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."

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.

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 first edition of this book was well received by updated. The two of us have made further collab orative efforts to present a better understanding of medical students, graduate students, and clinicians interested in furthering their understanding of basic the function of the kidney in conjunction with the principles of renal physiology. Most of the reviews most recent anatomical findings. of the first edition and comments from the various The second edition consists of 13 Chapters and 3 instructors who used the book were very positive Appendices. As in the first edition, the anatomical and complimentary with regard to the presentation description of the kidney is incorporated into the of the physiological information and the use of the various chapters dealing with kidney functions. Most system analysis approach to describe renal function. of the anatomical information was written by Wil These positive and encouraging comments over the helm Kriz. The physiological information was writ past nine years, since the publication of the first ten by Esmail Koushanpour, except for Chapter 12 edition, gave us the impetus to consider the prepa which was jointly written. Chapters 1 through 3 were ration of a second edition."

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."

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.

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.

In one golden age of medicine epitomized by William Osler, the physician also aspired to mastery of gross and microscopic pathologic anatomy. Now another such age has dawned in which ultrastructure and immunopathology provide insights into mysterious diseases of the kidney, connective tissues, joints, and muscles, among other sites. Dr. Anil K. MandaI has a background in clinical nephrology, experimental pathology, and diagnostic pathology of renal diseases that suits him well for his chosen task. This is to explain clearly the clinicopathologic entities seen by nephrologists, using the full range of available morphologic techniques. His ap- proach is brisk and incisive. To read his monograph as a pathologist is to make oneself a better clinician, and as a physician is to improve one's grasp of pa- thology. Such correlative knowledge seems at present the means most likely to lead to the ultimate control of some crippling chronic renal diseases. Sheldon C. Sommers, M.D.

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."

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.

Organ Shortage: The Solutions is the latest subject in the Continuing Education series, organized by Fondation Marcel Merieux and Universite Claude Bernard in Lyon. The annual subject is chosen to reflect the status of the topical issues of the year, as taught by leading international experts. The contribution of transplantation and clinical immunology to advanced medicine is considerable and promising. The annual volumes in this series keep the reader abreast of these developments. "

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.

For the last two decades, the topic of chronic renal failure has been dominated by discussions on dialysis and transplantation. As facilities for treating patients with end-stage renal failure have become more readily available, at least in Europe and North America, attention has once again been drawn to conservative measures which may improve both the overall prognosis and the quality of life of patients with renal impairment. Although severe renal failure may be progressive and many patients will ultimately require some form of renal replacement therapy, it is now widely appreciated that distressing symptoms can often be ameliorated by judicious medical treatment. Children as well as, and perhaps to a greater extent than, adults may benefit from such therapy. This volume examines relevant trends in the conservative man agement of both adults and children with chronic renal failure. Each chapter has been written by recognized experts and provides infor mation of clinical relevance for the average clinician. As the overall prognosis for patients with end-stage renal failure improves it is clear the management of patients with relatively stable chronic renal failure is an important topic not only for nephrologists but for all practising clinicians."

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.

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."

Nephrology, initially born as a small branch of medicine, has, in the last few decades, become an extraordinary large field of medicine. The recent development of renal medicine is mirrored by the numerous nephrological journals published, a natural consequence of the increasing number of basic and clinical research studies performed continuously all over the world. Undoubtedly the progress which has occurred in the different, specific fields of renal medicine has given rise to subspecialities which range from renal physiology and pathology to hemo- and peritoneal dialysis and renal transplantation. Even the diagnostic methodology in nephrology, very useful in the clinical practice, has become a speciality within the speciality. Thus, the problem for clinical nephrologists, as well as for internists, is to remain continuously up-dated in all fields of nephrology. Nephrology textbooks are published continuously and in great number. However, the time required for having authors appointed, chapters completed, manuscript edited, galley proofs corrected and the whole book printed makes many textbooks already out of date when they go on sale and their half lives are very short. On the other hand, nephrological journals are so many and the articles so numerous and detailed, that it is often impossible to rely on them for up-dating practicing clinicians.

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

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.

This volume is based on a very successful meeting on organ transplantation that was held in Kuwait in 1990 under the auspices of the Middle East Society for Organ Transplantation. An international group of organ transplant experts attended this conference and their contributions and deliberations have been recent1y updated to produce this definitive and authoritative summary of current clinic al practice in organ transplantation. The initial chapters appropriately focus on the immunology of organ trans plantation with special emphasis on the initial events in the induction of alloreactivity, the mechanisms of rejection, and the potential for tolerance induction. A strong emphasis is placed on the diagnosis of rejection by cellular analysis. The section on immunosuppression deals with several new areas of clinical therapy. The section on renal transplantation is unique in several respects, the long-term results from various countries, including the Middle East, are summarized, the use of living unrelated donors and of ABO incom patible donors - all strategies to maximize organ availability - are presented."

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.

The 1992 International Yearbook of Nephrology is the 4th in a successful series of yearly books updating practising nephrologists and nephrologists-in-training on rapidly changing areas of nephrology. We were encouraged to proceed in our editorial venture by reviews of the previous issues which have appeared in various Nephrology Journals. These reviews have pointed to the successful use of the International Editorial Board, the broad range of topics of current interest which have been covered and the comprehensive and practical nature of the reviews. The principal aim of the Yearbook remains to provide reviews which are more current than those which appear in Nephrology textbooks and which can be in the hands of the readers a few months after the authors have completed the manuscripts. The appointed authors are always experts in the field, who are asked to give an objective review of the topic, up-dating the readers on the world-wide literature and providing them with a complete, accurate and up-ta-date list of important recent references. We have decided to maintain the successful format of the first three issues. Thus, the volume will continue to be divided into sections; each section will continue to have a different primary focus every year, depending upon what is of greatest interest at the time.

Fresh insights into the pathogenic mechanisms by which hyperglycemia induces tissue and organ injurt are the basis for rapidly evolving promising therapies in diabetes. Especially promising as targets for intervention are products of oxidative stress, including kinins and growth factors. Improving results of renal replacement regimes now incorporating pancreatic islet transplants are able to delay and prevent end-organ damage in diabetic individuals. The evolving story of the taming of diabetes is of direct concern to nephrologists, endocrinologists, ophthalmologists, primary care physicians and medical students.

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.