram has collected and commented on promising initiatives likely to enter everyday practice in the immediate future. Suitable for renal trainees, experienced kidney doctors, nurses, nutritionists and cardiologists.

Is the nephrology community facilitating excess cardiovascular deaths in patients with kidney failure and anemia by treating to a subnormal hematocrit? Why have clinicians and nephrologists permitted health insurance companies and the government to decide when anemia therapy should begin in persons with progressive kidney failure? Is iron the only variable that can be manipulated to maximize response to recombinant erythropoietin? Are we using too much intravenous iron in kidney failure patients, and is oral iron supplementation worthless in sustaining iron stores during long-term erythropoietin treatment? When does left ventricular hypertrophy begin to emerge in patients with progressive renal disease and is there convincing evidence that anemia is a significant cause of LVH in this setting? Is darbepoetin alfa, a new novel, long-acting erythropoietin, really superior to recombinant erythropoietin? This book is a compilation of proceedings from a conference in Brooklyn convened to address these and other controversial and unresolved issues in renal anemia management.

Clinical Management of Renal Transplantation presents The Belfast City and University Hospital experience in renal transplantation. Over the years, the Belfast Renal Transplant Unit has acquired considerable experience in all aspects of renal transplantation which have led to excellent results. The team working in the Belfast Renal Transplant Unit has built up an outstanding reputation which has become widely known. This volume is a comprehensive, practical reference work for senior medical students and nurses as well as for the established nephrologist and transplantation surgeon. It provides a clear and concise picture of the care needed by patients who are being prepared for renal transplantation or who have recently received a kidney transplant.

Ethical rational, facts, and center techniques for choosing kidney donors all in one volume. This is the first book of its kind, devoted solely to preoperative issues for living kidney donors and those who counsel them. The eight chapters are devoted to vital areas that are comprehensively addressed by experienced professionals. The book presents a unified ethical and factual approach that is essential for all transplant centers to understand. It is a readable and understandable ethical foundation for living kidney donation that is free of jargon. It includes balanced, hard to find factual summaries that are essential for acceptable kidney donor counseling. As transplant centers increasingly turn to living kidney donors, this book is an essential step forward in the field.
The book will appeal to transplant physicians and surgeons, transplant coordinators and social workers, nephrologists who have patients on dialysis or who evaluate potential living kidney donors and to potential living kidney donors and their recipients. As a practical application of medical ethics to an important field, it will be of interest to medical ethicists as well.

Cardiovascular complications are not only responsible for more than half of our patients' mortality, they also represent the bulk of everyday problems in a dialysis unit. Yet, the space allocated to them in the major textbooks covers only 2-8% of their total content. The origins of this book lie in many years of day-to-day care of dialysis patients. It gradually became clear to the author that systematic application of well-known pathophysiological principles could improve patients' conditions beyond expectations. More importantly, it appeared that world literature was mainly concerned with evaluating risk factors and that efforts to improve prognosis were concentrated on urea removal. It is important, therefore, to notice that Volume Control', the central issue of this book, is not incorporated into the Adequacy' concept. While primarily intended for dialysis doctors, the author sincerely hopes that dialysis nurses, who carry the lion's share of day-to-day responsibility for dialysis patients, will also find this book a useful and practical guide to dialysis treatment.

The aquaporin field has matured at an exceptionally fast pace and we are at the verge to develop serious strategies to therapeutically modulate aquaporin function directly or via regulatory networks. Key prerequisites are available today: i. a considerable (and growing) number of aquaporin crystal structures for the rational design of inhibitory molecules, ii. elaborate molecular dynamics simulation techniques for theoretical analyses of selectivity mechanisms and docking experiments, iii. comprehensive data on aquaporin immunohistochemistry, iv. aquaporin knockout animals for physiological studies, and v. assay systems for compound library screenings. The structure of this volume on aquaporins follows the points laid out above and thus covers the developments from basic research to potential pharmacological use. Situated between pharmacology textbooks and recent scientific papers this book provides a timely overview for readers from the fundamental as well as the applied disciplines.