I am honored to be invited to prepare a foreword for the proceedings of the Second International Lubeck Conference on Erythropoietin (Epo). I congratulate Wolfgang Jelkmann, Horst Pagel and Christoph Weiss for their organization of an excellent program for this conference which updated all of us on the advances made in erythropoietin research during the past few years since the first conference in June of 1988. I am sure that Professor Paul Carnot, had he been present at this conference, would be very pleased and proud of the advances made in the field of erythropoietin since his and Madame DeFlandre's seminal finding in 1906 (1) that rabbits produced a humoral substance following bleeding which controls red blood cell production. The reports by Hjort in 1936 (2) and by Erslev in 1953 (3) that large volumes of plasma or serum from rabbits following a bleeding stimulus, when injected into normal donor rabbits, produced a reticulocytosis, were very significant in confirming the existence of a humoral factor which controls erythropoiesis. Reissmann's parabiotic rat experiments in 1950 (4) reawakened interest in erythropoietin when he proved that hypoxia stimulated the production of a factor which regulates red cell produc tion. The studies of several investigators such as Jacobson et al. (5), Fisher and Birdwell (6), Kuratowska et al. (7) and Nathan et al."

The aim of the INTERNATIONAL YEARBOOKS OF NEPHROLOGY is to publish every year a volume to keep nephrologists up to date on all the rapidly changing areas of nephrology. Each volume will be published by the end of each calendar year which corresponds with the annual meeting of the American Society of Nephrology. Each issue of the INTERNATIONAL YEARBOOKS OF NEPHROLOGY will be divided into sections; each section will have different primary focus every year, depending upon what area is of greatest interest at the time. In other words, each annual volume will deal with what is truly current in nephrology. All the authors appointed for the chapters of the INTERNATIONAL YEARBOOKS OF NEPHROLOGY are known experts in the field who will give an objective review of the topic up-dating the readers on the world-wide literature. A crucial point for the success of the INTERNATIONAL YEARBOOKS OF NEPHROLOGY is the list of the references at the end of each chapter. We have asked all authors to provide a complete, accurate and up-to-date list of important references. In order to guarantee the most up-to-date yearbook, very rapid production is mandatory. Rapid publication can be obtained only with camera-ready manuscripts for direct photo-offset reproduction. Thus we have agreed to use photo-offset printing for the series. For the first issue of the series, the INTERNATIONAL YEARBOOK OF NEPHROLOGY 1989, the Editorial Board has focused attention on the latest and most important scientific and clinical advances in nephrology.

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."

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."

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."

Blood pressure control is central to all bodily functions. There are many points in the multifaceted cybernetic system wherein hypertension may be produced. Hypertension is a 'young' disorder whose existence has been known for less than a century. It is not only extremely prevalent among every popula tion, but also deleterious to the health of mankind. The more we understand about hypertension's harmful effects, the more urgent is the need for its effective control. The kidney is the central organ that controls vascular tone and body fluid volume; these two factors are dominant in determining arterial blood pres sure. Hence, it is not surprising to find in hypertensive disorders that there are abnormalities in the kidneys, functional or anatomical, subtle or overt, that cause or are the consequence of hypertension. The first suggestion that the kidney could cause hypertension was made in 1836, before arterial pressure could even be measured, by Richard Bright. He observed that cardiac hypertrophy was often present in patients who died of renal disease. It was, however, Goldblatt and his colleagues in 1934 who opened the modern era of experimental and clinical research in renal hypertension. Since then, although far from complete, enthusiastic and intensive research efforts have greatly improved our understanding of the nature of renal hypertension."

The previous volume on Antihypertensive Agents in the Handbook of Experi mental Pharmacology, published in 1977, was edited by the late Franz Gross from the Department of Pharmacology in Heidelberg, who was one of the grand old men in hypertension research. Now, more than 10 years later, it is necessary to update this volume. From the early days of antihypertensive drug treatment, starting about 30 years ago with drugs such as reserpine and guanethidine, the pharmacology of cardiovas" cular therapy has evolved into a highly sophisticated and effective therapeutic regimen. The major breakthroughs in the 1960s were the introduction of diuretics and beta-blockers. Then, in the 1980s, came the calcium antagonists and con verting enzyme inhibitors. It can be anticipated that the next decade will see a further expansion and sophistication of blood pressure lowering drugs. This book provides a state-of-the-art discussion of chemical, experimental, and clinical pharmacological data as well as of practical experience with drugs which are presently being used or which are going to be introduced on the market in the near future. The purpose of this volume is to provide a complete discussion of antihypertensive agents. Each major class of antihypertensive drugs is treated exhaustively in a separate chapter, fully referenced with chemical formulae, and richly illustrated with figures and tables. International authorities were asked to contribute in their respective fields of expertise."

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.

In recent years both doctors and patients have become increasingly aware that many essential drugs may induce unfortunate side-effects in susceptible individuals. The kidney is the principal route of excretion for many of these substances and may as a result become involved in pathological processes. Developments in haemodialysis and haemo perfusion may be of value in increasing the rate of excretion of potentially toxic substances but it is essential that the advantages and disadvantages of these techniques are fully appreciated by all with an interest in clinical practice. This book details the recent advances in understanding of analgesic nephropathy, interstitial nephritis, elimination of poisons and drug monitoring. Each chapter has been written by a recognized expert in the field and provides information of relevance and practical import ance to the average clinician. The developments of the last decade have emphasized that drug toxicity is a subject on which all clinicians, but perhaps especially nephrologists, should be fully informed. ABOUT TH E 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 Medicial School and the Peter Bent Brighton Hospital, Boston, USA. He is a member of many medical societies including the Association of Physicians of Great Britain and Ireland, the Renal Association and the Transplantation Society."

Acute renal failure is undoubtedly one of the marize in one volume the recent advances on patho- most interesting and frequent syndromes observed physiology of acute renal failure, the clinical aspects by clinicians. A great number of factors may of the various forms (even those which have been acutely impair renal function, but the pathoge- disregarded in other surveys), the diagnostic tests netic mechanism by which this occurs is fre- available today in our clinical practice, the general quently unknown. Even the pathophysiology of and specific therapeutic measures and (very impor- ischaemic!toxic forms of acute renal failure re- tant, indeed), some useful suggestions for preven- mains controversial despite the huge number of tion. experimental and clinical studies. The contributors have provided clear, complete Medical management of patients with acute renal and up-to-date chapters. I am deeply grateful to failure has greatly improved in recent years, partic- them all. ularly with the use of different types of dialytic I like to express my sincere thanks to Dr. A.J.

Concise, recent data are presented on obstetric problems arising in patients with cardiovascular diseases (not only congenital and acquired valvular heart diseases and hypertension, but also uncommon heart lesions) and on cardiological complications encountered in pregnant women. The goal of the book is to provide obstetricians with necessary cardiological information and cardiologists with essential obstetric information to enable both specialists to make optimal decisions regarding the permissibility of pregnancy, management of pregnancy and labour, or termination of pregnancy, and selection of an adequate form of contraception in women with heart and vascular diseases. Along with recent scientific findings, the book contains practical recommendations for examination diagnosis and treatment that is effective for the mother and safe for the fetus.

The renewal of interest in peritoneal dialysis as a treatment modality for patients with end-stage renal disease was stimulated by the report of Po- povich and his colleagues in 1976 on the technique of CAPD. With the in- troduction of commercial dialysate-containing plastic bags, which mark- edly reduced the incidence of peritonitis, the use of CAPD as a primary treatment modality has increased significantly. At the present time, more than 12% of the patients undergoing dialysis in the United States are utiliz- ing CAPD; however, the use of CAPD among pediatric patients is con- siderably greater. The First International Symposium on CAPD in Children was orga- nized in order to gather together experts with experience in treating chil- dren undergoing CAPD in an attempt to exchange current information on the utilization of this emerging technique in children. Since pediatric pa- tients comprise a small percentage of the CAPD population and since lim- ited data were available concerning specific methodology and complica- tions of CAPD in children, it was hoped that an international symposium would provide a forum for an exchange of experience that would ultimate- ly lead to better adaptation and increased utilization of this technique.

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.

The mechanisms by which animals regulate the volume and composition of their body fluids has long had a particular fascination for students of biology. As a consequence, the subject can lay claim to an impressive record of ground breaking scientific achievements as well as a provocative body of philosophical speculation concerning the role of the system in the origin and evolution of life. Indeed, the entire concept of homeostasis on which so much of o r current biologic thinking is based, derives from Claude Bernard's pioneering exploration of the forces that determine the composition of this 'internal sea'. Other seminal achievements credited to this area of inquiry include the first description of a genetically transmitted human disease (familial neurogenic diabetes insipidus); the first isolation sequencing and synthesis of a peptide hormone (vasopressin and oxytocin); the first demonstration of peptide hormone synthesis by way of a larger protein precursor; the first description of resistance to the biologic actions of a hormone (nephrogenic diabetes insipidus); and the conceptual realization of the unique counter-current mechanism that permits concentration of the urine. This record of far reaching and fundamental advances has been distinguished by many fruitful inter actions between clinical and basic science."

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.

Decoding the significance of proteinuria as an indicator of severity or prognosis in kidney disease is a stimulating challenge to students and practitioners of nephrology. Sir Richard Bright in 1827 associated pro with the disease that bears his name. In the subsequent more teinuria than a century and a half, however, the meaning of the linkage between proteinuria and renal disease remains elusive. Proteinuria is discovered on routine urinalysis in about 10 million Americans, most of whom express no symptoms of kidney disease, each year. From the studies of Robinson (updated in these pages), we know that proteinuria, per se, can be present for 20 years without change in re nal function, as described in orthostatic proteinuria. By contrast, pro teinuria may be the harbinger of swift kidney destruction, rarely cul minating in clinical collapse, a syndrome typifying "malignant proteinuria" as detailed herein by Avram. Although proteinuria is ubiquitous, an orderly management strategy for rational handling of proteinuria of less than nephrotic range is lack ing. Separation of tubular proteinuria and transient proteinuria of fever is now possible routinely. This book provides a record of the contribu tions of investigators and clinicians whose work forms the substrate for production of understanding and, ultimately, marching orders for prac titioners seeking optimized management for their proteinuric patients."

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.

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.

The behavior of the kidney in normal pregnancy, as well as in complicated pregnancy, is a very interesting, but still in many ways an unknown topic in renal medicine. It is undoubtedly difficult to determine, even in normal women, the behavior of renal hemodynamics throughout gestation, since the fear of impairing a new life (i.e., the fetus's life) will limit, for ethical reasons, the use or the frequent repetition of diagnostic tests on the mother. On the other hand, the study of complicated pregnancy even for diagnostic purposes (for planning adequate treatment), except in a few countries that are known for the advanced health education of the population, has to face serious difficulties. First of all, pregnant women usually seek the help of an obstetrician when gestation is already in an advanced stage. This makes it difficult to determine when and how asymptomatic signs of any disease discovered during pregnancy have first occurred. A second difficulty is that frequently the patient does not know whether a given disease has preceded pregnancy. Pregnancy is a condition of young women, and a young woman frequently has never seen a physician; thus, no urine analysis or blood tests have been performed before the gestation. Not infrequently, even blood pressure has never been measured. This will make it difficult to classify hypertension discovered in late pregnancy as pregnancy-induced hypertension or as chronic hypertension in pregnancy.

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."

Secondary forms of hypertension are not uncommon in clinical prac tice, but they are often overlooked or forgotten by clinicians in many fields of medicine. Dr. George Mansoor' s volume on Secondary Hyper tension is an important contribution to the field of clinical hypertension and vascular diseases, since it brings up to date the numerous diagnostic and therapeutic advances in the evaluation for secondary types of hyper tension. In the past, textbooks usually stated that an etiology could be determined in less than 5% of patients presenting with newly diagnosed hypertension. We now know this is far too low a proportion (e.g., pri mary hyperaldosteronism alone may account for hypertension in 5% of patients presenting with chronic elevations in blood pressure). Secondary Hypertension has been thoughtfully organized into chap ters evaluating screening and diagnosis, as well as medical and/or sur gical intervention of the well-known etiologies of secondary hypertension in adults and children. Additional coverage is given to such exogenous or lesser appreciated causes of secondary hypertension as obstructive sleep apnea and drugs. These sections make this book novel because in the past little attention has been paid to the effects of noncar diac drugs that interfere with antihypertensive therapy or to exogenous substances that might induce refractory hypertension."

In examining the preface of our first book, it is increases needed. The Deming philosophy empha apparent that the editorial comments made in sizes that quality is never fully achieved: process 1994 are even more pertinent in today's cost- improvement is never ending. constrained healthcare environment than when But, what is quality? Without defining, David first written. We repeat them in part. Garvin makes the point that "in its original form, This is a time in history when the concept of quality activities were reactive and inspecti- quality is reaching new highs in terms of public oriented; today, quality related activities have awareness. Articles describing quality, CQI, qual broadened and are seen as essential for strategic ity tools, critical success factors, failures, and success" 1]. How can the broad context of quality lessons learned appear in local newspapers, trade be applied to the diverse aspects of ESRD? journals, scientific periodicals, and professional Furthermore, although far from a new concept, publications on a daily basis, yet implementation Continuous Quality Improvement (CQI) has taken of a quality system in many hospital units is its place as a dominant theme in many industries. approached with caution and the basic tenants of CQI is more broadly applicable, both in concept quality systems and CQI continue to be misunder and execution, to service as well as manufacturi- stood. based operations."

This eighth volume in the series Recent Advances in Endourology brings together the latest clinical findings regarding various endourological treatment modalities and innovative materials. World-recognized experts outline their techniques clearly and concisely to provide an updated review of state-of-the-art endourological techniques. International management of urological diseases is focused in this latest issue.