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."

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."

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.

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 haemofiltration in the intensive therapy unit and haemoperfusion for certain types of poisoning, the basic principles of haemodialysis 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 extra corporeal 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. ABOUT THE EDITOR Dr Graeme R. D. Catto is Professor in Medicine and Therapeutics at the University of Aberdeen and Honorary Consultant Phy sician/Nephrologist to the Grampian Health Board. His current inter est in transplant immunology was stimulated as a Harkness Fellow at Harvard Medical 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."

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.

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.

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."

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."

Im Juni 1979 hatte in Dusseldorf ein Symposion uber Diuretika stattgefunden. Behandelt wurden experimentelle und klinische Ergebnisse mit Diuretika, unter anderem mit Diucomb. Ziel des Symposions war, Untersuchungsergebnisse zu referieren und diskutieren. Teilnehmer waren Wissenschaft ler aus der Schweiz, Osterreich, Grossbritannien, USA und der Bundesrepublik Deutschland. Das Material dieses Symposions wurde uberarbeitet, Diskussionen durch einen Redaktionsstab gestrafft. Wir danken Frau J. BOROS fur wertvolle technische Assistenz. Der Springer-Verlag hat uns wiederum sach kundig beraten und ist in grosszugiger Weise unseren Wunschen entgegengekommen Die Herausgeber Inhaltsverzeichnis Einleitung. F. KRUCK . . . . . . . . . . . . . 1 1. Wirkungsmechanismen. Moderation: K. GREEFF . 3 Plasma Concentrations and Comparative Bioavailability of Bemetizide and Triamterene in Combination. L. F. CHASSEAUD . . . . . . . . 5 Pharmakokinetik von Diuretika bei eingeschrankter Nierenfunktion. H. KNAUF und E. MUTSCHLER 14 Diskussion 24 Neue Daten zur Toxizitat von Diuretika. F. LEUSCHNER 26 Diskussion 29 2. Renale Wirkungen. Moderation: O. KRAuPP. . . . . . . . . . . . 33 Die Wirkungsweise diuretischer Substanzen in Abhangigkeit von ihrer re- len Behandlung. P. DEETJEN . . . . . . . . . . . . . . . . . . . 35 Effects of Diuretics on Renal Potassium and Hydrogen Ion Transport. G. GIEBISCH and M. HROPOT . . . . . . . . . . . . . . . . . . . 42 Wirkungen von Diuretika auf den transzellularen Elektrolyttransport der Niere. M. WIEDERHOLT und L. L. HANsEN 53 Diskussion 60 Interaktion zwischen Diuretika und renalem Prostaglandinsystem. H. J. KRAMER, B. STINNESBECK, W. PRIOR und R. DUSING 64 71 Diskussion Untersuchungen zum Wirkungsmechanismus von Acetazolamid und SITS auf den Bikarbonattransport im proximalen Tubulus der Rattenniere."

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.

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.

One of the time-honored foundations of the practice of pediatric medicine is the understanding and application of the principles of fluid, electrolyte and acid-base disorders. Presented in a new softcover format, "Fluid and Electrolytes in Pediatrics: A Comprehensive Handbook" brings together a select group of authors who share a passion and an appreciation of the contributions of pioneers in pediatric medicine and an expertise for their respective areas in a new softcover edition. The volume provides in-depth discussions of the basic functioning of the kidneys, skin and the lungs. Each chapter describes the etiology and demographics, biological mechanisms, patient presentation characteristics, therapy options and consequences of optimal treatment as well as delayed treatment. "Fluid and Electrolytes in Pediatrics: A Comprehensive Handbook" provides health professionals in many areas of research and practice with the most up-to-date, accessible, and well referenced volume on the importance of the maintenance of fluid and electrolyte concentrations in the pediatric population, especially under acute care.

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.

Advanced Renal Cell Carcinoma (RCC) cannot be cured by surgery alone. Its resillience to irradiation and chemotherapy demands a new approach to the management of this disease. This book provides an overview of the scientific and clinical developments of RCC, and clarifies the fields ofimmunotherapy and immunobiology. The book contains a compilation of approaches that will enhance the effectiveness of the management of advancedRCC, even in the absence of definitive pre-clinical data. These require additional study and will stimulate the reassessment of preliminary results.Furthermore, preliminary results of already implemented clinical trials withbiological modifiers are presented. Of special interest are the current achievements in the field of immunotherapy using topically and subcutaneously low dosage combinations of cytokines. This concise volume will benefit those seeking a thorough review of the research and the clinical aspects of RCC simultaneously.

The human prostate gland is of undoubted importance in reproductive physiology and is one of the commonest causes of clinical urological problems in the male patient. Despite the wealth of published lit erature relating to the prostate gland surprisingly little is understood about its neural innervation, the influence of pharmacological factors and its precise physiological functions. Indeed, benign disorders of the prostate gland including benign prostatic hyperplasia, bladder neck dyssynergia and inflammatory disorders of the prostate (prostatitis, prostatodynia) although well recognised clinically, are as yet poorly characterised and understood. It was not until the late 1960s that the subject of urodynamics, which for the first time allowed scientific assessment of the function of the lower urinary tract, was introduced. The first section of this book considers recent advances in our understanding of the innervation of the bladder and prostate gland and the changes in bladder function which accompany prostate medi ated bladder outflow obstruction. The clinical consequence of benign prostatic hyperplasia in many patients is bladder outflow obstruction and although the traditional treatment of these conditions is by the use of ablative surgery, in recent years a number of new modalities have been investigated and are reviewed in the second section of the book.

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."

After the positive response which followed the first edition of this book 6 years ago, the editors were encouraged to prepare a completely reworked second edition that includes the modern advances in this field. There has been a complete change of diagnostic procedure in the detection of renal tumors, which is now based on sonography, computed tomography, and nuclear magnetic resonance imaging, pushing intravenous urography and angiography completely into the background. Also, new methods of treat ment with radionuclides using embolisation are incorporated. The description of morphological structures forms the basis for under standing and recognising pathology of the kidneys and adrenals. The con tents of pathological morphology could be extended, as we are of the opinion that the detection and therapy of renal and adrenal tumors are derived from different areas of diagnostic science. We are indebted to Springer-Verlag for the excellent book production. On behalf of all the authors, we would like to thank our colleagues and associates for their cooperation in the realisation of this project. The editors hope that this volume will be of interest to radiologists, pa thologists, urologists, pediatrists, and also radiotherapists. Essen, April 1987 EBERHARD LOHR LUTZ-DIETRICH LEDER Table of Contents Pathology of Renal and Adrenal Neoplasms LEDER, L.-D., RICHTER, H.l.

This book includes the proceedings of the 2nd International Meeting on Cur- rent Therapy in Nephrology held in Sorrento, Italy, May 22-25, 1988. The book provides a comprehensive update on new therapeutic strategies in the broad field of Nephrology. The reader will receive information on advances in treatment of glomerulonephritis, new dialysis techniques and progress in renal transplantation. In addition, sections deal with provocative experimental ap- proaches to treating renal disease. Topics include: cyclosporine in treatment of nephrotic syndrome, plasma ex- change in ARF, treatment of beta-2 microglobulin amyloidosis, nutritional of dialytic adequacy revisited after assessment in patients on RDT, standards development of biocompatible membranes, drug interaction with cyclosporine, renal transplantation in elderly recipients, and renal transplantation with elderly donors. A special effort was made to recruit contributors among the most important scientific authorities in their respective fields: we are grateful to Drs. Cameron, Lamm, Isemberg, Meyrier, Niaudet, Brynger, Lundgren, Fauchald, Cockburn, Gotch, Kopple, Cheung and Horl for having accepted our invitation. We are also indebted to all other authors who participated in the meeting and submitted their original papers for publication. I.

The hemodynamic mechanisms of hypertension are often limited to the study of three dominant parameters: blood pressure, cardiac output and vascular resis tance. Accordingly, the development of hypertension is usually analyzed in terms of a 'struggle' between cardiac output and vascular resistance, resulting in the classical pattern of normal cardiac output and increased vascular resistance, thus indicating a reduction in the caliber of small arteries. However, during the past years, the clinical management of hypertension has largely modified these simple views. While an adequate control of blood pressure may be obtained with antihypertensive drugs, arterial complications may occur, involving mainly the coronary circulation and suggesting that several parts of the cardiovascular system are altered in hypertension. Indeed, disturbances in the arterial and the venous system had already been noticed in animal hypertension. The basic assumption in this book is that the overall cardiovascular system is involved in the mechanisms of the elevated blood pressure in patients with hypertension: not only the heart and small arteries, but also the large arteries and the venous system. For that reason, the following points are emphasized. First, the cardiovascular system in hypertension must be studied not only in terms of steady flow but also by taking into account the pulsatile components of the heart and the arterial systems. Second, arterial and venous compliances are altered in hypertension and probably reflect intrinsic alterations of the vascular wall."

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.

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."